Recognition of plausible therapeutic agents to combat COVID-19: An omics data based combined approach.

Mohammad Uzzal Hossain,Md Golam Mosaib,Muntahi Mourin,Keshob Chandra Das,Chaman Ara Keya,Md Tabassum Hossain Emon,Arittra Bhattacharjee,Md Salimullah,Zeshan Mahmud Chowdhury

doi:10.1016/j.gene.2020.145368

Abstract

Coronavirus disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has become an immense threat to global public health. In this study, we performed complete genome sequencing of a SARS-CoV-2 isolate.More than 67,000 genome sequences were further inspected from Global Initiative on Sharing All Influenza Data (GISAID). Using several in silico techniques, we proposed prospective therapeutics against this virus. Through meticulous analysis, several conserved and therapeutically suitable regions of SARS-CoV-2 such as RNA-dependent RNA polymerase (RdRp), Spike (S) and Membrane glycoprotein (M) coding genes were selected. Both S and M were chosen for the development of a chimeric vaccine that can generate memory B and T cells. siRNAs were also designed for S and M gene silencing. Moreover, six new drug candidates were suggested that might inhibit the activity of RdRp. Since SARS-CoV-2 and SARS-CoV-1 have 82.30% sequence identity, a Gene Expression Omnibus (GEO) dataset of Severe Acute Respiratory Syndrome (SARS) patients were analyzed. In this analysis, 13 immunoregulatory genes were found that can be used to develop type 1 interferon (IFN) based therapy. The proposed vaccine, siRNAs, drugs and IFN based analysis of this study will accelerate the development of new treatments.

Highlights

Coronavirus Disease–2019 (COVID–19) has drastically spread throughout the globe and become a massive threat to humanity[1]
Sixty seven (67) Severe Acute Respiratory Syndrome (SARS)-CoV-2 whole genome strains were collected from different countries (Supplementary Data 1)
The vaccine stimulated the differentiation of T helper Cell- 1 (Th 1) with certain level of T regulatory cell (Fig. 2E)

Summary

Introduction

Coronavirus Disease–2019 (COVID–19) has drastically spread throughout the globe and become a massive threat to humanity[1]. The quick prevention of COVID–19 is challenging because the causative agent of this disease is a novel Severe Acute Respiratory Syndrome (SARS) related Coronavirus (CoV) or SARS-CoV–2. This virus was totally unknown before the outbreak that took place in Wuhan, China; traditional development of therapeutics will not yield a rapid solution to control this pestilence 2,3. Coronavirinae has been divided into four categories such as Alpha, Beta, Gamm and Deltacoronavirus[4]. These pathogens were described as the “virology backwater” since very little was known about their virulence[5]. HCoV-OC43, HCoVHKU1, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) are members of Betacoronavirus[4]

Methods

Results

Discussion

Conclusion