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In Silico Identification of Nsp12 and Nsp13 as Potential Targets for Development of Broad-spectrum Antiviral Agents Against SARS-CoV, MERS-CoV, and 2019-nCoV (SARS-CoV-2)

Shengjie Dong, Jiachen Sun, Zhuo Mao, Yi-Lin Lu, Jie-Sen Li

2020

Abstract

Background2019 novel coronavirus (2019-nCoV) is officially named severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), and is a positive-sense, single-stranded RNA coronavirus. The virus is the pathogen of coronavirus disease 2019 (COVID-19) and is infectious through human-to-human transmission. The fact that 2019-nCoV is very close to SARS-CoV has been proved by several evidences, but there are significant differences between MERS-CoV and them. Therefore, in this work, we used MERS-CoV as a probe to find the homology proteins with conserved sequences among these three known human highly pathogenic coronaviruses.MethodsThe primary protein sequences of three viruses translated from the complete genome were downloaded from National Center for Biotechnology Information (NCBI). The sequence alignments of ORF1ab proteins of three viruses were done by using Clustal Omega. The assessments of the feasibility of homology modeling were performed by using SWISS-MODEL.ResultsHere, by using computational biology, we propose that four nonstructural proteins nsp12, nsp13, nsp14, and nsp16 exhibit considerable homology among SARS-CoV, MERS-CoV, and 2019-nCoV. Among them, nsp12 and nsp13 amino acid sequences are more conserved. Considering the crucial role of these two proteins in the process of virus invasion and pathological response, we first proposed these two proteins as priority targets to design new or screen existing broad-spectrum antiviral drugs. The high consistency…

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