IN SILICO MOLECULAR DOCKING OF SMALL MOLECULES

AGAINST ZIKA VIRUS DRUG TARGETS

a, a, a
Sasivarman.N ,Saleem.S , Vishnu.S , Adam.Sb
a IV year B.Tech Biotechnology, Department of Biotechnology, Faculty of Engineering, Karpagam Academy
of Higher Education, Coimbatore - 641 021, Tamil Nadu, India.
b Assistant Professor, Department of Biotechnology, Karpagam Academy of Higher Education,

Coimbatore-641021, Tamil Nadu, India.

LIGAND SELECTION AND VALIDATION

Zika Virus ZIKV Lipinski rule
S.NO Ligand Name Mol. wt Log p H-Donor H-acceptor No of Rotatable Bond
(g/mol)

1 DMSO 78.0 0.86 0 1 0

• Zika fever is caused by Zika virus 2 Mycophenolic 320.0 2.7 2 6 6

• Zika virus (ZIKV) is spread by daytime-active Aedes

acid
3 Primaquine 259 2.7 3 4 6

mosquitoes, such as A. aegypti and A. albopictus. 4

5
Niclosamide 327 2.3 2 5 2

Amodiaquine 355.5 4.4 2 4 4

5K8T+SERTRALINE (-6.34 KJ /mol )
• ZIKA virus is related to the dengue, yellow 6 Sertraline 306.0 3.4 1 1 2

fever, Japanese encephalitis, and West Nile viruses. 7

8
Hippeastrine
Chloroquine
315
319.5
1.0
4.0
1
1
6
3
0
8
NS5 PROTEIN
9 Ivermectin 874.0 5.6 3 14 8

ADME properties
HIA Caco2 cell MDCK cell PPB
S.No Ligand name BBB CYP 2D6 (%) Permeability permeability (%)
(mm/sec) (mm/sec)

1 Ivermectin 0.22 Non 95.21 50.933 0.04 88.64

2 Mycophenolic Acid 0.01 Non 91.13 17.658 0.56 87.25

Niclosamide
5TMH+SERTRALINE(-7.89 KJ /mol)
3 0.09 Non 94.35 20.26 2.57 100.0

4 Sertraline 13.4 inhibitor 100.0 54.75 96.16 100

5 Chloroquine 7.73 Inhibitor 98.05 56.16 0,29 92.53

6 DMSO 0.64 Non 96.64 21.10 2.28 0.0

7 Ribovirin 0.15 Non 21.50 1.36 2.22 7.3

8 Primaquine 0.18 Inhibitor 93.88 32.94 127.12 57.66

9 Hippeastrine 0.64 Inhibitor 96.11 22.21 7.16 38.91

Flavivirus Life Cycle DOCKING RESULTS -AUTO DOCK) 5TMH+IVERMECTIN (-7.40 KJ /mol)

• The virus enters cells by receptor-mediated NS1 PROTEIN

endocytosis and fuses its membrane by an acidic-
pH-triggered mechanism in the endosome to release
the viral RNA.
• In this postfusion conformation, E adopts a hairpin-
like structure by the relocation of DIII and the
“zippering” of the stem along DII in the trimer,
resulting in the juxtaposition of the FL and the TM
helices in the fused membrane.
• They are transported through the exocytic
pathway of the cell until they reach the trans-
Golgi network (TGN).
5K6K + SERTRALINE(-7.57KJ/mol)
3D structure of NS1 (5K6K), NS3(5K8T), NS5(5TMH)
SUMMARY OF SEQUENCE ANALYSIS RESULT
5TMH+AMODIAQUINE (-7.07 KJ /mol)
5K6K + AMODIAQUINE(-7.62KJ/mol)
CONCLUSION:
These compounds were examined for their Pfizer's rule of
five and ADMET properties. Molecular docking was performed
between above inhibitors (ligands) and protein (NS1, NS3,
NS5) using Auto dock 1.5.6. Results revealed that the best fit
ligands against active site of NS1 (5K6K) were identified as
Amodiaquine(-7.63 kjmol-1) sertraline(-7.57 kjmol-1),
Azithromycin(-7.53 kjmol-1); NS3 (5K8T) were identified as
Niclosamide(-7.64 kjmol-1), Primaquine(-6.74 kjmol-1),
MycophenolicAcid(-6.71 kjmol-1); NS5 (5TMH) were
identified as Sertraline(-7.89 kjmol-1), Ivermectin(-7.40 kjmol-
1), Quinidine(-7.19 kjmol-1). The result of this computational
study proved that above small molecules shows drug-like
properties and strongly interacted with ZIKV-NS1, NS3 & NS5
protein. The docking analyses with NS1 (5K6K) revealed that
inhibitors
This approach therefore offers a new focus for Zika virus drug
development.
5K6K + IVERMECTIN(-7.08KJ/mol)
NS3 PROTEIN
REFERENCES:
de Lima Neto, D. F., Soares, A. P., Pour, S. Z., Ortiz, A. S.,
Freire, C. M., Neuhaus, P., ... & Zanotto, P. M. (2018).
Molecular dynamics suggests antiviral compounds active
against Dengue Virus show similar binding patterns to Zika
Virus proteins. bioRxiv, 309351.
Elfiky, A. A., & Elshemey, W. M. (2018). Molecular dynamics
simulation revealed binding of nucleotide inhibitors to ZIKV
polymerase over 444 nanoseconds. Journal of medical
5K8T+PRIMAQUINE (-6.74 KJ /mol) virology, 90(1), 13-18.
Esteves, E., Rosa, N., Correia, M. J., Arrais, J. P., & Barros, M.
(2017). New Targets for Zika Virus Determined by Human-
Viral Interactomic: A Bioinformatics Approach. BioMed
research international, 2017.
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5K8T+MYCOPHENOLIC ACID(-7.56 KJ /mol)