Reviewing findings on the polypeptide sequence of the SARS-CoV-2 S-protein to discuss the origins of the virus

Abstract

Several investigations suggested origins of SARS-CoV-2 from the recombination of coronaviruses of various animals, including the bat Rhinolophus affinis and the pangolin Manis javanica, despite the processes describing the adaptation from a reservoir of animals to human are still debated. In this perspective, I will remark two main inconsistencies on the origins of SARS-CoV-2: polypeptide sequence alignment of the S-proteins does not return the expected identity of the receptor-binding motif among most of pangolin-CoVs and SARS-CoV-2; accurate referencing for samplings and sequencing deposition of the ancestral bat coronavirus named RaTG13 was missing since the first reports on the SARS-CoV-2 coronavirus. This contribution aims to stimulate discussion about the origins of SARS-CoV-2 and considers other intermediate hosts as a reservoir for coronavirus.

Keywords: RaTG13; S-protein; SARS-CoV-2; coronavirus; polypeptide sequence alignment; receptor-binding motif.

Figure 1.. Polypeptide sequence alignment.

(A) Alignment of the whole dataset of the S-proteins of SARS-CoV viruses. Respective names, accession numbers and additional information are reported in Table 1. Black rectangles: insertions -1 to -4, as reported by Zhou et al. [1] and Xiao et al. [5]. Red rectangle: S1/S2 cleavage site. Sequences were aligned using Muscle software [6]. Alignment accuracy was checked manually base by base using BioEdit v7.2.5 [7]. Part of the alignment not shown in this figure is indicated with: […]. (B) Alignment of the receptor-binding motif of the S-proteins of SARS-CoV-2, RaTG13 and of pangolin-CoVs. Blue rectangle: receptor-binding motif; black rectangles: positions of key amino acid residues involved in the interaction with human ACE2; red asterisk: additional key amino acid residue reported in Andersen et al. [8]; green circles: deposited sequences of pangolin-CoVs presenting a full asset of conserved key amino acid residues within the receptor-binding motif of SARS-CoV-2. If derived from the GISAID database (Table 1), S-protein sequences represented in this figure were predicted with orffinder (https://www.ncbi.nlm.nih.gov/orffinder/) using the deposited whole-genomes of their respective viruses as queries.