An update on the origin of SARS‐CoV‐2: Despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O‐linked glycan residues

Abstract

The initial cases of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8 993 659 active cases, 469 587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS‐CoV‐2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS‐CoV‐2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 strains. The key residues of the receptor‐binding domain (RBD) and O‐linked glycan were compared. SARS‐CoV‐2 strains were clustered with RaTG13 (97.41% identity), Pangolin‐CoV (92.22% identity) and Bat‐SL‐CoV (80.36% identity), forms a new clade‐2 in lineage B of beta‐CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS‐CoV‐2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin‐CoV. SARS‐CoV‐2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O‐linked glycans were seen in RaTG13, suggesting that a detailed study needed in pangolin ( Manis javanica ) and bat ( Rhinolophus affinis ) related CoV.

Questions concerning the proximal origin of SARS‐CoV‐2

“…Andersen et al 1 documented the possible natural origin of SARS‐CoV‐2 from BatCoV RaTG13 2 . SARS‐CoV‐2 is the seventh zoonotic CoV virus capable of infecting humans, but the first and only human coronavirus (HCoV) with pandemic potential 3 .…”

“…HCoVs have high‐frequency “hot spots” for nonsynonymous amino acid replacements that can possibly create a positive selection for host tropism/adaptation, resistance to neutralizing antibodies, or immune evasion 2 . Interestingly, clinical SARS‐CoV‐2 isolates to date have only a single high‐frequency nonsynonymous mutation, D614G, in their S protein 9 .…”

Computational Analysis of SARS-CoV-2 and SARS-Like Coronavirus Diversity in Human, Bat and Pangolin Populations

“…The origin of SARS-CoV-2 is still unknown and a number of coronaviruses from different hosts have been proposed as the potential common ancestors [22,23]. However, bats are often linked to SARS-like viruses capable of zoonotic host transfer due to their unique niche as viral reservoirs.…”

New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

“…The outbreak started in mid-December 2019 in Wuhan, China [ 2 , 5 ]. Today, it is not possible to define with certainty the route taken by the virus to reach humans; but numerous assumptions agree with the animal origin [ 6 , 7 , 8 ]. Most likely, SARS-CoV-2 might have cryptically circulated within humans for years before being discovered [ 9 ].…”