A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein

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. Recently, Zhou et al. [1] reported the discovery of a novel coronavirus strain RmYN02, which the authors claim 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 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

Emerging phylogenetic structure of the SARS-CoV-2 pandemic

“…SARS-CoV-2 is the seventh coronavirus to be identified infecting humans. The closest relatives (RaTG13 and RmYN02, 96% and 93% nucleotide identity respectively) derive from the Intermediate Horseshoe bat (Rhinolophus affinis) and the Malayan Horseshoe bat (Rhinolophus malayanus) 2 , although the original host is yet to be conclusively identified 3 . Since spilling over to humans, the virus has diverged rapidly, but it is unclear whether these mutations have resulted in SARS-CoV-2 lineages with different epidemiological and evolutionary characteristics [4][5][6][7][8][9] .…”

A path towards SARS-CoV-2 attenuation: metabolic pressure on CTP synthesis rules the virus evolution

“…This approach assumes that, after sufficient time of evolution, the nucleotides present at the majority of sites in the sequence have had chances to be modified several times reaching local saturation, so that it is difficult or impossible to link those with specific features of the proteins encoded in the virus (the beginning and end of the sequence, that are critical for RNA-dependent replication are not taken into account). By contrast, the presence of insertions or deletions (indels) will affect considerably the overall structure of the proteins, and this should impact their function in a way that is not likely to be reversible-see for example (79). An earlier such report (80) demonstrated the usefulness of this approach.…”

Genomic surveillance of a resurgence of COVID-19 in Guangzhou, China

“…With another nomenclature suggested by ref. 10 , 3 of 77 imported strains (3.9%) could be classi ed as lineage A that shared nucleotides at position 8782 (U) and 28144 (C) with the closest known bat virus RaTG13 6 , and 71 of 77 were from lineage B with different nucleotides (CU). Hereafter we adopted the lineage A/B nomenclature.…”

“…This is exempli ed by the whole genome sequence of the rst identi ed SARS-CoV-2 strain 2 . Thereafter, related coronavirus strains in bat and pangolin have been identi ed [3][4][5][6][7] . Over 18,700 genome sequences of SARS-CoV-2 strains have been shared by researchers worldwide in public databases such as GISAID 3 and GenBank.…”