Genomic Feature Analysis of Betacoronavirus Provides Insights Into SARS and COVID-19 Pandemics.

Xin Li,Qiang Zhao,Shunmei Chen,Guangyou Duan,Shan Gao,Zhangyong Hong,Jishou Ruan,Tung On Yau,Jia Chang,Liangge Wang

doi:10.3389/fmicb.2021.614494

Abstract

In December 2019, the world awoke to a new betacoronavirus strain named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Betacoronavirus consists of A, B, C and D subgroups. Both SARS-CoV and SARS-CoV-2 belong to betacoronavirus subgroup B. In the present study, we divided betacoronavirus subgroup B into the SARS1 and SARS2 classes by six key insertions and deletions (InDels) in betacoronavirus genomes, and identified a recently detected betacoronavirus strains RmYN02 as a recombinant strain across the SARS1 and SARS2 classes, which has potential to generate a new strain with similar risk as SARS-CoV and SARS-CoV-2. By analyzing genomic features of betacoronavirus, we concluded: (1) the jumping transcription and recombination of CoVs share the same molecular mechanism, which inevitably causes CoV outbreaks; (2) recombination, receptor binding abilities, junction furin cleavage sites (FCSs), first hairpins and ORF8s are main factors contributing to extraordinary transmission, virulence and host adaptability of betacoronavirus; and (3) the strong recombination ability of CoVs integrated other main factors to generate multiple recombinant strains, two of which evolved into SARS-CoV and SARS-CoV-2, resulting in the SARS and COVID-19 pandemics. As the most important genomic features of SARS-CoV and SARS-CoV-2, an enhanced ORF8 and a novel junction FCS, respectively, are indispensable clues for future studies of their origin and evolution. The WIV1 strain without the enhanced ORF8 and the RaTG13 strain without the junction FCS “RRAR” may contribute to, but are not the immediate ancestors of SARS-CoV and SARS-CoV-2, respectively.

Highlights

A new betacoronavirus strain named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 (Hassan et al, 2020a,b; Lundstrom et al, 2020; Seyran et al, 2020)
These results suggested that recombination, rather than accumulated mutations had triggered crossspecies transmission and outbreaks of SARS-CoV and SARSCoV-2
Recombination, receptor binding abilities, junction furin cleavage sites (FCSs), first hairpins and open reading frame 8 (ORF8) are main factors contributing to extraordinary transmission, virulence and host adaptability of betacoronavirus

Summary

Introduction

A new betacoronavirus strain named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 (Hassan et al, 2020a,b; Lundstrom et al, 2020; Seyran et al, 2020). Since SARS-CoV-2 is highly similar to SARS-CoV, many studies have focused on the investigation of the receptor binding domain (RBD) of the Spike (S) protein and its receptor angiotensin-converting enzyme 2 (ACE2) using the same strategies and methods as in SARS-CoV (Graham and Baric, 2010) Different from these studies, we previously reported several other findings on SARS-CoV-2 for the first time, including the following in particular: (1) the alternative translation of Nankai coding sequence (Nankai CDS) that characterize the rapid mutation rate of betacoronavirus at the nucleotide level (Chen et al, 2020); (2) a furin cleavage site (FCS) "RRAR" in the junction region between S1 and S2 subunits (junction FCS) of SARS-CoV-2 that may increase the efficiency of viral entry into cells (Li et al, 2020); and (3) the use of 5 untranslated-region (UTR) barcoding for the detection, identification, classification and phylogenetic analysis of—though not limited to—CoVs (Duan et al, 2020). The jumping transcription and recombination of CoVs share the same molecular mechanism (Li et al, 2021), which inevitably causes CoV outbreaks

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Conclusion