Current state-of-the-art review of nanotechnology-based therapeutics for viral pandemics: Special attention to COVID-19

Re iew A icle Ma jan Mo iei*, Lucian A. Lucia, Tomas Sáha, and Pe Sáha Cu en s a e-o - he-a e iew o nano echnology-based he apeu ics o i al pandemics: Special a en ion o COVID-19 h ps://doi.o g/10.1515/n e -2022-0515 ecei ed Oc obe 11, 2022; accep ed Janua y 16, 2023 Abs ac : O e he pas wo cen u ies, mos pandemics ha e been caused by zoono ic RNA i uses wi h high mu a ion, in ec ion, and ansmission a es. Due o he impo ance o unde s anding he i uses’ ole in es ab- lishing he la es ou b eak pandemics, we b iefly discuss hei e iology, symp oma ology, and epidemiology and hen pay close a en ion o he la es ch onic communic- able disease, SARS-CoV-2. To da e, he e a e no gene ally p o en effec i e echniques in he diagnosis, ea men , and sp ead s a egy o i al diseases, so he e is a p o ound need o disco e efficien echnologies o add ess hese issues. Nano echnology can be a p omising app oach o designing mo e unc ional and po en he apeu ics agains co ona i us disease 2019 (COVID-19)and o he i al dis- eases. Mo eo e , his e iew in ends o summa ize exam- ples o nanos uc u es ha play a ole in p e en ing, diag- nosing, and ea ing COVID-19 and be a comp ehensi e and help ul e iew by co e ing no able and i al applica- ions o nano echnology-based s a egies o imp o ing heal h and en i onmen al sani a ion. Keywo ds: i al pandemics, nano echnology, p e en ion, diagnosis, ea men Abb e ia ions Alum Aluminum hyd oxide ACE2 Angio ensin-con e ing enzyme II CDs Ca bon do s CNTs Ca bon nano ubes CTD Ca boxy- e minal domain CS Chi osan COVID-19 Co ona i us disease 2019 EWNS Enginee ed wa e nanos uc u es G G aphene GO G aphene oxide HA Hemagglu inin HSPG Hepa an sul a e p o eoglycan HEK Human emb yonic kidney HIV Human immunodeficiency i us IPC In ec ion p e en ion and con ol IAV Influenza A i us IVM I e mec in KGM Konjac glucomannan  * Co esponding au ho : Ma jan Mo iei, Cen e o Polyme Sys ems, Tomas Ba a Uni e si y in Zlín, Třída Tomáše Ba i 5678, 76001 Zlín, Czech Republic, e-mail: [email p o ec ed] Lucian A. Lucia: Depa men s o Fo es Bioma e ials, Chemis y, Campus Boxes 8005, 8204, No h Ca olina S a e Uni e si y, Raleigh, No h Ca olina 27695, Uni ed S a es o Ame ica; S a e Key Labo a o y o Bio-based Ma e ials & G een Pape making, Qilu Uni e si y o Technology/Shandong Academy o Sciences, Jinan 250353, China Tomas Sáha: Uni e si y Ins i u e, Tomas Ba a Uni e si y, Zlin 76001, Czech Republic Pe Sáha: Cen e o Polyme Sys ems, Tomas Ba a Uni e si y in Zlín, Třída Tomáše Ba i 5678, 76001 Zlín, Czech Republic; Uni e si y Ins i u e, Tomas Ba a Uni e si y, Zlin 76001, Czech Republic G aphical abs ac : Nano echnology is a p omising app oach o p e- en ing, diagnosing, and ea ing COVID-19 and ela ed i al diseases. Nano echnology Re iews 2023; 12: 20220515 Open Access. © 2023 he au ho (s), published by De G uy e . This wo k is licensed unde he C ea i e Commons A ibu ion 4.0 In e na ional License. LFIA La e al flow immunoassay LNPs Lipid NPs Mal Maleimide MERS-CoV Middle eas espi a o y synd ome co ona i us MWCNTs Mul i-walled ca bon nano ubes NP Nanopa icle NTD Amino- e minal domain HTCC N-(2-hyd oxyp opyl)-3- ime hylammo- nium chi osan chlo ide NA Neu aminidase ORFs Open eading ames PPE Pe sonal p o ec i e equipmen PF Phenol- o maldehyde PEG Poly(e hylene glycol) PEI Poly(e hyleneimine) PDMS Poly(dime hylsiloxane) PLA Poly(lac ic acid) PLGA Poly(lac ic-co-glycolic) PMMA Poly(me hylme hac yla e) PP Polyp opylene PS Polys y ene PVA Poly( inyl alcohol) PVDF Poly( inylidene fluo ide) RBD Recep o -binding domain Rha(s)Rhamnolipids RT-PCR Re e se ansc ip ion polyme ase chain eac ion SARS Se e e acu e espi a o y synd ome SARS-CoV Se e e acu e espi a o y synd ome co ona i us SA Sialic acid ssRNA Single-s anded RNA SERS Su ace-enhanced Raman sca e ing TMB Te ame hylbenzidine UV Ul a iole UTR Un ansla ed egion 1 In oduc ion A pandemic is an epidemic in which he ec o con agion sp eads globally. Despi e echnological de elopmen s, pandemics ha e been p e alen du ing he las wo cen- u ies. Excep o he six h chole a pandemic (1910–1911) ha o igina ed by a bac e ium (Vib io chole a), mos pan- demics ha e been caused by zoono ic RNA i uses [1]. These RNA i uses demons a e high pandemic po en ial owing o he lack o a p oo eade . The e o e, hey show highe mu a ion a es han he DNA a ie ies and a e Table 1: Diffe en i us pandemics ha ha e sp ead globally and con inue o his day (since 1918) Pandemic Vi us Yea s o ac i i y Coun y o o igin Animal ec o Global mo ali y a e (in millions) A e age mo ali y age Spanish Flu A/H1N1 1918–1920 Spain A ian 50 Ve y young, elde ly, and heal hy young adul s aged 20–40 Asian Flu A/H2N2 1956–1958 China A ian 1–2 School-age child en and young adul s aged 35–40 Hong Kong Flu A/H3N2 1968–1970 Hong Kong A ian 0.5–262–65 AIDS HIV/AIDS 1981–P esen Democ a ic Republic o he Congo Chimpanzee 36 Males abou 50.8 yea s, and emales abou 49.7 yea s epo ed in 2013. h p://www.cdc.go /nchs/da a_access/ i als a sonline.h m. Swine Flu A/H1N1 2009–2010 Mexico Pigs 0.148–0.249 37 COVID-19 SARS- CoV-2 2019–P esen China Ba s, pangolins? 5.7 h ough Feb ua y 2022 0.02% in age o 20–49, 0.5% age o 50–69, and g ea e han 5.4% in age o mo e han 80 2Ma jan Mo iei e al. mo e adap able o human in ec ion and ansmission. The o he conce ning si ua ion is sp eading h ough espi a- o y d ople s, which ansmi om pe son o pe son h ough close in e ac ions [2]. Acco ding o Table 1, mos o hese pandemics a e a ibu ed o con agious espi a o y illnesses induced by influenza i uses and co ona i uses, while he o he is an acqui ed immunodeficiency synd ome (AIDS) caused by human immunodeficiency i us (HIV)affec ing he ep oduc i e ac , heu ina y ac ,and hediges i e ac (o al ca i y, anus, and ec um). He ein, we b ieflycom- pa e hese h ee zoono ic RNA i uses epidemiologically and hen ocus on a ious s a egies o p e en , diagnose, and ea he la es ch onic communicable disease, which can also be applicable in o he i us-induced diseases. 1.1 AIDS The i us causing HIV belongs o he Re o i idae amily wi h a diame e ∼100 nm. Two majo ypes o HIV a e: HIV-1( he mos common and esponsible o o e 95% o all in ec ions)and HIV-2( ela i ely uncommon and less in ec ious). The sphe ical HIV-1 i ion con ains wo copies o (+)ssRNA genome and eplica i e enzymes su - ounded by a memb ane con aining HIV-1 en elope gly- cop o ein (Figu e 1a). This sole an igen is a homo ime ic p o ein pos - ansla ionally clea ed in o gp41, he ans- memb ane domain ha cons i u es he p o ein’s usion pep ide, and gp120, a su ace domain ha media es ecep o binding [3]. The binding o HIV-1 en elope glycop o ein o he CD4 + T cells induces con o ma ional changes in he glycop o ein and subsequen in e ac ion wi h chemokine co- ecep o s such as CCR5 and CXCR4 o acili a e ac i e anspo p ocesses. A e wa ds, in he p esence o enzyma ic machine y, RNA ans o ms in o DNA in he hos cell’s cy oplasm and subsequen ly in e- g a es in o he cell genome. Consequen ly, ch onic dis- ease is a esul o s ong an ibody esponses, which can p og ess o AIDS [4,5]. HIV ansmission mechanism: Di ec con ac o he in ec ed pa ien ’s biofluids (i.e., blood, b eas milk, male and emale sexual fluids)wi h he specific mucosa o bloods eam o he o he pe son lead o HIV-1 ansmis- sion [4]. The e o e, ansmission mechanisms a e ca e- go ized acco ding o h ee ou es: sexual, pa en e al, and e ical. Sexual ansmission occu s wi h a high con- cen a ion o HIV-1 in he geni al ac wi h a highe ansmission isk o emales [6]. Pa en e al ansmission occu s a e biofluids’con ac subcu aneously, in amus- cula ly, o in a enously [7]. Finally, e ical ansmis- sion is defined as mo he - o-child- ansmission, which occu s ia h ee diffe en ou es, including u e o, in a- pa um, and b eas eeding [8]. HIV symp oma ology: The symp oms appea as an acu e in ec ion wi hin he fi s wo mon hs and ch onic in ec ion ollowing he nex six mon hs. In he acu e phase, in ec ed people p esen swollen lymph nodes, e e , headache, ashes, and pains in he muscles, h oa , and mou h. In he ch onic phase, immunosupp ession happens, and AIDS, wi h many li e- h ea ening diseases, occu s in an un ea ed in ec ion [4]. Figu e 1: Schema ic ep esen a ion showing he s uc u e o : (a)HIV, (b)IAVs, and (c)SARS-CoV-2. SARS-COV-2 and nano echnology 3 HIV he apeu ics and ea men : Ap ima acie ea men goal is o limi i al ansmission by educing he i al load in biofluids. The apeu ic accina ion is he mos cos -effec i e, non-in asi e, p omising s a egy o long-las ing immuni y [9]. Passi e an ibody adminis a- ion, la ency e e sal agen s, adju an s, and immune modula o s a e known o enhance accine po ency [10]. His one deace ylase inhibi o omidepsin [11], wo majo ca ego ies o In eg ase Inhibi o s, and single d ug mole- cule wi h dual inhibi o ac i i y agains in eg ase and e e se ansc ip ase a e among a sui e o p omising he - apeu ics [8]. 1.2 Influenza (Flu) Influenza i uses wi h A, B, C, and D sub ypes belong o he O homyxo i idae amily. They possess ∼150–200 nm diame e s wi h oughly sphe ical o pleomo phic and fila- men ous shapes. The en elope is a hos -de i ed lipid bilaye , whe e he spikes a e adia ed ou wa d [12]. They ha e se en o eigh (−)ssRNA genome encoding s uc u al and non-s uc u al p o eins. Influenza A i uses (IAVs)a e he only ones wi h a pandemic po en ial (Table 1).IAVs ha e eigh single-s anded i al RNA segmen s in sepa a e i al ibonucleop o ein (RNP)complexes packaged in o a single i us pa icle (Figu e 1b). The s uc u e o i al RNA plays an essen ial ole in di ec ing gene easso men be ween human IAVs and animal ese oi s, which led o he eme gence o pandemic sub ypes [13]. The e a e diffe en IVAs based on he od-shaped spikes o hemag- glu inin (HA)and mush oom-shaped spikes o neu amini- dase (NA). HAs encoded by 1–16 genes and NAs encoded by 1–9 genes a e in ol ed in i al a achmen and elease, which happens a a ious pH and imes du ing he i us li e cycle [12]. O he 144 o al combina o ial possibili ies, only ou combina ions o HAs and NAs (H1N1, H2N2, H3N2, and possibly H3N8)cause pandemics owing o pa - ial o lacking immuni y in he human genome [1]. T ansmission mechanism: The mos impo an ou es o IVA ansmission a e ia con ac (i.e., di ec , indi ec , and d ople ), ai , o a combina ion. Di ec con ac occu s ia di ec physical con ac be ween an in ec ed pa ien and a suscep- ible hos ). Indi ec con ac occu s by passi e ans e o IVA o a suscep ible hos ia con amina ed hands, ins umen s, o o he in e media e objec s. La ge d ople s (≥5µm diame e ) gene a ed om he espi a o y ac o a colonized indi idual is he o he way o con ac ansmission. Finally, ai bo ne ansmission ia ae osols can occu o e ai bo ne pa icles less han 5 µm o dus pa icles con aining IVA [14]. Symp oma ology: Typical uppe espi a o y ac in ec ion symp oms include e e and chills, nonp oduc- i e cough, hini is, muscle pain, and so e h oa . In mos people, hese symp oms, excep cough and malaise, esol e a e 3–7 days, which can con inue o mo e han 2 weeks, p ima ily in elde and ch onic lung in ec ed indi iduals. In se e e disease, o i is media, espi a o y, ca diac, musculos- kele al, and neu ologic complica ions may occu [15]. Influenza he apeu ics and ea men : The main ea men goal educ ion o he i al load by diminishing i al eplica ion. The ea men is ini ia ed by p esc ip- ion o NA inhibi o s (osel ami i )plus fib a es ( enofi- b a e). Due o i us NA mu a ions, Fludase (a ecombi- nan sialidase usion p o ein), Ni azoxanide (a no el hiazolide ha inhibi s IVA eplica ion), and Fa ipi a i may co e esis an influenza s ains. Co icos e oids a e he o he common d ug, which may no be ideal o influ- enza i al in ec ions [16]. 1.3 Se e e acu e espi a o y synd ome (SARS) The li e- h ea ening espi a o y in ec ion, SARS, is d i en by an impo an species o he Co ona i idae amily, SARS-associa ed co ona i us. The ou gene a o hese co ona i uses a e alpha,be a,del a, and gamma [17]. While alpha and be a o igina e om mammals, in pa i- cula pa icula ly ba s, gamma and del a o igina e om pigs and bi ds [18]. The en eloped (+)ssRNA i uses encode s uc u al and non-s uc u al p o eins. P o eins o he memb ane, spike, en elope, and nucleocapsid a e he ou main s uc u al p o eins [1]. Among he se en sub ypes ha in ec humans, alpha‐co ona i uses (i.e., HCoV-229E and HCoV-OC43)cause asymp oma ic o mildly symp oma ic in ec ions [1,18].Whe easbe a-co ona i us subgenuses lead o diseases wi h a ying deg ees o in ec- ious po en ial, including lowe espi a o y ac in ec ion h ough HCoV-NL63 and HCoV-HKU1, se e e pneumonia h ough SARS-CoV, middle eas espi a o y synd ome co - ona i us (MERS-CoV),andfinally SARS-CoV-2[1]. Table 2 desc ibes he epidemiological cha ac e is ics o SARS in ec ions. In ec ious b onchi is i us is a gamma- co ona i us ha p oduces highly con agious disease in chickens, especially in he ep oduc i e and uppe espi a- o y ac s [17]. Howe e , diffe en del a-co ona i us spe- cies ha e no caused disease in wild bi ds; a sickness in a med quail in Poland and psi acine p o en icula dila a ion disease in g een-cheeked Amazon pa o a e a ibu ed o del a-co ona i us [19]. He ein, we ocus on 4Ma jan Mo iei e al. SARS-CoV-2 p ope ies, ansmission mechanisms, and symp oma ologies. 1.3.1 SARS-CoV-2 This subgenus o be a-co ona i us shows a high sequence iden i y as a Ba be a-co ona i us [4,17].The i ionsizeis a ound 70−90 nm, whose comple e genomic sequence shows a high gene ic simila i y wi h o he sub ypes indu- cing espi a o y in ec ions [4]. The genome is encapsu- la ed by a p o ein-based capsid co e ed by a phospholipid bilaye memb ane (Figu e 1c). The memb ane is essen ial o i us-cell usion h ough he binding o he spike p o- ein and cellula angio ensin-con e ing enzyme II (ACE2) o he a ge issues (i.e., lung, ca dio ascula sys em, in es- ine, and kidney)[20]. A e eleasing he i al genome con- aining 6–20 open eading ames (ORFs)in o he hos cy o- plasm, ORF1a/b is ansla ed in o wo s uc u al and 16 non- s uc u al p o eins o assemble in o eplica ion– ansc ip- ion complexes. The complexes wi hin double-memb ane esicles syn hesize se s o genomic and subgenomic RNAs ha encode se e al s uc u al and accesso y p o eins. The newly o med RNAs, nucleocapsid, and en elope p o eins bud om he endoplasmic e iculum-Golgi appa a us and me ge wi h he cell memb ane o o m new i al pa icles [4]. The i uses ha e demons a ed diffe en mu a ions, especially on spike p o ein, which led o u he a ian s wi h diffe en ansmission a es, ein ec ion isk, disease se e i y, and ea men [21]. This ime ic glycop o ein con- ains wodomainso S1andS2.TheexposedS1domainisin amo e a iablemode han hepa iallybu iedS2domain. The main pa s o S1 also include he ecep o -binding domain (RBD),amino- e minal domain (NTD),andca - boxy- e minal domain (CTD), which he RBD and he NTD show mo e a iabili y han CTD [21]. The a iabili y leads o many a ian s, as desc ibed in Table 3. Acco ding o he WHO, in Ap il 2022, del a and omic on a e ca ego ized in a ian s o conce n, and he o he s as a ian s o in e es . SARS-CoV-2 ansmission mechanism: I may be ans e ed di ec ly by human biofluids and indi ec ly by he en i onmen (i.e., wa e s, oods, and many su aces) [4,37]. The p ima y ansmissionme hodsa e h oughae o- sols wi h a pa icle diame e o <5µm du ing espi a ion, ocalism, o he solid esidual pa icles a e he d ople apo iza ion [38]. The e is no epo on SARS-CoV-2in ec- ion ansmission ia ood, bu i should be men ioned ha CoVs may su i e a 4°C up o 2–4dayson esh ood[39]. Acco ding o WHO, he isk o ecal ansmission seems o be low. Howe e , eces may be a eason o hands, wa e , ood con amina ions [40], and co ona i us disease 2019 (COVID-19) ansmission h ough ecal–o al, ecal– omi e, o ecal–ae osol [41,42]. SARS-CoV-2 symp oma ology: Mos cases e eal mild symp oms such as e e , cough, dyspnea, dia hea, and abdominal pain 2–14 days a e exposu e. None heless, mos se e e cases show p og essi e espi a o y ailu e and e en dea h [4]. 2 Nano echnology o p e en ion, diagnosis, and ea men In ec ion p e en ion and con ol (IPC) elies on a ho - ough unde s anding o he ac o s ha affec ansmis- sion [43]. To implemen IPC, nano echnology is a disci- pline ha offe s scien ific and p ac ical app oaches o he p e en ion, diagnosis, and ea men o in ec ious ill- nesses. In he case o p e en ion, nano-sized accines mimic he i us wi hou any eplica ed genome, eplace- able nanopo ous memb ane o N95 ace masks, applying sel -disin ec ing nanocoa ings o ai fil e s, and using nano-disin ec an s in he en i onmen a e examples o nano echnology in he p e en ion o i us sp ead [44]. Nanodiagnos ics also ely on combining nanopa icles (NPs)wi h a ge molecules o p oduce a measu able signal o de ec ion. In his echnology, he nanoscale Table 2: The epidemiological cha ac e is ics o SARS in ec ions SARS-CoV epidemic MERS-CoV epidemic SARS-CoV-2 pandemic Common symp oms Influenza-like synd ome wi h d y cough, e e , malaise, body aches and pains, dia hea Cough, e e , b ea hlessness, and e en gas oin es inal issues Cough, e e , b ea hlessness, loss o as e o smell, po en ial gas oin es inal issues Yea s 2002–2003 2015–p esen 2019–p esen Po en ial animal ese oi s Ba s Ba s Ba s, pangolins In e media y hos s Palm ci e s D omeda y camels No iden ified ye O igin Guangdong p o ince (China)Jeddah (Saudi A abia)Wuhan (China) SARS-COV-2 and nano echnology 5 Table 3: Diffe en SARS-CoV-2 mu a ions and a ia ions along wi h hei epidemiology Va ian Lineage O igin Da e Mu a ions T ansmissibili y Se e i y Re . Epsilon B.1.427 Cali o nia Ma ch 2020 Spike mu a ions: RBD, NTD, CTD, signal pep ide 18.6–24% mo e han he wild- ype s ains No e idence [22] B.1.429 Ze a P.2 (B.1.1.28.2)B azil Ap il 2020 Spike mu a ions: RBD, CTD Inc ease 23% No e idence [23] Be a B.1.351 Sou h A ica May 2020 Spike mu a ions: RBD, NTD dele ion 50% mo e han he p e iously ci cula ing a ian s High [24] Alpha B.1.1.7 UK Sep embe 2020 Spike mu a ions: RBD, NTD dele ions Highes wi h a 50–100% ep oduc ion a e High wi h 50% inc eased mo ali y [25,26] Non-spike mu a ions: nucleocapsid, p6:Δ106–108, Del a B.1.617.2 India Oc obe 2020 Spike mu a ions: RBD, NTD, CTD, S2, p oximal u in clea age si e Mo e han he alpha High [27,28] Non-spike mu a ions: o 3, o 7a, o 1a/b, and Nucleocapsid gene Kappa B.1.167.1 India Oc obe 2020 Spike mu a ions: RBD, NTD, S2, p oximal u in clea age si e High bu less han del a No e idence [29] Non-spike mu a ions: o 3, o 7a, o 1a/b, Nucleocapsid gene Gamma P.1 (B.1.1.28.1)B azil No embe 2020 Spike mu a ions: RBD, Fi e NTD mu a ions High High [30] Io a B.1.526 New Yo k No embe 2020 Spike mu a ions: RBD, NTD, CTD, signal pep ide, Nea he u in clea age si e High High [31] Non-spike mu a ions: T85I, L438P, 9 bp dele ion Δ106- 108, P323L, Q88H, Q57H, P199L and M234I E a B.1.525 Nige ia Decembe 2020 Spike mu a ions: RBD Lowe han Alpha a ian High [32] Lambda C.37 Pe u Decembe 2020 Spike mu a ions: RBD, NTD dele ion No e idence No e idence [33] The a P.3 Philippines Janua y 2021 Spike mu a ions: RBD, NTD dele ion, CTD High No e idence [34] Mu B.1.621 Colombia Janua y 2021 Spike p o ein: RBD, NTD, CTD, S2 egion High No e idence [35] Omic on B.1.1.529 Mul iple coun ies No embe 2021 Spike mu a ions: RBD, NTD, CTD, usion pep ide, hep ad epea 1, p oximal o he S1/S2 clea age si e, S2 p o ein High Low [36] 6Ma jan Mo iei e al. p ocedu es lead o handheld de ices ha a e s able, highly sensi i e, and ma ke able [44,45]. Finally, nano- echnology-based app oaches can be a p omising ool o enhance he po ency and selec i i y o physical, che- mical, and biological he apies wi h minimized oxici y o no mal cells. Ta ge ed NPs ha e been designed o deli e le hal doses o he apeu ics ac i ely o passi ely o pa ho- genic cells [46]. This nano echnology in COVID-19 mainly ocuses on dis up ing he cell ecep o ACE2 in e ac ion h ough diffe en app oaches, including ecombinan ACE2, an ibodies, and p o ease inhibi o s o sca enge he i us, in e e ing wi h he spike/ACE2 in e ac ion, and inhibi he spike p o ein p ocessing, espec i ely [20]. 2.1 P e en ion The SARS-CoV-2 i ion is p ima ily ansmi ed by ai sp eading o he en i e espi a o y sys em o he human body. A e wa ds, he i ion is unc ionally la ge due o he p esence o o he ai way ma e ials (i.e., bac e ial cells and epi helial cells)in he liquid d ople s o he espi a- o y ac . The la ge d ople s (>150 µm)show a low e a- po a ion a e, which affec s he ae osolized i us su - i al, anspo , and a e. This i ion is s able a RT and 4°C bu inac i a ed unde ul a iole (UV)ligh and ex eme pH condi ions (pH >12 and pH <3), and hea ing a 65°C o 5 min [20]. Conside ing ansmission, COVID-19 sp eading should be con olled pe sonally and en i on- men ally. Acco ding o Figu e 2, main aining accina ion, pe sonal p o ec i e equipmen (PPE), and en i onmen al sani a ion a e p ac ical ways ha lead o widesp ead com- muni y-le el p o ec ion [47]. This sec ion ou lines he po en ial applica ions o nano echnology o educing in ec- ion isks o people, wi h a specific ocusonse e alindi i- dual and en i onmen al ac o s. Recen s udies using NPs o in ec ion p e en ion a e shown in Table 4. 2.1.1 Vaccines Despi e a leng hy and complica ed accina ion p ocedu e in esol ing he pandemic ou b eak, i is highly effec i e. An effec i e accine is composed o an igens, adju an s, immune enhance s, and deli e y sys ems, which ac i- a es he immune sys em by gene a ing neu alizing an i- bodies and T cells [48]. Many ials ha e been done o de elop an effec i e accine ha a ge s ull-leng h spike p o ein o RBDs [49]. Cu en ly, con en ional accine p oduc ion pla o ms include inac i a ed i us, li e-a e- nua ed, subuni -based, i al ec o -based, and DNA/mRNA accines [47,49]. Al hough inac i a ed and li e-a enua ed accines ha e a apid manu ac u ing p ocess, he li e-a e- nua ed accine is inna ely immunogenic by affec ing he oll-like ecep o s and may eco e i ulence. None heless, inac i a ed accines a e mo e s able and sa e han li e- a enua ed accines; he an igens may be des oyed du ing inac i a ion [43,47].Beijing-based Sino ac Bio- ech (NCT04383574, NCT04352608)is one o he g oups ha de eloped he inac i a ed accines [20]. Subuni accines a e ecombinan spike p o eins wi h low immunogenici y, Figu e 2: Schema ic illus a ion o in ec ion p e en ion agains COVID-19. SARS-COV-2 and nano echnology 7 immunological memo y, and s abili y bu high sa e y and low side effec s [47,49]. Adju an s migh be added o inc ease immunogenici y and educe he numbe o accine ca gos pe dose [49]. No a ax (NCT04368988)de eloped a subuni accine con aining an adju an named saponin-based Ma ix M[20]. Vi al ec o -,DNA-,andRNA-based accines a e gene deli e y sys ems o igge a igo ous immune esponse. Due o hei in insic adju an ac i i y, non- eplicable i al ec o s ha e a s ong immune-s imula ing effec [49]. The Uni e si y o Ox o d/As aZeneca is one o he g oups ha de eloped adeno i al ec o accines o p oduce he SARS-CoV-2 spike p o ein [20]. Ano he membe o he gene ic accine is he DNA accine. Howe e , he syn he ic DNA accine is he mos able and shows lowe i e s o an ibodies han o he accina ion s a egies, and i al genome in eg a ion in o he hos DNA may lead o cance . A DNA plasmid accine de eloped by Ino io Pha maceu- icals (INO-4800)is cu en ly unde going human Phase I es ing (NCT04336410)[20]. The RNA accine con ains mRNAs o siRNAs ha swi ch offc ucial a ge genes o syn hesize i al i us p o eins [20]. Howe e , effec i e RNA deli e y o he a ge is challenging because o he he mo- sensi i i y o RNA, inse ional mu agenesis isk, and an i- ec o immuni y [47]; hey can elici high le els o neu a- lizing mAbs and memo y B cells and b oaden he esponse o diffe en a ian s [21]. Nanoma e ials ha e al eady played key oles in ac- cine deli e y sys ems due o hei s abili y, immuni y, and deli e y [20]. The ela i ely sa e NP-based accines p esen an igens in hei o iginal o ms [50]and s imu- la e an igen-specific immune esponses e en wi hou adju an [51]. These nano accines can in insically o ex insically ac i a e he immune sys em because o unc- ionaliza ion o an igenic ca gos. Biocompa ible lipid, p o ein, polyme , ca bon-based, and ino ganic NPs can encapsula e an igenic ca go wi h high loading efficiency and imp o e pha macokine ics. Majo NP pla o ms a e lipid NPs (LNPs)and p o ein NPs. LNPs, con aining ioniz- able lipids, demons a e s ong po en ial as a gene deli e y sys em wi h high loading capaci y, ans ec ion efficiency, and endosomal escaping o s abilize and p o ec hem om deg ada ion [43]. In wo s udies, LNPs we e u ilized o mRNA deli e y o RBD [52]and ull-leng h spike p o- ein [53]. The cu en US FDA-app o ed mRNA-based LNP accines a e BNT162b2 and mRNA-1273, de eloped by Pfize /BioNTech and Mode na, espec i ely [54–56].To imp o e he eal-wo ld effec i eness o he accine, alpha- i al eplicase was added o he RNA sequences and eplaced he mRNA’s un ansla ed egion (UTR)wi h a syn he ic UTR o sel -ampli y he RNA and inc ease p o ein Table 4: A semi-exhaus i e lis o selec ed NPs o in ec ion p e en ion agains COVID-19 O ganic NPs Ino ganic NPs Ino ganic/o ganic NPs LNPs P o ein NPs Polyme NPs Ca bon-based NPs Vaccina ion mRNA o RBD/ LNPs [52], Spike p o ein/LNPs [53] Spike p o ein/ e i in [64], RBDs/ e i in [65,67], RBD/ aldolases [62,63] DNA/PLA [84]Recombinan pep ide- modified nanodiamonds [97] Spike p o ein/silica NPs [93]mRNA-1273/PEGyla ed lipids [86] PPE nano-micelles o Rha(s)[99] —Syn he ic polyme s/ oligome s [100], lico ice oo s ex ac / PVA [101] G[102], polydopamine/ GO [103] Zn [104],Cu[105], Ag NPs [106], MOFs/Cu/Zn [107],Ag nanoclus e /silica composi e [108] TiO 2 nano ubes/CS/PVA, CS/PVA, and silk/PVA [109], shellac/CuNPs [110], PVDF/PS nanofibe s/Ag/Zn coa ed co on [111] Wa e and was ewa e T ea men —— CS [112]CNTs/GO/PP [113]Cu/TiO 2 nanofibe s [114]TiO 2 /G nanohyb id ma e ials [115] Ai pu ifica ion —— PMMA/PDMS/CS [116]Lase -induced G [117], MWCNTs/PF [118] Ag NPs [119], AgNP/SiO 2 hyb id pa icles [120], Ag/ Al 2 O 3 and Cu/Al 2 O 3 [121] nano-Ag/TiO 2 /CS [122], TiO 2 /c ys al iole nanocomposi es [123], ZnO NPs/ PVA/KGM [124], nano-Ag/TiO 2 /CS [122] Su ace disin ec ion —— CS [125]—TiO 2 [126], AgNPs [127], silica [128] AgNPs/cellulose [129],Cu 2 O/ polyu e hane [130] 8Ma jan Mo iei e al. ansla ion, espec i ely [49]. The e a e also adju an - encapsula ed LNPs such as QS-21 included in he lipo- somes deco a ed wi h RBDs [57]and alum-packed on he squalene [58],whicheffec i ely ac i a es he humo al and cellula immune sys em. P o ein-based NPs a e cons uc ed h ough sel -assem- bling monome s, which a e subsequen ly co alen ly o non- co alen ly bound o i al an igens [43].Thesean igen-p e- sen ing NPs imi a e he i al s uc u e and elici po en immune esponses, which a e help ul in educing he immu- nogenici y o p o ein-based accines [59]. Popula p o- eins o accinesa e e i in[60,61]and aldolase [62,63]. Recen ly, ull-leng h spike p o ein/ e i in [64], RBDs/ e i in [65],RBD-24-me / e i in [66],andRBD/ aldolases [62,63]we e gene a ed as a possible accine agains he i us. Ma e al. conjuga ed RBD and/o hep ad epea o he 24-me e i in o induce humo al and cellula immune esponses [67]. Fe i in can sel -assemble in o oc ahed al pa icles wi h h ee- old axes and p esen mul- iple o de ed i al an igens on he pa icle su ace [68]. Scien is s ha e also designed nanome pep ide accines using a new s a egy, immunoin o ma ics, o map and iden i y epi opes in he SARS-CoV-2 p o ein sequences [69]. Sahoo e al. p edic ed SARS-CoV-2 nanome epi opes o T-cell agains class I and II o majo his ocompa ibili y complex, which may se e as sensi i e, apid, and cos effec i e accines [70]. P o ein-based NPs can also be c ea ed wi h manu ac u ed nanocomponen s wi h adju- an cha ac e is ics o induce immune esponses [20]. Na u al and syn he ic polyme s (Figu e 3)ha e also been explo ed o p epa e nano accines due o highe immunogenici y, biodeg adabili y, biocompa ibili y, and a la ge su ace a ea o a ge ing [71]. They a e specifically de eloped in local and opical medica ions by conside ing hei posi i e ze a po en ial o show highe immune s imu- la ions and lowe poly(e hylene glycol)(PEG)concen a- ion o dec ease he ba ie s [49]. These polyme ic NPs, as ca ie s o adju an s, can induce ema kable an i-inflam- ma o y, an ibody, and T-cell c oss- eac i i y esponses. Chi osan (CS)[72,73], ime hyl CS/hyalu onic acid [74], β-cyclodex in/CS [75],algina e/CS[76], dex an [77],pull- ulan [78], and inulin [79]a e examples o na u al polyme s u ilized in accine deli e y sys ems. Chi osan NPs (CSNPs) ha e been ex ensi ely s udied in accine a ea owing o hei biodeg adabili y, biocompa ibili y, lack o oxici y, and ease o shape and size p ocessing [80].Tailo -made polyme s also offe ce ain ad an ages such as ep oducibili y in che- mical, biological, mechanical, and in e acial p ope ies [71]. They a e mainly poly(lac ic-co-glycolic)(PLGA)[81],poly(ϵ- cap olac one)[82], dend ime s [83],poly(lac ic acid)(PLA) [84], polyanhyd ide [85],andPEG[86].Among hesesyn- he ic polyme s, PLGA and PLA conside majo syn he ic polyme s o mucosal an igen deli e y [87].Biopolyme s asadju an scanbeconjuga edwi h a iousan igens o Figu e 3: Few examples o na u al and syn he ic polyme s. SARS-COV-2 and nano echnology 9 po cine ep oduc i e and espi a o y synd ome i us h ough inhibi ion o p oli e a ion, s imula ion o inna e immune esponses, and inhibi ion o ROS accumula ion [194]. Va ious polyme ic compounds ha e an i i al ac i i y, which comp ises polyme leng h, hyd ophilici y, and cha ge [20]. In nucleic acid polyme s, phospho o hioa ed oligonu- cleo ides we e u ilized o inhibi he en ance o hepa i is B and hepa i is D i uses and HBsAg elease agains hepa i is B i us[214]. In polysaccha ides, nega i ely cha ged poly- me sa epe haps hemos widelys udied,whichshowa b oad-spec um an i i al effec on a a ie y o i uses. Algi- na e is an example o a nega i ely cha ged polysaccha ide ha shows an i i al ac i i y due o he cha ge and phenolic s uc u e [189]. Sul a ed compounds wi h an i i al p ope - ies, including sul a ed glyco-oligome s and glyco-polyme s [190],Fucoidan-mime ic sul a ed glycopolyme s [215],PS sul ona e, PVA sul a e, polyme hylene hyd oquinone sul o- na e, naph halene sul ona e [214], dex an sul a e [216], hepa an sul a e [190,217,218], dend i ic polyglyce ol sul a e [219],andca ageenan[190,220–222]a e a ibu ed o leng h and sul a e con en . Fo ins ance, hepa in sul a e blocks he non-specific cell su ace adso p ion by p e en ing mem- b ane usion and in e ac ion wi h i al glycop o eins [190]. Mo eo e , NPs deco a ed by hepa an sul a e p o eoglycan (HSPG)o sialic acid (SA)mimics demons a ed in i o capa- ci y o a ge mos known espi a o y i uses h ough binding o he a achmen ligand o i uses and block hei in e ac ion wi h cell memb anes [20]. Polyme s modified by SA de i a i es also exhibi ed an i i al ac i i y due o he binding o i us HA o e minal sialic acid esidues on cellula glycop o eins and glycolipids. So, Gün he e al. wo ked on glycosyla ed dend i ic polyme s wi h 3′-sialyl- lac ose and 6′-sialyllac ose and confi med ha highe alency and spacing be ween ligands esul ed in highe an i i al ac i i y [191]. Posi i ely cha ged polyme s such as CS and i s de i- a i es can also ac i a e inna e immune esponses by up egula ion o cy okines and chemokines, essen ial o p e en ing i al eplica ion. Indeed, Zheng e al. demon- s a ed ha pulmona y deli e y o CS could induce wide- sp ead immune esponses agains he H7N9 influenza i us by inc easing he numbe o mac ophages, den- d i ic cells, and inna e lymphoid cells [223]. PEG exhibi s mo e nea -neu al ζ-po en ial, and mPEG is syn hesized by he eplacemen o he CH 3 moie y o he OH g oup o PEG. Acco ding o Kyluik e al., PEGyla ion o i uses wi h sho -chain polyme s can p e en in ec ing and in ading i uses. In con as ,la gechainpolyme sp o ide supe io p o ec ion when g a ed o hos cells [224].Tope - manen ly deac i a e SARS-CoV-2, Cai e al. also epo ed apho o he malco e–shell NP made o a semiconduc ing polyme and PEG unc ionalized wi h neu alizing an ibodies [225]. The p omising ac i i y o he PEG polyme owa d i usesisdue oi swa e solubili y[226], and high PEGyla- ion o NPs may cause ex ended sys emic ci cula ion hal -li e [49]. Mo eo e , NPs made o an i i al polyme s can affec i al in ec i i y by e adica ing he i us effec i ely [20]. 2.3.2 NPs as an i i al d ug ca ie s NPs a e a ac i e con olled- elease sys ems o deli e single con en ional he apeu ics (i.e., hyd ophobic/hyd o- philic small molecules and mac omolecules)o syne gis ic deli e y o mul iple he apeu ics o he a ge . Apa om lowe ing sys emic oxici y and immunogenici y in no mal issues, NPs can offe unique cha ac e is ics o he he a- peu ics, including solubiliza ion, bioa ailabili y imp o e- men , elease p olonga ion, p o ec ion agains ha sh en i - onmen s, and a ge ing passi ely and/o ac i ely [227]. Effec i eness o passi e and ac i e a ge ing is influenced by he physical cha ac e is ics o NPs, including cha ge, hyd ophilici y, size, unc ional g oups, and he conjuga ed moie y on he su ace [228]. Ta ge ed NPs lead o highe cellula up ake in a ge cells and hen d ug elease a he si e o ac ion [227]. Se e al NPs we e p oposed as p omising d ug deli e y sys ems ca ego ized as ino ganic and o ganic NPs. The ino ganic NPs wi h an i i al p ope ies a e p o- mising d ug deli e y sys ems o he a ge si e. Chlo oquine andhyd oxychlo oquinewe eloadedon ome alNPsby Mo ad e al., who concluded ha hese nanos uc u es would be an app op ia e candida e o COVID-19 ea men [200]. Silica NPs a e he o he ino ganic NPs u ilized o he deli e y o polyphospha e. Polyphospha e was eleased g a- dually a he si e, bound o he i al RBD elec os a ically, and p e en ed u he in e ac ion be ween spike p o ein and hos ecep o [201]. LNPs, as o ganic NPs, can encapsula e mac omole- cules like mRNAs o SARS-CoV-2 supp ession. Fo apid ACE2 exp ession, which can compe e wi h endogenous ACE2 in i us supp ession, mRNA was encapsula ed in β- si os e ol-doped LNPs. The mRNA can o e come limi ed hal -li e o ecombinan ACE2 [196]. The an i i al po ency o polyme ic NPs can be enhanced by a ge ing and p olonging he con olled elease o d ugs. Ta ge ed PLGA- b-PEG-maleimide (Mal)by an Fc immunoglobulin agmen was one o he polyme ic NPs u ilized o deli e hyd ophobic i e mec in (IVM)and accumula e a he lung epi helia [198]. Nie e al. also no ed ha IAV i ions bind significan ly be e o spiky NPs wi h 5–10 nm all spikes. They p edic ed ha cellula memb ane coa ing and opog aphy ha ma ches geome y migh de elop nano-inhibi o s o SARS-CoV-2[229]. 16 Ma jan Mo iei e al. The o he s a egy o i al a ge ing and neu aliza ion is coa ing polyme NPs wi h he cell memb ane [199]o gene i- cally enginee ed cell memb anes [197,230] o mimic hos cells h ough he c i ical su ace ecep o s o i al binding. Zhang e al. syn hesized PLGA NPs co e ed by ei he cell memb ane o epi heliums o mac ophages. These NPs a e agnos ic o cu en and upcoming co ona i uses since hey a e immune o a ious i us species and mu a ions [199].In adiffe en wo k, he gene ically modified memb anes we e c ea ed by ansien ly ans ec ing human emb yonic kidney (HEK)-293 T-hACE2 cells, a e which cell memb ane-based NPs we e c ea ed ia sonica ion and ex usion [197].Rao e al. also made nano-decoys by using he cellula mem- b ane o mac ophages and HEK-293 T cells wi h a high le el o hACE2. Mo eo e , many cy okine ecep o s we e p esen on he ab ica ed NPs, which can efficien ly bind and neu- alize inflamma o y cy okines like in e leukin 6 and g anu- locy e mac ophage colony-s imula ing ac o , as well as conside ably educe immunological dys unc ion and lung damage in a mouse model o acu e pneumonia [230]. 3 Challenges and u u e pe spec i es o nano echnology Vi al pandemics ha e in oduced a global challenge o he scien ific communi y in he pas wo cen u ies. Howe e , many scien is s belie e ha nano echnology has he po en- ial o o e come hese pandemics; he e a e s ill se e al impo an challenges in high ene gy consump ion, en i on- men al sa e y, and human heal h ha should be imp o ed. Nanoma e ial ab ica ion equi es a lo o wa e and ene gy, and he chemicals used a e o en highly oxic o he en i - onmen and human heal h. Diffe en ac o s, including he p esence, concen a ion, and pH o o ganic o ino ganic ma e ials, which led o he long- e m pe sis ence o NPs in he en i onmen , a e well known as en i onmen al pollu- an s [231]. Some physiochemical p ope ies o he NPs canno bep o ec edby heimmuneandinflamma o y sys- emsandlead oimmuno oxici y,inflamma ion, and oxida- i e s ess, ollowed by se e e cellula geno oxici y and fib osis [45]. The e o e, he p ima y ask is p omo ing he concep o sa e y by design and hen pe o ming he biocom- pa ibili y and biodeg adabili y app oaches using p eclinical (in i o and in i o)and clinical s udies o a candida e he apeu ic, accine, medical de ice, o diagnos ic assay [232]. Mo eo e , hese i al pandemics equi e collec i e hough beyond e hnic on ie s and cul u al di e si y. To o e come such complica ed challenges and achie e new and c i ical scien ific solu ions, a close collabo a ion among di e se esea che s a ound he wo ld wi h complemen a y skills is equi ed [20]. Acco ding o his pe spec i e, nano- echnology is an eme ging echnology whe e scien is s om inc edibly a ious backg ounds ha e collabo a ed success- ully o imp o ing complex issues in he diagnosis, de ec- ion, and ea men o i al diseases [233].The“One Heal h” concep should be add essed in he u u e due o he in e - connec ed heal h o humans, animals, and he en i onmen . 4 Conclusions Re o i uses ha e shown he po en ial o pandemic sp ead wo ldwide by hei high con agious in ec ions, which may lead o unexpec ed and e y se ious consequences. Al hough he cu en SARS-CoV-2 pandemic highly conce ns, i is no among he mos ex eme h ea s encoun e ed by humani y because science, echnology, and inno a ion ha e enabled us o iden i y, con ol, and mi iga e i . In ac , communi y hygiene and sani a ion p ac ices, effec i e accina ion, and ea men can sho en he du a ion o a pandemic. This wo k discussed nano echnology’s po en ial as a pla o m o p e- en ing, diagnosing, and ea ing COVID-19 and any u u e pandemics. The e a e diffe en ypes o NPs p oposed as p omising ounda ions o coun e ac ing he cu en global public heal h h ea . These nanosys ems a e ca ego ized in o ino ganic NPs (me al/me al oxides, silica)and o ganic NPs (lipid, p o ein, polyme , and ca bon based)can be in insi- cally o ex insically immunogenic. Finally, he idea o “nano echnology”can assis scien is s in designing NPs o immune egula ion in accine de elopmen and he apy, in he c ea ion o quick, easy, and affo dable assays o he diagnosis o COVID-19 and en i onmen al sani iza ion. Funding in o ma ion: This wo k was suppo ed by he Minis y o Educa ion, You h and Spo s o he Czech Republic –DKRVO (RP/CPS/2022/005). Au ho con ibu ions: All au ho s ha e accep ed espon- sibili y o he en i e con en o his manusc ip and app o ed i s submission. Conflic o in e es : The au ho s s a e no conflic o in e es . Re e ences [1]Pi e J, Boi in G. Pandemics h oughou his o y. F on Mic obiol. 2021;11:3594. SARS-COV-2 and nano echnology 17 [2]Luby SP. The pandemic po en ial o Nipah i us. An i i Res. 2013;100(1):38–43. [3]Doms RW, Moo e JP. HIV-1 memb ane usion: Ta ge s o oppo uni y. J Cell Biol. 2000;151(2):F9–F14. [4]Illanes-Ál a ez F, Má quez-Ruiz D, Má quez-Coello M, Cues a-Sancho S, Gi ón-González JA. Simila i ies and di - e ences be ween HIV and SARS-CoV-2. In J Med Sci. 2021;18(3):846. [5]Piai A, Fu Q, Sha p AK, Bighi B, B own AM, Chou JJ. NMR Model o he En i e Memb ane-In e ac ing Region o he HIV-1 Fusion P o ein and I s Pe u ba ion o Memb ane Mo phology. J Am Chem Soc. 2021;143(17):6609–15. [6]Boily M-C, Baggaley RF, Wang L, Masse B, Whi e RG, Hayes RJ, e al. He e osexual isk o HIV-1 in ec ion pe sexual ac : Sys ema ic e iew and me a-analysis o obse a ional s udies. Lance In ec Dis. 2009;9(2):118–29. [7]Baggaley RF, Boily M-C, Whi e RG, Ala y M. Risk o HIV-1 ansmission o pa en e al exposu e and blood ans usion: A sys ema ic e iew and me a-analysis. Aids. 2006;20(6):805–12. [8]Amin O, Powe s J, B icke KM, Chah oudi A. Unde s anding i al and immune in e play du ing e ical ansmission o HIV: Implica ions o cu e. F on Immunol. 2021;12:757400. [9]Chen Z, Julg B. The apeu ic accines o he ea men o HIV. T ansl Res. 2020;223:61–75. [10]Bailon L, Mo he B, Be man L, B ande C. No el app oaches owa ds a unc ional cu e o HIV/AIDS. D ugs. 2020;80(9):859–68. [11]Mo he B, Rosás-Umbe M, Coll P, Manza do C, Pue as MC, Mo ón-López S, e al. HIVcons accines and omidepsin in ea ly- ea ed HIV-1-in ec ed indi iduals: Sa e y, immuno- genici y and effec on he i al ese oi (S udy BCN02). F on immunol. 2020;11:823. [12]Webs e RG, Mon o AS, B aciale TJ, Lamb RA. Tex book o influenza. Ge many: Wiley; 2014. [13]Dadonai e B, Gilbe son B, Knigh ML, T i ko ic S, Rockman S, Laede ach A, e al. The s uc u e o he influenza A i us genome. Na Mic obiol. 2019;4(11):1781–9. [14]B anks on G, Gi e man L, Hi ji Z, Lemieux C, Ga dam M. T ansmission o influenza A in human beings. Lance In ec Dis. 2007;7(4):257–65. [15]Mon o AS, G a ens ein S, Ellio M, Colopy M, Schweinle J. Clinical signs and symp oms p edic ing influenza in ec ion. A ch In e n Med. 2000;160(21):3243–7. [16]Si anandy P, Xien FZ, Ki LW, Wei YT, En KH, Lynn LC. A e iew on cu en ends in he ea men o human in ec ion wi h H7N9-a ian influenza A. J In ec public heal h. 2019;12(2):153–8. [17]Ma y AM, Jones MK. The no el co ona i us (SARS-CoV-2)is a one heal h issue. One Heal h. 2020;9:100123. [18]Vela an TP, Meye CG. The COVID‐19 epidemic. T op Med In Heal h. 2020;25(3):278. [19]Wille M, Holmes EC. Wild bi ds as ese oi s o di e se and abundan gamma-and del aco ona i uses. FEMS Mic obiol Re . 2020;44(5):631–44. [20]Weiss C, Ca ie e M, Fusco L, Capua I, Regla-Na a JA, Pasquali M, e al. Towa d nano echnology-enabled app oaches agains he COVID-19 pandemic. ACS Nano. 2020;14(6):6383–406. [21]Tao K, Tzou PL, Nouhin J, Gup a RK, de Oli ei a T, Kosako sky Pond SL, e al. The biological and clinical significance o eme ging SARS-CoV-2 a ian s. Na Re Gene . 2021;22(12):757–73. [22]Izumi H, Nafie LA, Duko RK. Con o ma ional a iabili y co - ela ion p edic ion o ansmissibili y and neu aliza ion escape abili y o mul iple mu a ion SARS-CoV-2 s ains using SSSCP eds. ACS Omega. 2021;6(29):19323–9. [23]Zhao S, Ran J, Han L. Explo ing he in e ac ion be ween E484K and N501Y subs i u ions o SARS-CoV-2 in shaping he ansmission ad an age o COVID-19 in B azil: A Modeling S udy. Am J T op Med Hyg. 2021;105(5):1247. [24]Tegally H, Wilkinson E, Gio ane i M, I anzadeh A, Fonseca V, Giandha i J, e al. De ec ion o a SARS-CoV-2 a ian o con- ce n in Sou h A ica. Na u e. 2021;592(7854):438–43. [25]Volz E, Mish a S, Chand M, Ba e JC, Johnson R, Geidelbe g L, e al. Assessing ansmissibili y o SARS-CoV-2 lineage B. 1.1. 7 in England. Na u e. 2021;593(7858):266–9. [26]Da ies NG, Ja is CI, Edmunds WJ, Jewell NP, Diaz-O daz K, Keogh RH. Inc eased mo ali y in communi y- es ed cases o SARS-CoV-2 lineage B. 1.1. 7. Na u e. 2021;593(7858):270–4. [27]Ha WS, Mille E, And ews NJ, Waigh P, Maini PK, Funk S, e al. Gene a ion ime o he alpha and del a SARS-CoV-2 a ian s: An epidemiological analysis. Lance In ec Dis. 2022;22(5):603–10. [28]Dha MS, Ma wal R, Vs R, Ponnusamy K, Jolly B, Bhoya RC, e al. Genomic cha ac e iza ion and epidemiology o an eme ging SARS-CoV-2 a ian in Delhi, India. Science. 2021;374(6570):995–9. [29]McCallum M, Walls AC, Sp ouse KR, Bowen JE, Rosen LE, Dang HV, e al. Molecula basis o immune e asion by he Del a and Kappa SARS-CoV-2 a ian s. Science. 2021;374(6575):1621–6. [30]Fa ia NR, Mellan TA, Whi ake C, Cla o IM, Candido DD, Mish a S, e al. Genomics and epidemiology o he P. 1 SARS- CoV-2 lineage in Manaus, B azil. Science. 2021;372(6544):815–21. [31]Due R, Dima ino D, Ma ie C, Zappile P, Wang G, Ligh e J, e al. Dominance o Alpha and Io a a ian s in SARS-CoV-2 accine b eak h ough in ec ions in New Yo k Ci y. J Clin In es iga ion. 2021;131(18):1. [32]Alizon S, Haim-Boukobza S, Foulongne V, Ve du me L, T ombe -Paolan oni S, Leco che E, e al. Rapid sp ead o he SARS-CoV-2 Del a a ian in some F ench egions, June 2021. Eu osu eillance. 2021;26(28):2100573. [33]Ace edo ML, Alonso-Paloma es L, Bus aman e A, Gagge o A, Pa edes F, Co és CP, e al. In ec i i y and immune escape o he new SARS-CoV-2 a ian o in e es Lambda. MedRxi . 2021. [34]Da ies NG, Abbo S, Ba na d RC, Ja is CI, Kucha ski AJ, Munday JD, e al. Es ima ed ansmissibili y and impac o SARS-CoV-2 lineage B. 1.1. 7 in England. Science. 2021;372(6538):eabg3055. [35]Xie X, Han J-B, Ma G, Feng X-L, Li X, Zou Q-C, e al. Eme ging SARS-CoV-2 B. 1.621/Mu a ian is p ominen ly esis an o inac i a ed accine-elici ed an ibodies. Zool Res. 2021;42(6):789. [36]Ghosh N, Nandi S, Saha I. A e iew on e olu ion o eme ging SARS-CoV-2 a ian s based on spike glycop o ein. In Immunopha macol. 2022;105:108565. 18 Ma jan Mo iei e al. [37]Langone M, Pe a L, Cellama e C, Fe a is M, Guzzina i R, Ma ioli D, e al. SARS-CoV-2 in wa e se ices: P esence and impac s. En i on Pollu . 2021;268:115806. [38]Asadi S, Bou ie N, Wexle AS, Ris enpa WD. The co ona- i us pandemic and ae osols: Does COVID-19 ansmi ia expi a o y pa icles?. Ae osol Sci Technol; 2020;54(6):635–8. [39]Yépiz-Gómez MS, Ge ba CP, B igh KR. Su i al o espi a o y i uses on esh p oduce. Food En i on Vi ol. 2013;5(3):150–6. [40]McKinney KR, Gong YY, Lewis TG. En i onmen al ansmis- sion o SARS a Amoy Ga dens. J En i on Heal h. 2006;68(9):26. [41]Ami ian ES. Po en ial ecal ansmission o SARS-CoV-2: Cu en e idence and implica ions o public heal h. In J In ec Dis. 2020;95:363–70. [42]Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. E idence o gas oin es inal in ec ion o SARS-CoV-2. Gas oen e ology. 2020;158(6):1831–3.e3. [43]Du L, Yang Y, Zhang X, Li F. Recen ad ances in nano ech- nology-based COVID-19 accines and he apeu ic an ibodies. Nanoscale. 2022;14(4):1054–74. [44]Pales ino G, Ga cía-Sil a I, González-O ega O, Rosales- Mendoza S. Can nano echnology help in he figh agains COVID-19? Expe Re An i-In ec The . 2020;18(9):849–64. [45]Rai M, Bonde S, Yada A, Bhowmik A, Ra hod S, Ingle P, e al. Nano echnology as a shield agains COVID-19: Cu en ad ancemen and limi a ions. Vi uses. 2021;13(7):1224. [46]Mo iei M, Abou alebi F, Fo ouzan a M, Do miani K, Nas - Es ahani MH, Mi ahmadi-Za e SZ. Sma co-deli e y o miR- 34a and cy o oxic pep ides (LTX-315 and meli in)by chi - osan based polyelec oly e nanoca ie s o specific cance cell dea h induc ion. Ma e Sci Eng C. 2021;128:112258. [47]Tsang HF, Chan LWC, Cho WCS, Yu ACS, Yim AKY, Chan AKC, e al. An upda e on COVID-19 pandemic: The epidemiology, pa hogenesis, p e en ion and ea men s a egies. Expe Re An i-In ec The . 2021;19(7):877–88. [48]Mao L, Chen Z, Wang Y, Chen C. Design and applica ion o nanopa icles as accine adju an s agains human co ona i us in ec ion. J Ino g Biochem. 2021;219:111454. [49]Duan Y, Wang S, Zhang Q, Gao W, Zhang L. Nanopa icle app oaches agains SARS-CoV-2 in ec ion. Cu OpSolid S a e Ma e Sci. 2021;25(6):100964. [50]Pa i R, She so M, Sonawane A. Nanopa icle accines agains in ec ious diseases. F on Immunology. 2018;9:2224. [51]Zhang N, Li C, Jiang S, Du L. Recen ad ances in he de el- opmen o i us-like pa icle-based fla i i us accines. Vaccines. 2020;8(3):481. [52]Zhang N-N, Li X-F, Deng Y-Q, Zhao H, Huang Y-J, Yang G, e al. A he mos able mRNA accine agains COVID-19. Cell. 2020;182(5):1271–83.e16. [53]Laczkó D, Hogan MJ, Toulmin SA, Hicks P, Lede e K, Gaude e BT, e al. A single immuniza ion wi h nucleoside- modified mRNA accines elici s s ong cellula and humo al immune esponses agains SARS-CoV-2 in mice. Immuni y. 2020;53(4):724–32.e7. [54]Polack FP, Thomas SJ, Ki chin N, Absalon J, Gu man A, Lockha S, e al. Sa e y and efficacy o he BNT162b2 mRNA Co id-19 accine. N Engl J Med. 2020;383(27):2603–15. [55]Walsh EE, F enck J RW, Falsey AR, Ki chin N, Absalon J, Gu man A, e al. Sa e y and immunogenici y o wo RNA- based Co id-19 accine candida es. N Engl J Med. 2020;383(25):2439–50. [56]Kaise RA, Halle MC, Ap al e P, Ke schne H, Cejka D. Compa ison o BNT162b2 (Pfize –BioN ech)and mRNA-1273 (Mode na)SARS-CoV-2 mRNA accine immunogenici y in dialysis pa ien s. Kidney In . 2021;100(3):697–8. [57]Huang WC, Zhou S, He X, Chiem K, Mab ouk MT, Nissly RH, e al. SARS‐CoV‐2 RBD neu alizing an ibody induc ion is enhanced by pa icula e accina ion. Ad Ma e . 2020;32(50):2005637. [58]Peng S, Cao F, Xia Y, Gao XD, Dai L, Yan J, e al. Pa icula e alum ia picke ing emulsion o an enhanced COVID‐19 ac- cine adju an . Ad Ma e . 2020;32(40):2004210. [59]Wang N, Shang J, Jiang S, Du L. Subuni accines agains eme ging pa hogenic human co ona i uses. F on Mic obiol. 2020;11:298. [60]Kanekiyo M, Wei C-J, Yassine HM, McTamney PM, Boying on JC, Whi le JR, e al. Sel -assembling influenza nanopa icle accines elici b oadly neu alizing H1N1 an i- bodies. Na u e. 2013;499(7456):102–6. [61]Toka lian T, Read BJ, Jones CA, Kulp DW, Menis S, Chang JY, e al. Inna e immune ecogni ion o glycans a ge s HIV nanopa icle immunogens o ge minal cen e s. Science. 2019;363(6427):649–54. [62]Tan TK, Rijal P, Rahikainen R, Keeble AH, Schimanski L, Hussain S, e al. A COVID-19 accine candida e using SpyCa che mul ime iza ion o he SARS-CoV-2 spike p o ein ecep o -binding domain induces po en neu alising an i- body esponses. Na Commun. 2021;12(1):1–16. [63]Walls AC, Fiala B, Schä e A, W enn S, Pham MN, Mu phy M, e al. Elici a ion o po en neu alizing an ibody esponses by designed p o ein nanopa icle accines o SARS-CoV-2. Cell. 2020;183(5):1367–82.e17. [64]Powell AE, Zhang K, Sanyal M, Tang S, Weidenbache PA, Li S, e al. A single immuniza ion wi h spike- unc ionalized e i in accines elici s neu alizing an ibody esponses agains SARS-CoV-2 in mice. ACS Cen Sci. 2021;7(1):183–99. [65]Wang W, Huang B, Zhu Y, Tan W, Zhu M. Fe i in nanopa icle- based SARS-CoV-2 RBD accine induces a pe sis en an i- body esponse and long- e m memo y in mice. Cell Mol Immunol. 2021;18(3):749–51. [66]Saunde s KO, Lee E, Pa ks R, Ma inez DR, Li D, Chen H, e al. Neu alizing an ibody accine o pandemic and p e-eme - gen co ona i uses. Na u e. 2021;594(7864):553–9. [67]Ma X, Zou F, Yu F, Li R, Yuan Y, Zhang Y, e al. Nanopa icle accines based on he ecep o binding domain (RBD)and hep ad epea (HR)o SARS-CoV-2 elici obus p o ec i e immune esponses. Immuni y. 2020;53(6):1315–30.e9. [68]Huang X, Kon E, Han X, Zhang X, Kong N, Mi chell MJ, e al. Nano echnology-based s a egies agains SARS-CoV-2 a - ian s. Na Nano echnol. 2022;17(10):1027–37. [69]Kuma N, Admane N, Kuma i A, Sood D, G o e S, P ajapa i VK, e al. Cy o oxic T-lymphocy e elici ed accine agains SARS-CoV-2 employing immunoin o ma ics ame- wo k. Sci Rep. 2021;11(1):1–14. [70]Sahoo B, Kan K, Rai NK, Chaudha y DK. Iden ifica ion o T-cell epi opes in p o eins o no el human co ona i us, SARS-Co -2 o accine de elopmen . In J Appl Biol Pha m Technol. 2020;11(2):37–45. SARS-COV-2 and nano echnology 19 [71]Chan Y, Ng SW, Singh SK, Gula i M, Gup a G, Chaudha y SK, e al. Re olu ionizing polyme -based nanopa icle-linked accines o a ge ing espi a o y i uses: A pe spec i e. Li e Sci. 2021;280:119744. [72]Mohamed SH, A a a AS, Mady WH, Fahmy HA, Ome LM, Mo si RE. P epa a ion and immunological e alua ion o inac i a ed a ian influenza i us accine encapsula ed in chi osan nanopa icles. Biologicals. 2018;51:46–53. [73]Huang T, Song X, Jing J, Zhao K, Shen Y, Zhang X, e al. Chi osan-DNA nanopa icles enhanced he immunogenici y o mul i alen DNA accina ion on mice agains T uepe ella pyogenes in ec ion. J Nanobio echnol. 2018;16(1):1–15. [74]Ve heul RJ, Slü e B, Bal SM, Bouws a JA, Jiskoo W, Hennink WE. Co alen ly s abilized ime hyl chi osan-hya- lu onic acid nanopa icles o nasal and in ade mal acci- na ion. J Con olled Release. 2011;156(1):46–52. [75]Yu H, Lin H, Xie Y, Qu M, Jiang M, Shi J, e al. MUC1 accines using β-cyclodex in g a ed chi osan (CS–g–CD)as ca ie ia hos -gues in e ac ion elici obus immune esponses. Chin Chem Le . 2022;33(11):4882–5. [76]Rocha CE, Sil a MF, Guedes AC, Ca alho TP, Ecks ein C, Ribei o NQ, e al. Algina e-chi osan mic ocapsules imp o e accine po en ial o gamma-i adia ed Lis e ia monocy o- genes agains lis e iosis in mu ine model. In J Biol Mac omolecules. 2021;176:567–77. [77]S iepel RT, Ba y CJ, MacRaild CA, No on RS, Bachelde E, Ainslie KM. Me ozoi e su ace p o ein 2 adso bed on o ace ala ed dex an mic opa icles o mala ia accina ion. In J Pha maceu ics. 2021;593:120168. [78]Nakahashi-Ouchida R, Yuki Y, Kiyono H. Ca ionic pullulan nanogel as a sa e and effec i e nasal accine deli e y sys em o espi a o y in ec ious diseases. Hum Vaccines Immuno he . 2018;14(9):2189–93. [79]Fe ell KC, S ewa EL, Counoupas C, Ashhu s TM, B i on WJ, Pe o sky N, e al. In apulmona y accina ion wi h del a- inulin adju an s imula es non-pola ised chemo ac ic sig- nalling and di e se cellula in e ac ion. Mucosal Immunol. 2021;14(3):762–73. [80]Bandei a AC, de Oli ei a Ma os A, E angelis a BS, da Sil a SM, Nagib PRA, de Mo aes C espo A, e al. Is i possible o ack in acellula chi osan nanopa icles using magne ic nanopa icles as con as agen ? Bioo g Med Chem. 2019;27(12):2637–43. [81]Hi ema h J, Kang K-I, Xia M, Elaish M, Binjawadagi B, Ouyang K, e al. En apmen o H1N1 influenza i us de i ed conse ed pep ides in PLGA nanopa icles enhances T cell esponse and accine efficacy in pigs. PLoS One. 2016;11(4):e0151922. [82]Singh J, Pandi S, B amwell VW, Alpa HO. Diph he ia oxoid loaded poly-(ε-cap olac one)nanopa icles as mucosal ac- cine deli e y sys ems. Me hods. 2006;38(2):96–105. [83]Zhang D, A ochina-Vasse man EN, Mau ya DS, Liu M, Xiao Q, Lu J, e al. Ta ge ed deli e y o mRNA wi h one-componen ionizable amphiphilic janus dend ime s. J Am Chem Soc. 2021;143(43):17975–82. [84]Ren S, Guo L, Wang C, Ru J, Yang Y, Wang Y, e al. Cons uc ion o an effec i e deli e y sys em o DNA accines using biodeg adable polylac ic acid based mic osphe es. J Biomed Nano echnol. 2021;17(5):971–80. [85]S ephens LM, Ross KA, Walds ein KA, Legge KL, McLellan JS, Na asimhan B, e al. P e usion F–based polyanhyd ide nano accine induces bo h humo al and cell-media ed immuni y esul ing in long-las ing p o ec ion agains espi a o y syncy ial i us. J Immunol. 2021;206(9):2122–34. [86]Klimek L, No ak N, Cabanillas B, Ju el M, Bousque J, Akdis CA. Alle genic componen s o he mRNA‐1273 accine o COVID‐19: Possible in ol emen o polye hylene glycol and IgG‐media ed complemen ac i a ion. Alle gy. 2021;76(11):3307–13. [87]Guo S, Fu D, U upo a A, Sun D, Zhou M, Jin Z, e al. Applica ions o polyme -based nanopa icles in accine field. Nano echnol Re . 2019;8(1):143–55. [88]Hess KL, Medin z IL, Jewell CM. Designing ino ganic nano- ma e ials o accines and immuno he apies. Nano Today. 2019;27:73–98. [89]Zhou Q, Zhang Y, Du J, Li Y, Zhou Y, Fu Q, e al. Diffe en -sized gold nanopa icle ac i a o /an igen inc eases dend i ic cells accumula ion in li e -d aining lymph nodes and CD8 +T cell esponses. ACS Nano. 2016;10(2):2678–92. [90]Hu Z, Song B, Xu L, Zhong Y, Peng F, Ji X, e al. Aqueous syn hesized quan um do s in e e e wi h he NF-κB pa hway and con e an i- umo , an i- i al and an i-inflamma o y effec s. Bioma e ials. 2016;108:187–96. [91]Ve siani AF, As iga aga RG, Rocha ES, Ba boza APM, K oon EG, Rachid MA, e al. Mul i-walled ca bon nano ubes unc ionalized wi h ecombinan Dengue i us 3 en elope p o eins induce significan and specific immune esponses in mice. J Nanobio echnol. 2017;15(1):1–13. [92]Pesca o i M, Bedogne i D, Ven u elli E, Ména d-Moyon C, Be na dini C, Mu esu E, e al. Func ionalized ca bon nano- ubes as immunomodula o sys ems. Bioma e ials. 2013;34(18):4395–403. [93]Qiao L, Chen M, Li S, Hu J, Gong C, Zhang Z, e al. A pep ide- based subuni candida e accine agains SARS-CoV-2 deli - e ed by biodeg adable mesopo ous silica nanopa icles induced high humo al and cellula immuni y in mice. Bioma e Sci. 2021;9(21):7287–96. [94]Mo amedi‐sedeh F, Saboo izadeh A, Khalili I, Sha ba da an M, Wijewa dana V, A babi A. Ca boxyme hyl chi osan bounded i on oxide nanopa icles and gamma‐ i adia ed a ian influenza sub ype H9N2 accine o de el- opmen o immuni y on mouse and chicken. Ve Med Sci. 2021;8(2):626–34. [95]O ecchioni M, Bedogne i D, Newman L, Fuoco C, Spada F, Hend ickx W, e al. Single-cell mass cy ome y and an- sc ip ome p ofiling e eal he impac o g aphene on human immune cells. Na Commun. 2017;8(1):1–14. [96]Xu L, Xiang J, Liu Y, Xu J, Luo Y, Feng L, e al. Func ionalized g aphene oxide se es as a no el accine nano-adju an o obus s imula ion o cellula immuni y. Nanoscale. 2016;8(6):3785–95. [97]Bilyy R, Pagneux Q, F ançois N, Bila G, G y sko R, Lebedin Y, e al. Rapid gene a ion o co ona i al immuni y using ecombinan pep ide modified nanodiamonds. Pa hogens. 2021;10(7):861. [98]Cao W, He L, Cao W, Huang X, Jia K, Dai J. Recen p og ess o g aphene oxide as a po en ial accine ca ie and adju an . Ac a bioma e ialia. 2020;112:14–28. 20 Ma jan Mo iei e al. [99]Bakka MR, Fa aag AHI, Soliman ER, Fouda MS, Sa guos AMM, McLean GR, e al. Rhamnolipids nano- micelles as a po en ial hand sani ize . An ibio ics. 2021;10(7):751. [100]Monge FA, Jagadesan P, Bondu V, Donabedian PL, Is a L, Chi EY, e al. Highly effec i e inac i a ion o SARS-CoV-2by conjuga ed polyme s and oligome s. ACS Appl Ma e In e aces. 2020;12(50):55688–95. [101]Chowdhu y MA, Shu ho MBA, Shahid MA, Haque AM, Kashem MA, Lam SS, e al. P ospec o biobased an i i al ace mask o limi he co ona i us ou b eak. En i on Res. 2021;192:110294. [102]Zhong H, Zhu Z, Lin J, Cheung CF, Lu VL, Yan F, e al. Reusable and ecyclable g aphene masks wi h ou s anding supe hy- d ophobic and pho o he mal pe o mances. ACS nano. 2020;14(5):6213–21. [103]Kasbe PS, Gade H, Liu S, Chase GG, Xu W. Ul a hin polydo- pamine-g aphene oxide hyb id coa ings on polyme fil e s wi h imp o ed fil a ion pe o mance and unc ionali ies. ACS Appl Bio Ma e . 2021;4(6):5180–8. [104]Gopal V, Nilsson-Payan BE, F ench H, Siege s JY, Yung W-S, Ha dwick M, e al. Zinc-embedded polyamide ab ics inac i- a e SARS-CoV-2 and influenza a i us. ACS Appl Ma e In e aces. 2021;13(26):30317–25. [105]Jung S, Yang J-Y, Byeon E-Y, Kim D-G, Lee D-G, Ryoo S, e al. Coppe -coa ed polyp opylene fil e ace mask wi h SARS- COV-2 an i i al abili y. Polyme s. 2021;13(9):1367. [106]Joe YH, Pa k DH, Hwang J. E alua ion o Ag nanopa icle coa ed ai fil e agains ae osolized i us: An i- i al efficiency wi h dus loading. J Haza d Ma e . 2016;301:547–53. [107]Kuma A, Sha ma A, Chen Y, Jones MM, Vanyo ST, Li C, e al. Coppe @ ZIF‐8 co e‐shell nanowi es o eusable an imic o- bial ace masks. Ad Func Ma e . 2021;31(10):2008054. [108]Balagna C, Pe e o S, Pe ci alle E, Nepi a EV, Fe a is M. Vi ucidal effec agains co ona i us SARS-CoV-2 o a sil e nanoclus e /silica composi e spu e ed coa ing. Open Ce am. 2020;1:100006. [109]Abbas WA, Shaheen BS, Ghanem LG, Badawy IM, Abodouh MM, Abdou SM, e al. Cos -effec i e ace mask fil e based on hyb id composi e nanofib ous laye s wi h high fil- a ion efficiency. Langmui . 2021;37(24):7492–502. [110]Kuma S, Ka macha ya M, Joshi SR, Gulenko O, Pa k J, Kim G- H, e al. Pho oac i e an i i al ace mask wi h sel -s e iliza ion and eusabili y. Nano Le . 2020;21(1):337–43. [111]He R, Li J, Chen M, Zhang S, Cheng Y, Ning X, e al. Tailo ing mois u e elec oac i e Ag/Zn@ co on coupled wi h elec o- spun PVDF/PS nanofibe s o an imic obial ace masks. J Haza d Ma e . 2022;428:128239. [112]Ciejka J, Wolski K, Nowakowska M, Py c K, Szczubiałka K. Biopolyme ic nano/mic osphe es o selec i e and e e sible adso p ion o co ona i uses. Ma e Sci Eng C. 2017;76:735–42. [113]Gup a I, Chak abo y J, Roy S, Fa inas ET, Mi a S. Nanoca bon immobilized memb anes o gene a ing bac e ia and endo oxin ee wa e ia memb ane dis illa ion. Sep Pu i Technol. 2021;259:118133. [114]Zheng X, Shen Z-P, Cheng C, Shi L, Cheng R, Yuan D-H. Pho oca aly ic disin ec ion pe o mance in i us and i us/ bac e ia sys em by Cu-TiO 2 nanofibe s unde isible ligh . En i on Pollu . 2018;237:452–9. [115]Kusiak-Nejman E, Mo awski AW. TiO 2 /g aphene-based nanocomposi es o wa e ea men : A b ie o e iew o cha ge ca ie ans e , an imic obial and pho oca aly ic pe o mance. Appl Ca al B En i on. 2019;253:179–86. [116]Liu H, Huang J, Mao J, Chen Z, Chen G, Lai Y. T anspa en an ibac e ial nanofibe ai fil e s wi h highly efficien mois u e esis ance o sus ainable pa icula e ma e cap- u e. Iscience. 2019;19:214–23. [117]S an o d MG, Li JT, Chen Y, McHugh EA, Liopo A, Xiao H, e al. Sel -s e ilizing lase -induced g aphene bac e ial ai fil e . ACS nano. 2019;13(10):11912–20. [118]Sun W-H, Hui L-F, Yang Q, Zhao G-D. Nanofil a ion fil e pape based on mul i-walled ca bon nano ubes and cellulose fil e pape s. RSC Ad . 2021;11(2):1194–9. [119]Deshmukh SP, Pa il S, Mullani S, Deleka S. Sil e nanopa - icles as an effec i e disin ec an : A e iew. Ma e Sci Eng C. 2019;97:954–65. [120]Ko Y-S, Joe YH, Seo M, Lim K, Hwang J, Woo K. P omp and syne gis ic an ibac e ial ac i i y o sil e nanopa icle-deco- a ed silica hyb id pa icles on ai fil a ion. J Ma e Chem B. 2014;2(39):6714–22. [121]Han J, Chen L, Duan S-M, Yang Q-X, Yang M, Gao C, e al. Efficien and quick inac i a ion o SARS co ona i us and o he mic obes exposed o he su aces o some me al ca - alys s. Biomed En i on Sci BES. 2005;18(3):176–80. [122]Wang I-J, Chen Y-C, Su C, Tsai M-H, Shen W-T, Bai C-H, e al. Effec i eness o he Nanosil e /TiO 2 -chi osan an i i al fil e on he emo al o i al ae osols. J Ae osol Med Pulm D ug Deli e y. 2021;34(5):293–302. [123]Heo KJ, Jeong SB, Shin J, Hwang GB, Ko HS, Kim Y, e al. Wa e - epellen TiO 2 -o ganic dye-based ai fil e s o effi- cien isible-ligh -ac i a ed pho ochemical inac i a ion agains bioae osols. Nano Le . 2020;21(4):1576–83. [124]L D, Wang R, Tang G, Mou Z, Lei J, Han J, e al. Eco iendly elec ospun memb anes loaded wi h isible-ligh - esponding nanopa icles o mul i unc ional usages: Highly efficien ai fil a ion, dye sca enging, and bac e icidal ac i i y. ACS Appl Ma e In e aces. 2019;11(13):12880–9. [125]Milewska A, Chi Y, Szczepanski A, Ba e o-Du an E, Liu K, Liu D, e al. HTCC as a highly effec i e polyme ic inhibi o o SARS-CoV-2 and MERS-CoV. BioRxi . 2020. [126]Khaiboullina S, Uppal T, Dhaba de N, Sub amanian VR, Ve ma SC. Inac i a ion o human co ona i us by i ania nanopa icle coa ings and UVC adia ion: Th owing ligh on SARS-CoV-2. Vi uses. 2020;13(1):19. [127]Je emiah SS, Miyakawa K, Mo i a T, Yamaoka Y, Ryo A. Po en an i i al effec o sil e nanopa icles on SARS-CoV-2. Biochemical biophysical Res Commun. 2020;533(1):195–200. [128]Zhu P, Wang Y, Chu H, Wang L. Supe hyd ophobici y p e- en ing su ace con amina ion as a no el s a egy agains COVID-19. J Colloid In e ace Sci. 2021;600:613–9. [129]Hamouda T, Ib ahim HM, Ka a y H, Mashaly H, Mohamed NH, Aly NM. P epa a ion o cellulose-based wipes ea ed wi h an imic obial and an i i al sil e nanopa icles as no el effec i e high-pe o mance co ona i us figh e . In J Biol mac omolecules. 2021;181:990–1002. [130]Behzadinasab S, Chin A, Hosseini M, Poon L, Ducke WA. A su ace coa ing ha apidly inac i a es SARS-CoV-2. ACS Appl Ma e In e aces. 2020;12(31):34723–7. SARS-COV-2 and nano echnology 21 [131]Asadi S, Bou ie N, Wexle AS, Ris enpa WD. The co ona- i us pandemic and ae osols: Does COVID-19 ansmi ia expi a o y pa icles?. Ae osol Sci Technol; 2020;54(6):635–8. [132]Mallakpou S, Azadi E, Hussain CM. Fab ica ion o ai fil e s wi h ad anced fil a ion pe o mance o emo al o i al ae osols and con ol he sp ead o COVID-19. Ad Colloid In e ace Sci. 2022;303:102653. [133]Algho aibi I, Aloma i S. Diffe en me hods o nanofibe design and ab ica ion. Handbook o Nanofibe s; 2018. p. 1–46. [134]Bha acha jee S, Joshi R, Yasi M, Adhika i A, Chugh ai AA, Heslop D, e al. G aphene-and Nanopa icle-Embedded An imic obial and Biocompa ible Co on/Silk Fab ics o P o ec i e Clo hing. ACS Appl Bio Ma e . 2021;4(8):6175–85. [135]Jeong SB, Lee DU, Lee BJ, Heo KJ, Kim DW, Hwang GB, e al. Pho obiocidal- iboelec ic nanolaye coa ing o pho osensi- ize /silica–alumina o eusable and isible-ligh -d i en an i- bac e ial/an i i al ai fil e s. Chem Eng J. 2022;440:135830. [136]Bo kow G, Zhou SS, Page T, Gabbay J. A no el an i-influenza coppe oxide con aining espi a o y ace mask. PLoS One. 2010;5(6):e11295. [137]Ka agoz S, Ki emi le NB, Sa p G, Pekdemi S, Salem S, Goksu AG, e al. An ibac e ial, an i i al, and sel -cleaning ma s wi h sensing capabili ies based on elec ospun nano- fibe s deco a ed wi h ZnO nano ods and Ag nanopa icles o p o ec i e clo hing applica ions. ACS Appl Ma e In e aces. 2021;13(4):5678–90. [138]Lee B-Y, Behle K, Ku oglu ME, Wynosky-DolfiMA, Res RF, Gogo si Y. Ti anium dioxide-coa ed nanofibe s o ad anced fil e s. J Nanopa Res. 2010;12(7):2511–9. [139]Ramaiah GB, Tegegne A, Melese B. De elopmen s in nano- ma e ials and analysing i s ole in figh ing COVID-19. Ma e Today P oc. 2021;47:4357–63. [140]Phuna ZX, Panda BP, Hawala Shi asheka egowda NK, Madha an P. Nanop o ec ion om SARS-COV-2: Would nano echnology help in Pe sonal P o ec ion Equipmen (PPE) o con ol he ansmission o COVID-19? In J En i on Heal h Res. 2022;1–30. [141]Fib iana F, Amalia AV, Mun amah S, Ul a L, A yan i S. An imic obial ac i i ies o g een syn hesized sil e nano- pa icles om Ma chan ia sp. ex ac : Tes ing an alcohol- ee hand sani ize p oduc o mula. J mic obiol Bio echnol Food Sci. 2020;9(6):1034–8. [142]Malabadi RB, Kolka KP, Me i NT, Chalanna a RK. Role o plan based hand sani ize s du ing he ecen ou b eak o co ona i us (SARS-CoV-2)disease (Co id-19). Significances Bioeng Biosci. 2021;5(1):458–68. [143]T an HN, Le GT, Nguyen DT, Juang R-S, Rinklebe J, Bha naga A, e al. SARS-CoV-2 co ona i us in wa e and was ewa e : A c i ical e iew abou p esence and conce n. En i on Res. 2021;193:110265. [144]Romano-Be and S, Glele LA, G andbas ien B, Lepelle ie D. P e en ing SARS-CoV-2 ansmission in ehabili a ion pools and he apeu ic wa e en i onmen s. J Hosp In ec . 2020;105(4):625–7. [145]Rimoldi SG, S e ani F, Gigan iello A, Polesello S, Comanda o e F, Mile o D, e al. P esence and in ec i i y o SARS-CoV-2 i us in was ewa e s and i e s. Sci To al En i on. 2020;744:140911. [146]Nasi AM, Adam MR, Kamal SNEAM, Jaa a J, O hman MHD, Ismail AF, e al. A e iew o he po en ial o con en ional and ad anced memb ane echnology in he emo al o pa hogens om was ewa e . Sep Pu i Technol. 2022;286:120454. [147]Ha dika M, Ikne LA, Felix V, P esson LK, Rabe AB, Hickenbo om KL, e al. Memb ane dis illa ion p o ides a dual ba ie o co ona i us and bac e iophage emo al. En i on Sci Technol Le . 2021;8(8):713–8. [148]N hunya LN, Gu ie ez L, Khumalo N, De ese S, Mamba BB, Ve lie de AR, e al. Supe hyd ophobic PVDF nanofib e mem- b anes coa ed wi h an o ganic ouling esis an hyd ophilic ac i e laye o di ec -con ac memb ane dis illa ion. Colloids Su A. 2019;575:363–72. [149]Bi yuko J, Boyds on JA, Dunning RA, Yeage JJ, Wood S, Fe is A, e al. SARS-CoV-2 is apidly inac i a ed a high empe a u e. En i on Chem Le . 2021;19(2):1773–7. [150]Soni V, Khosla A, Singh P, Nguyen V-H, Van Le Q, Sel asembian R, e al. Cu en pe spec i e in me al oxide based pho oca alys s o i us disin ec ion: A e iew. J En i on Manag. 2022;308:114617. [151]Liu L, Meng G, Chen H, Wang C, Xue Y. Pho oca aly ic disin- ec ion o diffe en ai bo ne mic oo ganisms by TiO 2 /MXene fille : Inac i a ion efficiency, ene gy consump ion and sel - epai phenomenon. J En i on Chem Eng. 2022;10:107641. [152]Nasi AM, Awang N, Hubadillah SK, Jaa a J, O hman MHD, Salleh WNW, e al. A e iew on he po en ial o pho oca alysis in comba ing SARS-CoV-2 in was ewa e . J Wa e P ocess Eng. 2021;42:102111. [153]Moo KJ, Valle DC, Li C, Kim J-H. Imp o ing he isible ligh pho oac i i y o suppo ed ulle ene pho oca alys s h ough he use o [C70] ulle ene. En i on Sci Technol. 2015;49(10):6190–7. [154]Bane jee I, Douaisi MP, Mondal D, Kane RS. Ligh -ac i a ed nano ube–po phy in conjuga es as effec i e an i i al agen s. Nano echnology. 2012;23(10):105101. [155]Łoczechin A, Sé on K, Ba as A, Gio anelli E, Belouza d S, Chen Y-T, e al. Func ional ca bon quan um do s as medical coun e measu es o human co ona i us. ACS Appl Ma e In e aces. 2019;11(46):42964–74. [156]Zhang C, Li Y, Wang C, Zheng X. Diffe en inac i a ion beha- io s and mechanisms o ep esen a i e pa hogens (Esche ichia coli bac e ia, human adeno i uses and Bacillus sub ilis spo es)in g-C3N4-based me al- ee isible-ligh - enabled pho oca aly ic disin ec ion. Sci To al En i on. 2021;755:142588. [157]Shi Y, Huang J, Zeng G, Cheng W, Hu J. Pho oca aly ic mem- b ane in wa e pu ifica ion: Is i s epping close o be d i en by isible ligh ? J Memb Sci. 2019;584:364–92. [158]Do emalen NV, Bushmake T, Mo is DH, Holb ook MG, Gamble A, Williamson BN, e al. Ae osol and su ace s abili y o SARS-CoV-2 as compa ed wi h SARS-CoV-1. N Engl J Med. 2020;382(16):1564–7. [159]Vaze N, Py gio akis G, McDe i J, Mena L, Melo A, Bedugnis A, e al. Inac i a ion o common hospi al acqui ed pa hogens on su aces and in ai u ilizing enginee ed wa e nanos uc u es (EWNS)based nano-sani ize s. Nanomedicine Nano echnol Biol Med. 2019;18:234–42. [160]E e h M, Fine J, S ama a os F, Ma hew B, Hess D, Simpse E. Heal hca e-associa ed in ec ion impac wi h bioae osol 22 Ma jan Mo iei e al. ea men and COVID-19 mi iga ion measu es. J Hosp In ec . 2021;116:69–77. [161]Blocken B, an D uenen T, Ricci A, Kang L, an HooffT, Qin P, e al. Ven ila ion and ai cleaning o limi ae osol pa icle concen a ions in a gym du ing he COVID-19 pandemic. Build En i on. 2021;193:107659. [162]Yoon K-Y, Byeon JH, Pa k J-H, Ji JH, Bae GN, Hwang J. An imic obial cha ac e is ics o sil e ae osol nanopa icles agains Bacillus sub ilis bioae osols. En i on Eng Sci. 2008;25(2):289–94. [163]Fan X, Rong L, Kong L, Li Y, Huang J, Cao Y, e al. Tug-o -wa - inspi ed bio-based ai fil e s wi h ad anced fil a ion pe - o mance. ACS Appl Ma e In e aces. 2021;13(7):8736–44. [164]Pa ial S, Kuma A, Raizada P, Van Le Q, Sel asembian R, Singh P, e al. Po en ial o G aphene based pho oca alys o an i i al ac i i y wi h emphasis on COVID-19: A e iew. J En i on Chem Eng. 2022;10:107527. [165]Lim ME, Lee Y-L, Zhang Y, Chu JJH. Pho odynamic inac i a ion o i uses using upcon e sion nanopa icles. Bioma e ials. 2012;33(6):1912–20. [166]Kaise J-P, Zuin S, Wick P. Is nano echnology e olu ionizing he pain and lacque indus y? A c i ical opinion. Sci To al En i on. 2013;442:282–9. [167]Kuma R, Nayak M, Sahoo GC, Pandey K, Sa ka MC, Ansa i Y, e al. I on oxide nanopa icles based an i i al ac i i y o H1N1 influenza A i us. J In ec Chemo he . 2019;25(5):325–9. [168]Lin N, Ve ma D, Saini N, A bi R, Muni M, Jo ic M, e al. An i i al nanopa icles o sani izing su aces: A oadmap o sel -s e ilizing agains COVID-19. Nano Today. 2021;40:101267. [169]Wiehe A, O’B ien JM, Senge MO. T ends and a ge s in an i- i al pho o he apy. Pho ochem Pho obiol Sci. 2019;18(11):2565–612. [170]Ting D, Dong N, Fang L, Lu J, Bi J, Xiao S, e al. Mul isi e inhibi o s o en e ic co ona i us: An i i al ca ionic ca bon do s based on cu cumin. ACS Appl Nano Ma e . 2018;1(10):5451–9. [171]Milewska A, Kaminski K, Ciejka J, Kosowicz K, Zeglen S, Woja ski J, e al. HTCC: B oad ange inhibi o o co ona i us en y. PLoS One. 2016;11(6):e0156552. [172]Smi h RJ, Moule MG, Sule P, Smi h T, Ci illo JD, G unlan JC. Polyelec oly e mul ilaye nanocoa ing d ama ically educes bac e ial adhesion o polyes e ab ic. ACS Bioma e Sci Eng. 2017;3(8):1845–52. [173]Ven u a BD, Cennamo M, Minopoli A, Campanile R, Censi SB, Te acciano D, e al. Colo ime ic es o as de ec ion o SARS-CoV-2 in nasal and h oa swabs. ACS Sens. 2020;5(10):3043–8. [174]Hassanzadeh P. Nano he anos ics agains COVID-19: F om mul i alen o immune- a ge ed ma e ials. J. Con olled Release. 2020;328:112–26. [175]Huang C, Wen T, Shi F-J, Zeng X-Y, Jiao Y-J. Rapid de ec ion o IgM an ibodies agains he SARS-CoV-2 i us ia colloidal gold nanopa icle-based la e al-flow assay. ACS Omega. 2020;5(21):12550–6. [176]Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, e al. De elopmen and clinical applica ion o a apid IgM‐IgG combined an ibody es o SARS‐CoV‐2 in ec ion diagnosis. J Med Vi ol. 2020;92(9):1518–24. [177]Bake AN, Richa ds S-J, Guy CS, Congdon TR, Hasan M, Zwe sloo AJ, e al. The SARS-COV-2 spike p o ein binds sialic acids and enables apid de ec ion in a la e al flow poin o ca e diagnos ic de ice. ACS Cen Sci. 2020;6(11):2046–52. [178]Moi a P, Ala ee M, Dighe K, F ieman MB, Pan D. Selec i e naked-eye de ec ion o SARS-CoV-2 media ed by N gene a ge ed an isense oligonucleo ide capped plasmonic nano- pa icles. ACS nano. 2020;14(6):7617–27. [179]Liu H, Dai E, Xiao R, Zhou Z, Zhang M, Bai Z, e al. De elopmen o a SERS-based la e al flow immunoassay o apid and ul a-sensi i e de ec ion o an i-SARS-CoV-2 IgM/ IgG in clinical samples. Sens Ac ua o s B. 2021;329:129196. [180]Chen Z, Zhang Z, Zhai X, Li Y, Lin L, Zhao H, e al. Rapid and sensi i e de ec ion o an i-SARS-CoV-2 IgG, using lan ha- nide-doped nanopa icles-based la e al flow immunoassay. Anal Chem. 2020;92(10):7226–31. [181]Wang Z, Zheng Z, Hu H, Zhou Q, Liu W, Li X, e al. A poin -o - ca e selenium nanopa icle-based es o he combined de ec ion o an i-SARS-CoV-2 IgM and IgG in human se um and blood. Lab-on-a-Chip. 2020;20(22):4255–61. [182]Wang D, He S, Wang X, Yan Y, Liu J, Wu S, e al. Rapid la e al flow immunoassay o he fluo escence de ec ion o SARS- CoV-2 RNA. Na Biomed Eng. 2020;4(12):1150–8. [183]Seo G, Lee G, Kim MJ, Baek S-H, Choi M, Ku KB, e al. Rapid de ec ion o COVID-19 causa i e i us (SARS-CoV-2)in human nasopha yngeal swab specimens using field-effec ansis o -based biosenso . ACS nano. 2020;14(4):5135–42. [184]Kho is IM, Ganganboina AB, Suzuki T, Pa k EY. Sel - assembled ch omogen-loaded polyme ic cocoon o espi a o y i us de ec ion. Nanoscale. 2021;13(1):388–96. [185]Yüce M, Filiz ekin E, Özkaya KG. COVID-19 diagnosis—A e iew o cu en me hods. Biosens Bioelec on. 2021;172:112752. [186]Kyle S. Affime p o eins: The anos ics o he u u e? T ends Biochem Sci. 2018;43(4):230–2. [187]Singh R, Hong S, Jang J. Label- ee de ec ion o influenza i uses using a educed g aphene oxide-based elec oche- mical immunosenso in eg a ed wi h a mic ofluidic pla o m. Sci Rep. 2017;7(1):1–11. [188]Qoma a WF, P imanissa DN, Amalia SH, Pu wadi FV, Zakiyah N. Effec i eness o emdesi i , lopina i / i ona i , and a ipi a i o COVID-19 ea men : A sys ema ic e iew. In J Gen Med. 2021;14:8557. [189]Fab a MJ, Falcó I, Randazzo W, Sánchez G, López-Rubio A. An i i al and an ioxidan p ope ies o ac i e algina e edible films con aining phenolic ex ac s. Food Hyd ocoll. 2018;81:96–103. [190]So ia-Ma inez L, Baue S, Giesle M, Schelhaas S, Ma e lik J, Janus K, e al. P ophylac ic an i i al ac i i y o sul a ed gly- comime ic oligome s and polyme s. J Am Chem Soc. 2020;142(11):5252–65. [191]Gün he SC, Maie JD, Ve e J, Pod alnyy N, Khanzhin N, Henne T, e al. An i i al po en ial o 3′-sialyllac ose-and 6′- sialyllac ose-conjuga ed dend i ic polyme s agains human and a ian influenza i uses. Sci Rep. 2020;10(1):1–9. [192]Donskyi IS, Nie C, Ludwig K, T impe J, Ahmed R, Quaas E, e al. G aphene shee s wi h defined dual unc ionali ies o he s ong SARS‐CoV‐2 in e ac ions. Small. 2021;17(11):2007091. SARS-COV-2 and nano echnology 23 [193]Ramos-So iano J, Reina JJ, Illescas BM, De La C uz N, Rod iguez-Pe ez L, Lasala F, e al. Syn hesis o highly effi- cien mul i alen disaccha ide/[60] ulle ene nanoballs o eme gen i uses. J Am Chem Soc. 2019;141(38):15403–12. [194]Tong T, Hu H, Zhou J, Deng S, Zhang X, Tang W, e al. Glycy hizic‐acid‐based ca bon do s wi h high an i i al ac i i y by mul isi e inhibi ion mechanisms. Small. 2020;16(13):1906206. [195]Kim H-E, Lee H-J, Kim MS, Kim T, Lee H, Kim H-H, e al. Diffe en ial mic obicidal effec s o bime allic i on–coppe nanopa icles on Esche ichia coli and MS2 Coliphage. En i on Sci Technol. 2019;53(5):2679–87. [196]Kim J, Mukhe jee A, Nelson D, Jozic A, Sahay G. Rapid gen- e a ion o ci cula ing and mucosal decoy ACE2 using mRNA nano he apeu ics o he po en ial ea men o SARS-CoV-2. BioRxi . 2020. [197]Wang C, Wang S, Chen Y, Zhao J, Han S, Zhao G, e al. Memb ane nanopa icles de i ed om ACE2- ich cells block SARS-CoV-2 in ec ion. ACS nano. 2021;15(4):6340–51. [198]Su na B, Kam an MZ, Shah AS, Dha S. Clinically app o ed an i i al d ug in an o ally adminis able nanopa icle o COVID-19. ACS Pha macol T ansl Sci. 2020;3(6):1371–80. [199]Zhang Q, Honko A, Zhou J, Gong H, Downs SN, Vasquez JH, e al. Cellula nanosponges inhibi SARS-CoV-2 in ec i i y. Nano Le . 2020;20(7):5570–4. [200]Mo ad R, Akba i M, Rezaee P, Koochaki A, Maaza M, Jamshidi Z. Fi s p inciple simula ion o coa ed hyd oxy- chlo oquine on Ag, Au and P nanopa icles. Sci Rep. 2021;11(1):1–9. [201]Neu u h M, Wang X, Tolba E, Liebe wi h I, Wang S, Sch öde HC, e al. The ino ganic polyme , polyphospha e, blocks binding o SARS-CoV-2 spike p o ein o ACE2 ecep o a physiological concen a ions. Biochem Pha macol. 2020;182:114215. [202]Ma ínez-Abad A, Ocio M, Laga ón J, Sánchez G. E alua ion o sil e -in used polylac ide films o inac i a ion o Salmonella and eline calici i us in i o and on esh-cu ege ables. In J Food Mic obiol. 2013;162(1):89–94. [203]Hu R, Li S, Kong F, Hou R, Guan X, Guo F. Inhibi ion effec o sil e nanopa icles on he pes simplex i us 2. Gene Mol Res. 2014;13(3):7022–8. [204]Pa k HH, Pa k S, Ko G, Woo K. Magne ic hyb id colloids deco a ed wi h Ag nanopa icles bi e away bac e ia and chemiso b i uses. J Ma e Chem B. 2013;1(21):2701–9. [205]Cas o Mayo ga JL, Fab a Ro i a MJ, Cabedo Mas L, Sánchez Mo agas G, Laga ón Cabello JM. An imic obial nanocompo- si es and elec ospun coa ings based on poly (3‐hyd oxybu- y a e‐co‐3‐hyd oxy ale a e)and coppe oxide nanopa icles o ac i e packaging and coa ing applica ions. J Appl Polym Sci. 2018;135(2):45673. [206]Ba am‐Pin o D, Shukla S, Gedanken A, Sa id R. Inhibi ion o HSV‐1 a achmen , en y, and cell‐ o‐cell sp ead by unc io- nalized mul i alen gold nanopa icles. Small. 2010;6(9):1044–50. [207]Dunnill CW, Pa kin IP. Ni ogen-doped TiO 2 hin films: Pho oca aly ic applica ions o heal hca e en i onmen s. Dal on T ans. 2011;40(8):1635–40. [208]Go o o AO, Richa dson HH. Gene a ing hea wi h me al nanopa icles. Nano Today. 2007;2(1):30–8. [209]Bogdan J, Za zyńska J, Pławińska-Cza nak J. Compa ison o in ec ious agen s suscep ibili y o pho oca aly ic effec s o nanosized i anium and zinc oxides: A p ac ical app oach. Nanoscale Res Le . 2015;10(1):1–15. [210]Se ano-A oca Á, Takayama K, Tuñón-Molina A, Sey an M, Hassan SS, Pal Choudhu y P, e al. Ca bon-based nanoma- e ials: P omising an i i al agen s o comba COVID-19 in he mic obial- esis an e a. ACS nano. 2021;15(5):8069–86. [211]Same band M, Kal I, Gedanken A, Sa id R. He pes simplex i us ype-1 a achmen inhibi ion by unc ionalized g a- phene oxide. ACS Appl Ma e In e aces. 2014;6(2):1228–35. [212]Ye S, Shao K, Li Z, Guo N, Zuo Y, Li Q, e al. An i i al ac i i y o g aphene oxide: How sha p edged s uc u e and cha ge ma e . ACS Appl Ma e In e aces. 2015;7(38):21571–9. [213]Gholami MF, Laus e D, Ludwig K, S o m J, Ziem B, Se e in N, e al. Func ionalized g aphene as ex acellula ma ix mimics: Towa d well‐defined 2D nanoma e ials o mul i a- len i us in e ac ions. Ad Func Ma e . 2017;27(15):1606477. [214]Vaillan A. Nucleic acid polyme s: B oad spec um an i i al ac i i y, an i i al mechanisms and op imiza ion o he ea men o hepa i is B and hepa i is D in ec ion. An i i Res. 2016;133:32–40. [215]Tengdelius M, Lee C-J, G enegå d M, G iffi h M, Påhlsson P, Kon adsson P. Syn hesis and biological e alua ion o ucoidan-mime ic glycopolyme s h ough cyanoxyl-media ed ee- adical polyme iza ion. Biomac omolecules. 2014;15(7):2359–68. [216]Longa ela OL, Schmid TT, Schöneweis K, Romeo R, Wedemeye H, U ban S, e al. P o eoglycans ac as cellula hepa i is del a i us a achmen ecep o s. PLoS One. 2013;8(3):e58340. [217]Richa ds KF, Bienkowska-Haba M, Dasgup a J, Chen XS, Sapp M. Mul iple hepa an sul a e binding si e engagemen s a e equi ed o he in ec ious en y o human papilloma i us ype 16. J Vi ol. 2013;87(21):11426–37. [218]Ce quei a C, Liu Y, Kühling L, Chai W, Ha ezi W, an Kuppe el TH, e al. Hepa in inc eases he in ec i i y o Human Papilloma i us Type 16 independen o cell su ace p o eoglycans and induces L1 epi ope exposu e. Cell Mic obiol. 2013;15(11):1818–36. [219]Dey P, Be gmann T, Cuella -Camacho JL, Eh mann S, Chowdhu y MS, Zhang M, e al. Mul i alen flexible nanogels exhibi b oad-spec um an i i al ac i i y by blocking i us en y. ACS nano. 2018;12(7):6429–42. [220]Leibb and A, Meie C, König-Schus e M, Weinmüllne R, Kal hoffD, Pflug elde B, e al. Io a-ca ageenan is a po en inhi- bi o o influenza a i us in ec ion. PLoS One. 2010;5(12):e14320. [221]Buck CB, Thompson CD, Robe s JN, Mülle M, Lowy DR, Schille JT. Ca ageenan is a po en inhibi o o papilloma- i us in ec ion. PLoS Pa hog. 2006;2(7):e69. [222]Magnan S, To a J, El-Zein M, Bu chell A, Schille J, Fe enczy A, e al. Efficacy o a ca ageenan gel agains ansmission o ce ical HPV (CATCH): In e im analysis o a andomized, double-blind, placebo-con olled, phase 2B ial. Clin Mic obiol In ec . 2019;25(2):210–6. [223]Zheng M, Qu D, Wang H, Sun Z, Liu X, Chen J, e al. In anasal adminis a ion o chi osan agains influenza A (H7N9) i us in ec ion in a mouse model. Sci Rep. 2016;6:28729. 24 Ma jan Mo iei e al. [224]Kyluik DL, Su on TC, Le Y, Sco MD. Polyme -media ed b oad spec um an i i al p ophylaxis: U ili y in high isk en i onmen s. P og ess in molecula and en i onmen al bioenginee ing- om analysis and modeling o echnology applica ions. Rijeka: In ech; 2011. p. 167–190. [225]Cai X, P ominski A, Lin Y, Ankenb uck N, Rosenbe g J, Chen M, e al. A neu alizing an ibody-conjuga ed pho o- he mal nanopa icle cap u es and inac i a es SARS-CoV-2. bio xi . 2020. p. 11. [226]Rone MR, Ca ahe CE, Mille L, Mosca F, Slawek P, Haky JE, e al. O gano in Polyme s as An i i al Agen s Including Inhibi ion o Zika and Vaccinia Vi uses. J Ino g O ganome Polym Ma e . 2020;30(3):684–94. [227]Mo iei M, Kashanian S, Lucia LA, Khazaei M. In insic pa a- me e s o he syn hesis and uned p ope ies o amphiphilic chi osan d ug deli e y nanoca ie s. J Con olled Release. 2017;260:213–25. [228]Mo iei M, Abou alebi F, Fo ouzan a M, Do miani K, Nas - Es ahani MH, Mi ahmadi-Za e SZ. Sma co-deli e y o miR- 34a and cy o oxic pep ides (LTX-315 and meli in)by chi - osan based polyelec oly e nanoca ie s o specific cance cell dea h induc ion. Ma e Sci Eng C. 2021;128:112258. [229]Nie C, S ad mülle M, Yang H, Xia Y, WolffT, Cheng C, e al. Spiky nanos uc u es wi h geome y-ma ching opog aphy o i us inhibi ion. Nano Le . 2020;20(7):5367–75. [230]Hou YJ, Chiba S, Hal mann P, Eh e C, Ku oda M, Dinnon III KH, e al. SARS-CoV-2 D614G a ian exhibi s efficien eplica ion ex i o and ansmission in i o. Science. 2020;370(6523):1464–8. [231]Pu ohi R, Mi al A, Dalela S, Wa udka V, Pu ohi K, Pu ohi S. Social, en i onmen al and e hical impac s o nano echnology. Ma e Today P oc. 2017;4(4):5461–7. [232]Wes on S, Coleman CM, Haup R, Logue J, Ma hews K, Li Y, e al. B oad an i-co ona i us ac i i y o ood and d ug adminis a ion-app o ed d ugs agains SARS-CoV-2 in i o and SARS-CoV in i o. J Vi ol. 2020;94(21):e01218–20. [233]Tha ayil A, Rajakuma i R, Chi ayil CJ, Thomas S, Kala ikkal N A sho e iew on nano echnology in e en ions agains COVID-19. Eme gen Ma e . 2021;4(1):131–41. SARS-COV-2 and nano echnology 25