Screening of potent drug inhibitors against SARS-CoV-2 RNA polymerase: an in silico approach

Abstract

has emerged as a rapidly escalating serious global health issue, affecting every section of population in a detrimental way. Present situation invigorated researchers to look for potent targets, development as well as repurposing of conventional therapeutic drugs. NSP12, a RNA polymerase, is key player in viral RNA replication and, hence, viral multiplication. In our study, we have screened a battery of FDA-approved drugs against SARS-CoV-2 RNA polymerase using in silico molecular docking approach. Identification of potent inhibitors against SARS-CoV-2 NSP12 (RNA polymerase) were screeened from FDA approved drugs by virtual screening for therapeutic applications in treatment of COVID-19. In this study, virtual screening of 1749 antiviral drugs was executed using AutoDock Vina in PyRx software. Binding affinities between NSP12 and drug molecules were determined using Ligplot + and PyMOL was used for visualization of docking between interacting residues. Screening of 1749 compounds resulted in 14 compounds that rendered high binding affinity for NSP12 target molecule. Out of 14 compounds, 5 compounds which include 3a (Paritaprevir), 3d (Glecaprevir), 3h (Velpatasvir), 3j (Remdesivir) and 3l (Ribavirin) had a binding affinity of − 10.2 kcal/mol, −9.6 kcal/mol, − 8.5 kcal/mol, − 8.0 kcal/mol and − 6.8 kcal/mol, respectively. Moreover, a number of hydrophobic interactions and hydrogen bonding between these 5 compounds and NSP12 active site were observed. Further, 3l (Ribavirin) was docked with 6M71 and molecular dynamic simulation of the complex was also performed to check the stability of the conformation. In silico analysis postulated the potential of conventional antiviral drugs in treatment of COVID-19. However, these finding may be further supported by experimental data for its possible clinical application in present scenario.

Virtual screening of substances used in the treatment of SARS-CoV-2 infection and analysis of compounds with known action on structurally similar proteins from other viruses

“… 7BV2 AutoDock Vina, Glide, rDock GROMACS 1615 FDA-approved drugs, ZINC database Leucal, Natamycin, Folic Acid [101] 7BW4 DockThor, Autodock Vina, PatchDock GROMACS 48 antivirals Ribavirin, Zanamivir, Penciclovir [141] 6M71 AutoDock Vina GROMACS 92 phytochemicals Hesperidin, Rutin, Quercetin [69] 7BTF AutoDock Vina NAMD VMD Novel adenosine derivatives 4 unamed adenosine derivates [142] 6M71 Autodock 4.0.1. - 65 FDA approved small molecule Raltegravir, Indinavir, Tipranavir, Dolutegravir, Etravirine [143] 6M71 Moe-Dock GROMACS 63 anti-viral drugs approved by the FDA Ledipasvir, Remdesivir, Paritaprevir [144] 6M71 AutoDock Vina - Flavonoids, phenolic acids, and terpenes p-Coumaric Acid, Ellagic Acid, Kaempferol, Quercetin [145] 6M71 Discovery studio Desmond Zinc15 DataBank Paritaprevir, Glecaprevir, Velpatasvir, Remdesivir, Ribavirin [146] …”

An Updated Review of Computer-Aided Drug Design and Its Application to COVID-19

“…Furthermore, the antiviral mechanisms of these drugs (remdesivir, lopinavir/ritonavir, and chloroquine/hydroxychloroquine) against SARS-CoV-2 have been thoroughly reviewed by Uzunova et al (2020) [160]. performed docking-based virtual screening from a library of 1764 antiviral drugs against SARS-CoV-2 NSP12 (RNA polymerase) and identified five compounds, viz., paritaprevir, glecaprevir, velpatasvir, remdesivir, and ribavirin which exhibited high-binding affinity with the drug target [161]. Gowrishankar et al (2021) screened a total of 57 phytochemicals from three most commonly used Indian herbs (Justicia adhatoda, Eucalyptus globulus, and Vitex negundo) used in "steam inhalation therapy" against four structural protein targets of SARS-CoV-2 viz.…”

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

“…In silico drug design and discovery of RdRp inhibitors are given in Table 7. In addition to remdesivir and ribavirin, the molecular docking study of 1,749 antiviral drugs suggested that paritaprevir, glecaprevir, and velpatasvir also showed interesting interactions with RdRp (Singh et al, 2021). The top 50 compounds retrieved from structure-based virtual screening of 15,220 compounds from DrugBank and TargetMol Bioactive compounds Library against SARS-CoV-2 RdRp were evaluated by bio-layer interferometry (BLI) binding followed by cell-based polymerase activity assays .…”