Authors: Swargiary A
DOI: https://doi.org/10.21203/rs.3.rs-73308/v1
Abstract
Purpose: COVID-19, caused by SARS-CoV2 virus is a contagious disease affecting millions of lives
throughout the globe. Currently, there are no clinically approved drugs for SARS-CoV2 although some
drugs are undergoing clinical trials. The present study investigates the binding property of ivermectin on
four important drug targets, spike protein, RNA-dependent RNA polymerase, 3-chymotrypsin- and papainlike proteases of SARS-CoV2.
Methods: The 3D structure of ivermectin along with known antiviral drug lopinavir, simeprevir and four
nucleotides ATP, GTP, CTP, and UTP were downloaded from PubChem database. Crystal structures of
proteins were downloaded from PDB database. PDB files were converted into pdbqt file using AutoDock
tools. After proper processing and grid formation, docking was carried out in AutoDock vina. Furthermore,
the co-crystallized RNA and its binding interactions with RdRp were studied using various visualization
tools including Discovery studio.
Results: Docking study showed that ivermectin is the best binding drug compared to lopinavir and
simeprevir. The best binding interaction was found to be -9.7kcal/mol with RdRp suggesting potential
inhibitor of the protein. Twenty-one amino acid residues of RdRp were found to interact with ivermectin
including the catalytic residue Asp760. Furthermore, RNA-RdRp complex revealed that the catalytic active
residues Ser759 and Asp760 of RdRp formed strong interactions with RNA chain. Binding of ivermectin in
the active site of RdRp make clash with the nucleotides of RNA chain suggesting the possible inhibition
of replication.
Conclusions: The present study suggests ivermectin as a potential inhibitor of RdRp which may be crucial
to combat the SARS-CoV2.
Keywords: COVID-19, SARS-CoV2, ivermectin, RdRp, Docking
