Identification of best suitable repurposed drugs considering mutational spectra at RdRp (nsp12), 3CLpro (nsp 5) and PLpro (nsp 3) of SARS-CoV-2 in Indian population

Abstract

Background and Objective: COVID-19 originated in Wuhan, China and expanded to different geographical location of the world with variation in its sequence due to mutation, consequent alteration in different protein structures; resulting in different interaction with the host body. The highly infectious and diverge character of the virus makes it imperative to identify the promising inhibitory compounds for RdRp, 3CLpro and PLpro as suitable antiviral drug target so that viral duplication can be prevented in the host body.Methods: RdRp, 3CLpro and PLpro sequences of Indian patients were retrieved from the database and MSA was employed to identify mutation at nsp 3, nsp 5 and nsp 12. Protein structures were modeled considering all possible combination of sequences abundant in India and docking was performed with repurposed drugs, currently under trial for COVID-19, using Autodock Vina to find out the suitable ones considering the mutational spectra of SARS-CoV-2 in India.Results: PLpro is found to be most vulnerable to mutations with four mutations found in >5% studied population whereas in 3CLpro none observed at the frequency > 5%, so far. Two mutations were reported among Indian population (>5%) at RdRp. Therefore 3CLpro and RdRp were further analysed as a suitable target for repurposed drugs. Elbasvir has come up as the most suitable drug to inhibit the activity of RdRp in Indian population, followed by Remdesivir and Methylprednisolone. TMC 310911, Lopinavir and Elbasvir again, found to be the best candidates for inhibiting 3CLpro.Interpretation and Conclusions: Remdesivir and Lopinavir(alone or in combination with Ritonavir), the most popular drugs of choice at recent times may be suitable to be used in Indian population, considering the mutational variations in Indian population. Among others, Elbasvir, TMC 310911 and Methylprednisolone are good choices for treating COVID-19.

Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19 therapies

“…virtual screening of 50,000 chemical compounds from the CAS Antiviral COVID19 database against RdRP.35 They used a combination of 3D-similarity searches, docking, and 20 ns MDS to rank and select lead compounds and reported one compound (833463-19-7) that bound well to RdRP. Banerjee et al used protein modelling and computational docking techniques to investigate the effects of common mutations in RdRp, 3CLpro and PLpro sequences of Indian patients 36. …”