The bat coronavirus RmYN02 is characterized by a 6-nucleotide deletion at the S1/S2 junction, and its claimed PAA insertion is highly doubtful

TL;DR

This study critically examines the RmYN02 strain, challenging claims of a natural PAA insertion at the S1/S2 junction of its spike protein, and finds it instead has a 6-nucleotide deletion, questioning the natural origin of SARS-CoV-2's furin cleavage site.

Contribution

The paper provides a detailed nucleotide-level analysis showing RmYN02 lacks the claimed insertion, offering a re-evaluation of the mutation's origin in SARS-CoV-2.

Findings

RmYN02 does not have an insertion at the S1/S2 junction.

The claimed PAA insertion is likely due to mutations.

SARS-CoV-2's 12-nucleotide insertion remains unique among related viruses.

Abstract

Zhou et al. reported the discovery of RmYN02, a strain closely related to SARS-CoV-2, which is claimed to contain a natural PAA amino acid insertion at the S1/S2 junction of the spike protein at the same position of the PRRA insertion that has created a polybasic furin cleavage site in SARS-CoV-2. The authors support with their findings the theory that the furin cleavage site insertion present in SARS-CoV-2 is natural. Because no nucleotide alignment with closely related strains of the region coding for the supposed insertion is provided by Zhou et al., we have applied several alignment algorithms to search for the most parsimonious alignments. We conclude that RmYN02 does not contain an insertion at the S1/S2 junction when compared to its closest relatives at the nucleotide level, but rather a 6-nucleotide deletion and that the claimed PAA insertion is more likely to be the result of mutations. A close examination of RmYN02 sequencing records and assembly methods is wishful. In conclusion, SARS-CoV-2, with its 12-nucleotide insertion at the S1/S2 junction remains unique among its sarbecovirus relatives.