Co esponding au ho : Shubhangi P Pa il
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion License 4.0.
Videoing B and i s S e eoisome s as Inhibi o s o Nipah Vi us- An In-silico S udy o
S uc u e-Based Vi ual Sc eening and Compa a i e ADMET P o iling
Kulsoom Bano Z Sayed, Deepa N Rangadal and Shubhangi P Pa il *
Depa men o Chemis y, The Ins i u e o Science, 15, Madam Cama Road, Man a Laya, Fo , Mumbai, Maha ash a
400032, India.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
Publica ion his o y: Recei ed on 06 Sep embe 2025; e ised on 26 Oc obe 2025; accep ed on 29 Oc obe 2025
A icle DOI: h ps://doi.o g/10.30574/gscbps.2025.33.1.0399
Abs ac
Nipah i us (NiV) can cause a pandemic. Since he e a e no e ec i e ea men s a ailable o NiV, he de elopmen o
d ugs equi es immedia e a en ion. In he con ex o d ug disco e y, na u al p oduc s ha e eme ged as a p omising
b anch wi h emendous scope. In his s udy, we sc eened 959 phy ochemicals om 10 Indian medicinal plan s using
he IMPPAT da abase, PyRx, P oTox 3.0, SwissADME and Au oDock 4. Videoin B (L2) bypassed all 7 sc eening le els. I s
s e eoisome ic o ms (1R,2R,4aS,6S,8aS)-2,5,5,8a- e ame hyl-5'-oxo-oc ahyd o-2H-spi o[naph halene-1,2'-oxolan]-6-
yl ace a e (L1) and (1S,2S,4aR,6R,8aR)-2,5,5,8a- e ame hyl-5'-oxo-oc ahyd o-2H-spi o[naph halene-1,2'-oxolan]-6-yl
ace a e (L3) we e ob ained om he LOTUS da abase. L1, L2 and L3 showed binding sco e o -6.7, -7.5 and -7.8 kcal/mol
espec i ely, be e han he s anda d- Riba i in (L0) when docked wi h he a achmen glycop o ein o NiV. The impac
o s e eoisome ism on inhibi o y ac ion, d ug-like p ope ies, ADMET p o iles, and oxicology was ho oughly examined
by using ADMETlab. Be e docking sco es, imp o ed pha macokine ics, medicinal p ope ies, ADMET p o iles and
educed oxici y conce ns sugges ha hese h ee na u al p oduc s- L1, L2 and L3 can be po en candida es o he
no el d ug disco e y o Ni . Hence, his s udy is a s ep owa ds pandemic p epa edness and aims o con ibu e o he
d ug de elopmen o deadly NiV.
Keywo ds: Nipah Vi us; In-Silico Analysis; S uc u e-Based Vi ual Sc eening; S e eoisome s; Docking; ADMET
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
345
G aphical Abs ac
1. In oduc ion
Nipah i us (NiV) belongs o genus henipa i us, amily Pa amyxo i idae and o de Mononega i uses (1–4). I is a highly
pa hogenic, zoono ic i us (5). I is en eloped, has nega i e-sense single-s anded RNA and is conside ed a pa hogen
co esponding o biosa e y le el 4, hence needing u mos ca e in labo a o y handling (2,6,7). P e opid ui ba s, also
called as lying oxes, a e p ima ily he na u al ese oi o NiV (2,6,8–12). Thei exc e a and sali a help in ansmi ing
he i us and causing disease o seconda y hos s/in e media e hos s (domes ic animals like pigs, goa s, ho ses, e c.),
which in u n sp ead in ec ion in humans when consumed (5,13). Humans and animals can de elop he disease by ea ing
ba -bi en da es o o he ui s. The i al en elope has he a achmen G and usion F p o ein esponsible o i s en y
in o he hos cell (11,14). B oad-spec um an i i als like Riba i in, Remdesi i and Fla ipi a i a e used in he
ea men o NiV (3,4,15). NiV in ec ions lead o in lamma ion o he b ain, causing encephali is and e en ually dea h
(2,15). Since i has high dea h a es, esea che s a e in despe a e sea ch o an e ec i e medica ion, o which na u al
p oduc s can u n ou o be a good op ion. In he con ex o d ug disco e y, his b anch has limi ed explo a ion and
emendous scope. Di ec lab explo a ion is immensely ime and esou ce-consuming; hence, in-silico app oaches a e
used o b idge his gap and sa e ime and esou ces.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
346
Figu e 1 Global impac and pe cen mo ali y a e o Ni
Coun ies in which NiV sp ead has been epo ed a e Malaysia, Singapo e, Philippines, India and Bangladesh (16–18).
Global impac has been shown in Fig. 1, which gi es he mo ali y a e om yea 1998 o 2023 o each coun y. The
i s ou b eak was in Malaysia in 1998 wi h a 40% mo ali y a e, ollowed by Singapo e in 1999 wi h a mo ali y a e
as low as 9%. Simila ly, he e was only one ou b eak in Philippines in 2014. Bangladesh had he maximum numbe o
cases wi h a conside ably high a ali y a e, almos e e y yea . India comes second in he lis , bu he ou b eak was no
obse ed egula ly, as seen in he case o Bangladesh. In 2021, India had a 100% mo ali y a e. In India, he i s
ou b eak was in Siligu i Ci y (Wes Bengal) in 2001 (1,6). The e a e 2 s ains o his i us- Bangladeshi and Malaysian,
he o me being mo e i ulen han he la e because i shows human- o-human ansmission and is ci cula ed in India
due o close geog aphical p oximi y. This i us is cu en ly es ic ed o ce ain egions, bu i is capable o causing a
pandemic (2).
Na u al p oduc s (NPs) and hei de i a i es show good esul s in clinical ials as e ec i e d ugs because hey exhibi
less oxici y as compa ed o syn he ic d ugs (19–21). Well-known an i-in lamma o y d ug ace ylsalicylic acid, de i ed
om Salix alba plan ’s ac i e componen , is one o he mos success ul d ugs ma ke ed (22,23). Ano he such example
is Colchicine om Colchicum au umnale, used o gou and a ious o he in lamma o y diseases (22,24). Fo COVID-19,
Vi o ee was epo ed o igh SARS-CoV-2 in ec ion (22). Fu he mo e, NPs used o COVID-19, like My ice in (25,26),
Punicalagin (26,27), Gallinamide A (26,28), ha e been epo ed. Few s udied phy ochemicals exhibi ing An i-HIV
ac i i y a e Daphneodo ins A & B (26,29), Kleinhospi ine E (26,30), Beesioside (26,31). An icance agen s ha e been
de eloped by he U.S. Na ional Cance Ins i u e wi h he help o NPs (32). Whe eas Bi uca iol (26,33), Kake omamide
(26,34), Halymeniaol (26,35) a e An i-mala ial agen s ob ained om plan s. A ew mo e epo ed compounds a e
Ubonodin (36), San ac uzama e A (26,37), Honaucin A (26,38,39). Au oma ion can ex ensi ely and apidly sc een as
chemical lib a ies i ually agains biological a ge s, speed up he d ug disco e y p ocedu es (22,39–42).
In he p esen esea ch, we aim o iden i y po en ial inhibi o s o he a achmen -G p o ein o NiV by i ually sc eening
959 phy ochemicals p esen in 10 Indian medicinal plan s, namely Pa ala (S e eospe mum sua eolens), Shalapa ni
(Desmodium gange icum), Mus a (Cype us o undus), Chi aya a (Swe ia chi a a), Guduchi (Tinospo a co di olia),
Bhunimba (And og aphis panicula a), Pa ha (Cissampelos pa ei a), Vasaka (Jus icia adha oda), Agniman ha
(Cle odend um phlomidis) and Ni gundi (Vi ex negundo). Vi edoin B and i s s e eoisome ic o ms- (1R,2R,4aS,6S,8aS)-
2,5,5,8a- e ame hyl-5'-oxo-oc ahyd o-2H-spi o[naph halene-1,2'-oxolan]-6-yl ace a e and (1S,2S,4aR,6R,8aR)-
2,5,5,8a- e ame hyl-5'-oxo-oc ahyd o-2H-spi o[naph halene-1,2'-oxolan]-6-yl ace a e we e ho oughly s udied o
analyse he impac o s e eoisome ism on inhibi ing ac i i y, binding a ini y, pha macokine ics, ADMET p o iles and
oxicology o all hese NiV a achmen glycop o ein-inhibi ing molecules.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
347
2. Me hods
2.1. P o ein s uc u e e ie al, quali y assessmen and s uc u al alida ion.
Wi h ca e ul conside a ion o a ious impo an pa ame e s, he bes s uc u e o a achmen glycop o ein o NiV came
ou o be 2VWD.
The s uc u e o he a achmen glycop o ein- G (2VWD) gi en in Fig. 2 was ob ained om RCSB PDB
(h ps://www. csb.o g/) P o ein Da a Bank, which is a well-known da abase con aining s uc u es o di e en p o eins
in di e en o ms (43–45). The s uc u e was downloaded in PDB o ma , a ailable amongs he a ious download
op ions. The PDB DOI o he chosen p o ein is h ps://doi.o g/10.2210/pdb2VWD/pdb. The 3D s uc u e e i ica ion
and quali y assessmen we e done using he ERRAT sco e (46), Ve i y3D (h ps://www.doe-mbi.ucla.edu/ e i y3d/)
(47) and Ramachand an plo om Disco e y S udio Visualize (48).
Figu e 2 3D s uc u e o he a achmen glycop o ein (PDB ID: 2VWD) o Ni a
2.2. S anda d & Ligands s uc u e e ie al.
Riba i in, a b oad-spec um an i i al, was aken as he s anda d. I s s uc u e was ob ained om he PubChem da abase
(h ps://PubChem.ncbi.nlm.nih.go /) managed by he U.S Na ional Ins i u es o Heal h (NIH) in SDF o ma , which was
la e con e ed o PDB and PDBQT o ma o docking. S uc u es o all phy ochemicals p esen in 10 Indian medicinal
plan s we e aken om he IMPPAT da abase (h ps://cb.imsc. es.in/imppa /). A simila s uc u e sea ch was done on
PubChem. S e eoisome ic s uc u es we e ob ained om he LOTUS da abase (h ps://lo us.na u alp oduc s.ne /)
(49). The molecula o mula o all h ee ligands is C19H30O4. Table 1 enlis s he PubChem ID/ LOTUS ID, canonical smiles
and he s uc u es o he s anda d and ligand.
2.3. Docking
Ini ially, he p o ein p epa a ion was done in UCSF Chime aX 1.8 by emo ing all non-s anda d esidues o emo e he
non-p o einous pa and adding missing a oms, pola hyd ogen and cha ges. Mul iple docking o all phy ochemicals
wi h he d uggable a ge (2VWD) was done in PyRx in 3 ba ches, ha ing a ied numbe s o ligands. La e , L0, L1, L2
and L3 we e docked wi h 2VWD in Au oDock 4 indi idually. A e docking, binding a ini ies o he bes binding pose
o he ligand we e abula ed in an Excel shee . The ou pu iles gene a ed con ained he binding a ini y o he op 9
poses, RMSD lowe and uppe bound and we e sa ed as CSV iles, which we e u he used o analysis.
2.4. ADMET P o iling
Ini ially, P oTox 3.0 (h ps:// ox.cha i e.de/p o ox3/) so wa e was used o know he oxici y classes o he
phy ochemicals and SwissADME (h p://www.swissadme.ch/) was used o check he ADME p o iles o he
phy ochemicals du ing he sc eening s age. L1, L2 and L3 showed be e binding sco es and ADMET p o iles han he
s anda d-L0. hence, de ailed ADMET- abso p ion, dis ibu ion, me abolism, exc e ion and oxici y p o iling o L1, L2 and
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
348
L3 was done in compa ison wi h L0 wi h he help o ADMETlab (h ps://adme mesh.scbdd.com/). ADMETlab ga e a
de ailed and comple e analysis o all ADMET pa ame e s(50).
Table 1 Ligands, hei s uc u es, IDs and canonical smiles
Ligand
Canonical Smiles
PubChem ID/
LOTUS ID
S uc u es
L0
Riba i in
(S anda d)
OC[C@H]1O[C@H]([C@@H]
([C@@H]1O)O) n1cnc(n1) C(=O)
N
37542
L1
(1R,2R,4aS,6S,8aS)-2,5,5,8a-
e ame hyl-5'-oxo-
oc ahyd o-2H-
spi o[naph halene-1,2'-
oxolan]-6-yl ace a e
CC(=O)O[C@H]1CC[C@@]2(C)[C
@@H](CC[C@@H](C)[C@]23CC
C(=O) O3) C1(C)C
Q105025374
L2
2,5,5,8a- e ame hyl-5'-oxo-
oc ahyd o-2H-
spi o[naph halene-1,2'-
oxolan]-6-yl ace a e
CC(=O)OC1CCC2(C)C(CCC(C)C23
CCC(=O) O3)C1(C)C
Q105025375
L3
(1S,2S,4aR,6R,8aR)-2,5,5,8a-
e ame hyl-5'-oxo-
oc ahyd o-2H-
spi o[naph halene-1,2'-
oxolan]-6-yl ace a e
CC(=O)O[C@@H]1CC[C@]2(C)[C
@H](CC[C@H](C)[C@@]23CCC(
=O) O3) C1(C)C
Q105025376
3. Resul s and Discussions
3.1. S uc u al alida ion and quali y assessmen o 2VWD
Ramachand an plo and Ve i y3D along wi h ERRAT sco e we e used o assess he o e all s uc u al quali y o he
p o ein(51,52). Fig. 3 shows he Ramachand an plo wi h a high majo i y o p o ein esidues in he mos a ou ed egion
indica ed by g een, which is a e y posi i e sign indica ing ha he p o ein’s s uc u e is ene ge ically s able and well-
de ined. Ve y ew poin s a e in ed, ha is he disallowed egion. Some o he esidues in his egion migh be accep able
i hey belong o lexible loops. The o e all quali y o he p o ein s uc u e is good as sugges ed by he Ramachand an
plo ob ained om Disco e y S udio Visualize .
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
349
Figu e 3 Ramachand an plo o he a achmen glycop o ein o NiV (PDB ID- 2VWD)
Ve i y3D plo is used o check i he 3D s uc u e o he p o ein complies wi h he 1D sequence and i he amino acid
esidues a e in an ene ge ically a ou ed en i onmen (48,53). Posi i e alues indica e a a ou able en i onmen ,
whe eas nega i e alues don’ . A la ge majo i y o he sco es o he esidues a e posi i e, as seen in Fig. 4, sugges ing
ha he o e all old o he p o ein shows consis ency wi h i s 1D sequence, meaning hey ha e a highe 3D-1D sco e.
Al hough he e a e ce ain dips below ze o, he o e all quali y o he p o ein s uc u e based on sequence is good since
80.92% o he amino acids ha e he same 3D en i onmen as sugges ed by he sequence, because hey sco ed abo e 0.1,
which is conside ed he h eshold o accep abili y. Thus, he e i y3D plo also sugges s ha he p o ein s uc u e mee s
he c i e ia o a good quali y p o ein and hence, can be aken ahead o u he s udies. Las ly, on ERRAT, he p o ein
s uc u e was un and he o e all quali y ac o o he p o ein s uc u e was 93.4949 ou o 100, indica ing e y high-
quali y p o ein.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
350
Figu e 4 Ve i y3D plo o chain A and B o he a achmen glycop o ein o NiV (PDB ID- 2VWD)
3.2. Vi ual Sc eening
Fo 10 Indian medicinal plan s, namely Pa ala (S e eospe mum sua eolens), Shalapa ni (Desmodium gange icum), Mus a
(Cype us o undus), Chi aya a (Swe ia chi a a), Guduchi (Tinospo a co di olia), Bhunimba (And og aphis panicula a),
Pa ha (Cissampelos pa ei a), Vasaka (Jus icia adha oda), Agniman ha (Cle odend um phlomidis) and Ni gundi (Vi ex
negundo), 959 phy ochemicals we e lis ed down om he IMPPAT da abase. Pos elimina ion o duplica es, 470
emained. Docking o all hese 470 phy ochemicals and he s anda d was done wi h he A achmen Glycop o ein
(2VWD) o Nipah i us. Resul s ob ained om docking showed ha ou o hese 470, 180 demons a ed be e binding
a ini y han he s anda d-Riba i in, which showed binding a ini y = -6.6 kcal/mol. The oxici y classes o all hese
compounds we e checked using P oTox-3.0 so wa e. Compounds wi h oxici y classes 5 and 6 we e sc eened ou . 32
such compounds we e ound, ou o which 27 we e blood-b ain ba ie pe mean , no a P-gap subs a e and we e d ug-
like. Only 2 did no inhibi he CYP450 enzymes. Las ly, only 1 compound, Videoin B (L2), complied wi h he o iginal
docking sco e on edocking indi idually, while he o he did no . These 7 le els o sc eening a e shown in Fig. 5. Hence,
o Vi edoin B simila s uc u e sea ch was done wi h he help o PubChem and LOTUS da abases, esul ing in he
selec ion o L1 and L3 as 2 non-plana s e eoisome s o L2
Figu e 5 Va ious s ages o Vi ual Sc eening o Ni Lead Compound disco e y
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
351
3.3. Docking esul s analysis
Figu e 6 Bes docked posed o L0, L1, L2 and L3 wi h p o ein 2VWD
3.3.1. Quan i a i e and compa a i e da a analysis o binding a ini ies
Table 2 enlis s he binding sco e, ype o in e ac ions be ween he ligand and he in e ac ing amino acid esidues and
he binding si e in which L0, L1, L2 and L3 a e p esen . Fig. 6 shows he ligands bound in he binding pocke s o he
p o ein-2VWD, an enla ged iew o he binding si e and he 2D diag am showing di e en in e ac ions p esen in he
p o ein-ligand complex o ma ion. L0 has a binding a ini y o - 6.6 kcal/mol. L1 has a binding a ini y - 6.7 kcal/mol.
The e is a di e ence o -0.1 uni s in he binding a ini ies o L0 and L1. L2 and L3 show signi ican ly highe nega i e
alues o binding a ini y han L0. L2 exhibi s -7.5 and L3 shows -7.8 kcal/mol.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
352
Table 2 Binding a ini ies, in e ac ion ypes and binding si e coo dina es o p o ein in complexa ion wi h L0, L1, L2
and L3
P o ein complexed wi h
Binding a ini y
(in kcal/mol)
Type o in e ac ions
Binding si e coo dina es
(x, y, z)
L0
-6.6
Un a ou able dono -dono
Van de Waals
Con en ional hyd ogen
Ca bon hyd ogen
Pi-ca ion
Pi-dono hyd ogen
Pi-alkyl
-47.006413,
-9.721968,
-24.949323
L1
-6.7
Van de Waals
Con en ional hyd ogen
-42.043783,
-1.941174,
-16.125174
L2
-7.5
Van de Waals
Con en ional hyd ogen
-14.592783,
-29.771478,
-25.868087
L3
-7.8
Van de Waals
Con en ional hyd ogen
Ca bon hyd ogen
-41.927783,
-1.905391,
-16.008435
3.3.2. S uc u al di e ences and hei impac
Figu e 7 Common 2D diag am o L1, L2 and L3 wi h s e eocen e s
Th ee impo an key pa ame e s a ec ing he binding a ini y a e plana i y, s e eochemis y and binding si e
coo dina es. As seen in Table 2, L1, L2 and L3 sha e he same molecula o mula C19H30O4 and he same a om
connec i i y, bu hey ha e di e en spa ial a angemen s. Since all s e eoisome s ha e di e en 3D diag ams bu sha e
he same 2D diag am, in Fig. 7, he Common 2D diag am o L1, L2, and L3 has been gi en wi h hei s e eocen e s
highligh ed in g een. The e a e 5 s e eocen e s o L1, L2 and L3 as men ioned in Table 3 and seen in Fig. 7. In L2, all
he g oups a he s e eocen e s lie in he plane o he pape , hence i demons a es a plana s uc u e, limi ing i s
in e ac ions o chain A o 2VWD. The 5 s e eocen e s in L1, L2, and L3 a e C-1, C-2, C-4a, C-6 and C-8a whe e C1 is he
spi o ca bon a om connec ing he naph halene ing o he oxolan ing; C2 is he ca bon a om bea ing he me hyl g oup
on he naph halene ing; C4a is he b idgehead ca bon a om p esen be ween he wo ings o he naph halene; C6 bea s
he ace a e g oup on he naph halene ing and C8a again is he b idgehead ca bon bu i bea s he me hyl g oup on he
naph halene ing. Fo L1, s e eochemis y is 1R,2R,4aS,6S,8aS as indica ed by he name o he compound in Table 1. I
1R becomes 1S, 2R becomes 2S, 4aS becomes 4aR, 6S becomes 6R and 8aS becomes 8aR, ha is, i he s e eochemis y
a he s e eocen e s o L1 is in e ed, he esul ing compound would be L3. The e o e, L1 and L3 a e non-plana
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
359
[4] Randhawa V, Pa hania S, Kuma M. Compu a ional Iden i ica ion o Po en ial Mul i a ge Inhibi o s o Nipah Vi us
by Molecula Docking and Molecula Dynamics. Mic oo ganisms. 2022 June 9;10(6):1181.
[5] Chan XHS, Haeusle IL, Choy BJK, Hassan MZ, Taka a J, Hu s TP, e al. The apeu ics o Nipah i us disease: a
sys ema ic e iew o suppo p io i isa ion o d ug candida es o clinical ials. Lance Mic obe. 2024
No ;101002.
[6] Paliwal S, Shinu S, Saha R. An eme ging zoono ic disease o be conce ned abou - a e iew o he nipah i us. J
Heal h Popul Nu . 2024 Oc 28;43(1):171.
[7] Tigabu B, Rasmussen L, Whi e EL, Towe N, Saeed M, Buk eye A, e al. A BSL-4 High-Th oughpu Sc een
Iden i ies Sul onamide Inhibi o s o Nipah Vi us. ASSAY D ug De Technol. 2014 Ap ;12(3):155–61.
[8] Halpin K, Hya AD, Foga y R, Middle on D, Bingham J, Eps ein JH, e al. P e opid Ba s a e Con i med as he
Rese oi Hos s o Henipa i uses: A Comp ehensi e Expe imen al S udy o Vi us T ansmission. Am Soc T op
Med Hyg. 2011 No 1;85(5):946–51.
[9] Howley PM, Knipe DM, edi o s. Fields i ology. Se en h edi ion. Philadelphia: Wol e s Kluwe ; 2021.
[10] Goldsmi h CS, Whis le T, Rollin PE, Ksiazek TG, Ro a PA, Bellini WJ, e al. Elucida ion o Nipah i us
mo phogenesis and eplica ion using ul as uc u al and molecula app oaches. Vi us Res. 2003 Ma ;92(1):89–
98.
[11] Tamin A, Ha cou BH, Ksiazek TG, Rollin PE, Bellini WJ, Ro a PA. Func ional P ope ies o he Fusion and
A achmen Glycop o eins o Nipah Vi us. Vi ology. 2002 Ap ;296(1):190–200.
[12] Cha u V, Kuma R, Kuma y S, Kajal F, Da id J. Nipah i us epidemic in sou he n India and emphasizing “One
Heal h” app oach o ensu e global heal h secu i y. J Fam Med P im Ca e. 2018;7(2):275.
[13] Chowdhu y S, Khan SU, C ame i G, Eps ein JH, B ode CC, Islam A, e al. Se ological E idence o Henipa i us
Exposu e in Ca le, Goa s and Pigs in Bangladesh. Geisbe T, edi o . PLoS Negl T op Dis. 2014 No
20;8(11):e3302.
[14] Ha cou BH, Tamin A, Ksiazek TG, Rollin PE, Ande son LJ, Bellini WJ, e al. Molecula Cha ac e iza ion o Nipah
Vi us, a Newly Eme gen Pa amyxo i us. Vi ology. 2000 June;271(2):334–49.
[15] Deb oy B, De A, Bha acha ya S, Pal K. In silico sc eening o he bal phy ochemicals o de elop a Rasayana o
immuni y agains Nipah i us. J Ayu eda In eg Med. 2023 No ;14(6):100825.
[16] N. Jag ap M, T. Bo ade P, V. Bodake S, B. Da eka A. Enhancing he science in he Global ansmission o Nipah
i us. Asian J Pha m Res. 2024 Sep 20;295–302.
[17] Tan FH, Suk i A, Id is N, Ong KC, Schee JP, Tan CT, e al. A sys ema ic e iew on Nipah i us: global molecula
epidemiology and medical coun e measu es de elopmen . Vi us E ol. 2024 Aug 7;10(1): eae048.
[18] Sa da M, Rehman SU, Younus M, Rizwan MA, Kaleem M, Ozaslan M. One Heal h app oach o Nipah i us
p e en ion. Vacunas. 2024 Ap ;25(2):264–73.
[19] Domingo-Fe nández D, Gadiya Y, P e o AJ, K e le CA, Mubeen S, Allen A, e al. Na u al P oduc s Ha e Inc eased
Ra es o Clinical T ial Success h oughou he D ug De elopmen P ocess. J Na P od. 2024 July 26;87(7):1844–
51.
[20] Sha ma N, Va ma V, Ve ma S. Plan -De i ed Compounds o Chemop e en ion and Chemo he apy: F om
Molecula Mechanisms o Clinical T ials. In: Geo ge B, edi o . Bioac i e Compounds om Medicinal Plan s o
Cance The apy and Chemop e en ion [In e ne ]. BENTHAM SCIENCE PUBLISHERS; 2024 [ci ed 2025 Jan 7]. p.
120–55. A ailable om: h ps://www.eu ekaselec .com/node/233812
[21] Elbadawi M, E e h T. In Vi o and Clinical S udies o Na u al P oduc s Ta ge ing he Hallma ks o Cance . In
Be lin, Heidelbe g: Sp inge Be lin Heidelbe g; 2024 [ci ed 2025 Jan 7]. (Handbook o Expe imen al
Pha macology). A ailable om: h ps://link.sp inge .com/10.1007/164_2024_716
[22] Ribei o-Filho J, Teles YCF, Igoli JO, Capasso R. Edi o ial: New ends in na u al p oduc esea ch o in lamma o y
and in ec ious diseases: Volume II. F on Pha macol. 2023 Jan 26;14:1144074.
[23] Fijałkowski Ł, Skubiszewska M, G ześk G, Koech FK, Nowaczyk A. Ace ylsalicylic Acid–P imus In e Pa es in
Pha macology. Molecules. 2022 Dec 1;27(23):8412.
[24] Dasgeb B, Ko n eich D, McGuinn K, Okon L, B ownell I, Sacke DL. Colchicine: an ancien d ug wi h no el
applica ions. B J De ma ol. 2018 Feb;178(2):350–6.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
360
[25] Su H, Yao S, Zhao W, Zhang Y, Liu J, Shao Q, e al. Iden i ica ion o py ogallol as a wa head in design o co alen
inhibi o s o he SARS-CoV-2 3CL p o ease. Na Commun. 2021 June 15;12(1):3623.
[26] Xu Z, Eichle B, Klausne EA, Du y-Ma zne J, Zheng W. Lead/D ug Disco e y om Na u al Resou ces. Molecules.
2022 No 28;27(23):8280.
[27] Du R, Coope L, Chen Z, Lee H, Rong L, Cui Q. Disco e y o chebulagic acid and punicalagin as no el allos e ic
inhibi o s o SARS-CoV-2 3CLp o. An i i al Res. 2021 June;190:105075.
[28] Ashhu s AS, Tang AH, Faj o á P, Yoon MC, Agga wal A, Bedding MJ, e al. Po en An i-SARS-CoV-2 Ac i i y by he
Na u al P oduc Gallinamide A and Analogues ia Inhibi ion o Ca hepsin L. J Med Chem. 2022 Feb
24;65(4):2956–70.
[29] O suki K, Li W, Asada Y, Chen CH, Lee KH, Koike K. Daphneodo ins A–C, An i-HIV Gnidimac in Rela ed Mac ocyclic
Daphnane O hoes e s om Daphne odo a. O g Le . 2020 Jan 3;22(1):11–5.
[30] Rahim A, Sai o Y, Miyake K, Go o M, Chen CH, Alam G, e al. Kleinhospi ine E and Cycloa ane T i e penoids om
Kleinho ia hospi a. J Na P od. 2018 July 27;81(7):1619–27.
[31] Wu H, Ma G, Yang Q, Zhu Y, Huang L, Tian Y, e al. Disco e y and syn hesis o no el beesioside I de i a i es wi h
po en an i-HIV ac i i y. Eu J Med Chem. 2019 Ma ;166:159–66.
[32] Jalil B, Rollinge JM, A anaso AG, Singla RK, Kingho n AD, Hein ich M. Co e publica ions in d ug disco e y and
na u al p oduc esea ch. F on Na P od. 2024 No 11;3:1493720.
[33] Smy nio opoulos V, Me en C, Kaise M, Tasdemi D. Bi u ca iol, a New An ip o ozoal Acyclic Di e pene om
he B own Alga Bi u ca ia bi u ca a. Ma D ugs. 2017 Aug 2;15(8):245.
[34] Sweeney-Jones A, Gaga ing K, An ono a-Koch J, Zhou H, Mojib N, Soapi K, e al. An imala ial Pep ide and
Polyke ide Na u al P oduc s om he Fijian Ma ine Cyanobac e ium Moo ea p oducens. Ma D ugs. 2020 Ma
18;18(3):167.
[35] Meesala S, Gu ung P, Ka modiya K, Sub ayan P, Wa e MG. Isola ion and s uc u e elucida ion o halymeniaol, a
new an imala ial s e ol de i a i e om he ed alga Halymenia lo esii. J Asian Na P od Res. 2018 Ap
3;20(4):391–8.
[36] Cheung-Lee WL, Pa y ME, Zong C, Ca agena AJ, Da s SA, Connell ND, e al. Disco e y o Ubonodin, an
An imic obial Lasso Pep ide Ac i e agains Membe s o he Bu kholde ia cepacia Complex. ChemBioChem. 2020
May 4;21(9):1335–40.
[37] Pa lik CM, Wong CYB, Ononye S, Lopez DD, Engene N, McPhail KL, e al. San ac uzama e A, a Po en and Selec i e
His one Deace ylase Inhibi o om he Panamanian Ma ine Cyanobac e ium c . Symploca sp. J Na P od. 2013
No 22;76(11):2026–33.
[38] Mascuch SJ, Boud eau PD, Ca land TM, Pie ce NT, Olson J, Hensle ME, e al. Ma ine Na u al P oduc Honaucin A
A enua es In lamma ion by Ac i a ing he N 2-ARE Pa hway. J Na P od. 2018 Ma 23;81(3):506–14.
[39] May LM, Bojanic D. No el ends in high- h oughpu sc eening. Cu Opin Pha macol. 2009 Oc ;9(5):580–8.
[40] Cox PB, Gup a R. Con empo a y Compu a ional Applica ions and Tools in D ug Disco e y. ACS Med Chem Le .
2022 July 14;13(7):1016–29.
[41] Wildey MJ, Haunso A, Tudo M, Webb M, Connick JH. High-Th oughpu Sc eening. In: Annual Repo s in Medicinal
Chemis y [In e ne ]. Else ie ; 2017 [ci ed 2025 Jan 4]. p. 149–95. A ailable om:
h ps://linkinghub.else ie .com/ e ie e/pii/S0065774317300076
[42] May LM, Fue s P. The Fu u e o High-Th oughpu Sc eening. SLAS Disco . 2008 July;13(6):443–8.
[43] Bu ley SK, Bha R, Bhikadiya C, Bi C, Bies e A, Biswas P, e al. Upda ed esou ces o explo ing expe imen ally-
de e mined PDB s uc u es and Compu ed S uc u e Models a he RCSB P o ein Da a Bank. Nucleic Acids Res.
2025 Jan 6;53(D1):D564–74.
[44] Za decki C, Du a S, Goodsell DS, Lowe R, Voig M, Bu ley SK. PDB -101: Educa ional esou ces suppo ing
molecula explo a ions h ough biology and medicine. P o ein Sci. 2022 Jan;31(1):129–40.
[45] Iwasa J, Goodsell DS, Bu ley SK, Za decki C. A new chap e o RCSB P o ein Da a Bank Molecule o he Mon h in
2025. S uc Dyn. 2025 Ma 1;12(2):021101.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
361
[46] Colo os C, Yea es TO. Ve i ica ion o p o ein s uc u es: Pa e ns o nonbonded a omic in e ac ions. P o ein Sci.
1993 Sep ;2(9):1511–9.
[47] Bowie JU, Lü hy R, Eisenbe g D. A Me hod o Iden i y P o ein Sequences Tha Fold in o a Known Th ee-
Dimensional S uc u e. Science. 1991 July 12;253(5016):164–70.
[48] Lü hy R, Bowie JU, Eisenbe g D. Assessmen o p o ein models wi h h ee-dimensional p o iles. Na u e. 1992
Ma ;356(6364):83–5.
[49] Ru z A, So okina M, Galgonek J, Mie chen D, Willighagen E, Gaud y A, e al. The LOTUS ini ia i e o open
knowledge managemen in na u al p oduc s esea ch. eLi e. 2022 May 26;11:e70780.
[50] Fu L, Shi S, Yi J, Wang N, He Y, Wu Z, e al. ADMETlab 3.0: an upda ed comp ehensi e online ADMET p edic ion
pla o m enhanced wi h b oade co e age, imp o ed pe o mance, API unc ionali y and decision suppo .
Nucleic Acids Res. 2024 July 5;52(W1):W422–31.
[51] Laskowski R, De Bee T. Ramachand an Plo . In: Hancock JM, Z elebil MJ, edi o s. Dic iona y o Bioin o ma ics
and Compu a ional Biology [In e ne ]. 1s ed. Wiley; 2004 [ci ed 2025 May 16]. A ailable om:
h ps://onlinelib a y.wiley.com/doi/10.1002/9780471650126.dob0603.pub2
[52] Zhou AQ, O’He n CS, Regan L. Re isi ing he Ramachand an plo om a new angle. P o ein Sci. 2011
July;20(7):1166–71.
[53] Eisenbe g D, Bowie JU, Lü hy R, Choe S. Th ee-dimensional p o iles o analysing p o ein sequence-s uc u e
ela ionships. Fa aday Discuss. 1992;(93):25–34.
[54] Singh S, Dash AK. Physical P ope ies, Thei De e mina ion, and Impo ance in Pha maceu ics. In: Pha maceu ics
[In e ne ]. Else ie ; 2024 [ci ed 2025 Ap 2]. p. 67–113. A ailable om:
h ps://linkinghub.else ie .com/ e ie e/pii/B9780323997966000023
[55] Lo sson T. Physicochemical P ope ies and Pha macokine ics. In: Essen ial Pha macokine ics [In e ne ].
Else ie ; 2015 [ci ed 2025 Ap 2]. p. 85–104. A ailable om:
h ps://linkinghub.else ie .com/ e ie e/pii/B9780128014110000032
[56] Kuma BRP, Soni M, Bhikhalal UB, Kakko IR, Jagadeesh M, Bommu P, e al. Analysis o physicochemical p ope ies
o d ugs om na u e. Med Chem Res. 2010 No ;19(8):984–92.
[57] Kenga MD, Howal RS, Aundhaka DB, Nikam AV, Hasabe PS. Physico-chemical P ope ies o Solid D ugs: A
Re iew. Asian J Pha m Technol. 2019;9(1):53.
[58] Alu H, Jain B, Dey S, Johns on TP, Jas i BR, Mi a AK. Physicochemical Fac o s A ec ing Biological Ac i i y. In:
Ghosh TK, Jas i BR, edi o s. Theo y and P ac ice o Con empo a y Pha maceu ics [In e ne ]. 1s ed. CRC P ess;
2021 [ci ed 2025 Ap 2]. p. 83–136. A ailable om:
h ps://www. aylo ancis.com/books/9781134441952/chap e s/10.1201/9780203644478-5
[59] Hageman M. P e o mula ion Designed o Enable Disco e y and Assess De elopabili y. Comb Chem High
Th oughpu Sc een. 2010 Feb 1;13(2):90–100.
[60] Ke ns EH, Di L. Rules o Rapid P ope y P o iling om S uc u e. In: D ug-like P ope ies: Concep s, S uc u e
Design and Me hods [In e ne ]. Else ie ; 2008 [ci ed 2025 Ap 2]. p. 37–42. A ailable om:
h ps://linkinghub.else ie .com/ e ie e/pii/B978012369520850005X
[61] Li B, Wang Z, Liu Z, Tao Y, Sha C, He M, e al. D ugMe ic: quan i a i e d ug-likeness sco ing based on chemical
space dis ance. B ie Bioin o m. 2024 May 23;25(4):bbae321.
[62] Guan L, Yang H, Cai Y, Sun L, Di P, Li W, e al. ADMET-sco e – a comp ehensi e sco ing unc ion o e alua ion o
chemical d ug-likeness. MedChemComm. 2019;10(1):148–57.
[63] Bene LZ. E ec o ou e o adminis a ion and dis ibu ion on d ug ac ion. J Pha macokine Biopha m. 1978
Dec;6(6):559–85.
[64] Alagga AA, Pelleg ini MV, Gup a V. D ug Abso p ion. In: S a Pea ls [In e ne ]. T easu e Island (FL): S a Pea ls
Publishing; 2025 [ci ed 2025 May 16]. A ailable om: h p://www.ncbi.nlm.nih.go /books/NBK557405/
[65] Be am-Ralph E, Ama e M. Fac o s a ec ing d ug abso p ion and dis ibu ion. Anaes h In ensi e Ca e Med. 2023
Ap ;24(4):221–7.
[66] Bohne T, Gan LS. Plasma p o ein binding: F om disco e y o de elopmen . J Pha m Sci. 2013 Sep ;102(9):2953–
94.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
362
[67] Zou P, Zheng N, Yang Y, Yu LX, Sun D. P edic ion o olume o dis ibu ion a s eady s a e in humans: compa ison
o di e en app oaches. Expe Opin D ug Me ab Toxicol. 2012 July;8(7):855–72.
[68] Tou ain PL, Bousque -Mélou A. Volumes o dis ibu ion. J Ve Pha macol The . 2004 Dec;27(6):441–53.
[69] Bohne T, Gan LS. Plasma p o ein binding: F om disco e y o de elopmen . J Pha m Sci. 2013 Sep ;102(9):2953–
94.
[70] Smi h DA, Di L, Ke ns EH. The e ec o plasma p o ein binding on in i o e icacy: misconcep ions in d ug
disco e y. Na Re D ug Disco . 2010 Dec;9(12):929–39.
[71] Zhao M, Ma J, Li M, Zhang Y, Jiang B, Zhao X, e al. Cy och ome P450 Enzymes and D ug Me abolism in Humans.
In J Mol Sci. 2021 No 26;22(23):12808.
[72] Remme H. The ole o he li e in d ug me abolism. Am J Med. 1970 No ;49(5):617–29.
[73] Almaz oo OA, Miah MK, Venka a amanan R. D ug Me abolism in he Li e . Clin Li e Dis. 2017 Feb;21(1):1–20.
[74] Sweeney BP, B omilow J. Li e enzyme induc ion and inhibi ion: implica ions o anaes hesia. Anaes hesia. 2006
Feb;61(2):159–77.
[75] Manikandan P, Nagini S. Cy och ome P450 S uc u e, Func ion and Clinical Signi icance: A Re iew. Cu D ug
Ta ge s [In e ne ]. 2018 Jan 5 [ci ed 2025 May 16];19(1). A ailable om:
h p://www.eu ekaselec .com/149505/a icle
[76] Daina A, Zoe e V. A BOILED-Egg To P edic Gas oin es inal Abso p ion and B ain Pene a ion o Small Molecules.
ChemMedChem. 2016 June 6;11(11):1117–21.
[77] Smi h DA, Beaumon K, Mau e TS, Di L. Clea ance in D ug Design: Minipe spec i e. J Med Chem. 2019 Ma
14;62(5):2245–55.
[78] Ho de GW, Gup a V. D ug Clea ance. In: S a Pea ls [In e ne ]. T easu e Island (FL): S a Pea ls Publishing; 2025
[ci ed 2025 May 16]. A ailable om: h p://www.ncbi.nlm.nih.go /books/NBK557758/
[79] Tou ain PL, Bousque -Mélou A. Plasma clea ance. J Ve Pha macol The . 2004 Dec;27(6):415–25.
[80] Ka zung BG, edi o . Basic & clinical pha macology. Fou een h edi ion. New Yo k: McG aw-Hill; 2018.
[81] Hahn RG, Lyons G. The hal -li e o in usion luids: An educa ional e iew. Eu J Anaes hesiol. 2016 July;33(7):475–
82.
[82] Cannizza o E, Cannizza o C, Plescia F, Ma ines F, Soleo L, Pi a E, e al. Exposu e o o o oxic agen s and hea ing
loss: A e iew o cu en knowledge. Hea Balance Commun. 2014 Dec;12(4):166–75.
[83] Je eczek-Fossa BA, Za owski A, Milani F, O ecchia R. Radio he apy-induced ea oxici y. Cance T ea Re . 2003
Oc ;29(5):417–30.
[84] Rybak LP, Ramkuma V. O o oxici y. Kidney In . 2007 Oc ;72(8):931–5.
[85] A an J. Cu en pe spec i es on inne ea oxici y. O ola yngol Neck Su g. 1995 Jan;112(1):133–44.
[86] Kopa al AT, Zey inoglu M. E ec s o Ca ac ol on a Human Non-Small Cell Lung Cance (NSCLC) Cell Line, A549.
Cy o echnology. 2003 No ;43(1–3):149–54.
[87] Xie J, Liu J, Liu H, Liang S, Lin M, Gu Y, e al. The an i umo e ec o anshinone IIA on an i-p oli e a ion and
dec easing VEGF/VEGFR2 exp ession on he human non-small cell lung cance A549 cell line. Ac a Pha m Sin B.
2015 No ;5(6):554–63.
[88] Choi SJ, Oh JM, Choy JH. Toxicological e ec s o ino ganic nanopa icles on human lung cance A549 cells. J Ino g
Biochem. 2009 Ma ;103(3):463–71.
[89] Yin X, Zhou J, Jie C, Xing D, Zhang Y. An icance ac i i y and mechanism o Scu ella ia ba ba a ex ac on human
lung cance cell line A549. Li e Sci. 2004 Sep ;75(18):2233–44.
[90] Foldbje g R, Dang DA, Au up H. Cy o oxici y and geno oxici y o sil e nanopa icles in he human lung cance
cell line, A549. A ch Toxicol. 2011 July;85(7):743–50.
[91] Wi chel HJ. D ug-induced hERG Block and Long QT Synd ome: hERG, d ugs, and LQTS. Ca dio asc The . 2011
Aug;29(4):251–9.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 344-363
363
[92] B own AM. hERG Block, QT Liabili y and Sudden Ca diac Dea h. In: Chadwick DJ, Goode J, edi o s. No a is
Founda ion Symposia [In e ne ]. 1s ed. Wiley; 2005 [ci ed 2025 May 16]. p. 118–35. A ailable om:
h ps://onlinelib a y.wiley.com/doi/10.1002/047002142X.ch10
[93] El-She i N, Tu i o G. The Long QT Synd ome and To sade De Poin es. Pacing Clin Elec ophysiol. 1999
Jan;22(1):91–110.
[94] Tisdale JE, edi o . To sades de poin es. London, Uni ed Kingdom: Academic P ess, an imp in o Else ie ; 2022.
360 p.
[95] Shah RR. D ug-Induced QT In e al P olonga ion—Regula o y Guidance and Pe spec i es on hERG Channel
S udies. In: Chadwick DJ, Goode J, edi o s. No a is Founda ion Symposia [In e ne ]. 1s ed. Wiley; 2005 [ci ed
2025 May 16]. p. 251–85. A ailable om: h ps://onlinelib a y.wiley.com/doi/10.1002/047002142X.ch19
[96] Tama go J. D ug-Induced To sade de Poin es: F om Molecula Biology o Bedside. Jpn J Pha macol.
2000;83(1):1–19.
[97] Fu uhama A, Sugiyama K ichi, Honma M. Ames mu agenici y o 15 a yl, benzyl, and alipha ic ing N-ni osamines.
Regul Toxicol Pha macol. 2025 Feb;156:105763.
[98] Thompson L, E ans J, Ma hews S. Ames o me : S a e-o - he-A Mu agenici y P edic ion wi h G aph
T ans o me s [In e ne ]. Chemis y; 2024 [ci ed 2025 May 16]. A ailable om:
h ps://chem xi .o g/engage/chem xi /a icle-de ails/67088b6bcec5d6c142d4098
[99] Guy RC. Ames es . In: Encyclopedia o Toxicology [In e ne ]. Else ie ; 2024 [ci ed 2025 May 16]. p. 377–9.
A ailable om: h ps://linkinghub.else ie .com/ e ie e/pii/B9780128243152011015
[100] Thompson L, E ans J, Ma hews S. Ames o me : a g aph ans o me neu al ne wo k o mu agenici y p edic ion
[In e ne ]. Chemis y; 2024 [ci ed 2025 May 16]. A ailable om:
h ps://chem xi .o g/engage/chem xi /a icle-de ails/66 d0cd5cec5d6c142e23a70
