Abstract
Viruses from the Coronaviridae family have been reported to infect a large range of hosts, including humans. The latest human-infecting coronavirus, SARS-CoV-2, turned into a pandemic and subtypes with different transmissibility have appeared since then. The SARS-CoV-2 Spike (S) protein interacts with the angiotensin-converting enzyme 2 (ACE2) host receptor, and thus, in silico models, based on the structural features of the SARS-CoV-2 S protein-ACE2 receptor complex, as well as ACE2 amino acid patterns, may be used to predict the within- and between-species transmissibility of SARS-CoV-2 subtypes. Here, it is shown that at the beginning of the pandemic, the SARS-CoV-2 S protein was, as expected for a virus that just jumped the species barrier, ill-adapted to the human ACE2 receptor, and that the replacement of one SARS-CoV-2 variant by another is partially due to a better fitting of the S protein-human ACE2 complex. Moreover, it is shown that mutations that are predicted to lead to a better fit have increased in the population due to positive selection. It is also shown that the number of ACE2-interfacing residues is positively correlated with the transmissibility rate of SARS-CoV-2 variants. Finally, it is shown that the number of species that are susceptible to infection by SARS-CoV-2, and that could be a reservoir for this virus, is likely higher than previously thought.
Keywords: Coronaviridae; SARS-CoV-2; angiotensin converting enzyme 2 (ACE2); interfacing residues; prediction model; spike glycoprotein (S).
【저자키워드】 SARS-CoV-2, Prediction model, Coronaviridae, Angiotensin converting enzyme 2 (ACE2), interfacing residues, spike glycoprotein (S)., 【초록키워드】 ACE2, coronavirus, pandemic, Mutation, S protein, spike, Positive selection, angiotensin converting enzyme 2, spike glycoprotein, SARS-CoV-2 variant, Infection, in silico, virus, angiotensin-converting enzyme 2, angiotensin converting enzyme, Protein, Transmissibility, SARS-CoV-2 variants, humans, Coronaviridae, predict, SARS-CoV-2 S protein, Angiotensin-converting enzyme, Amino acid, angiotensin, Subtypes, enzyme, host receptor, species, complex, residue, hosts, Coronaviridae family, human ACE2 receptor, residues, replacement, reservoir, transmissibility of SARS-CoV-2, subtype, infect, receptor complex, susceptible, feature, thought, shown, predicted, reported, interact, expected, the Coronaviridae, positively correlated, the SARS-CoV-2, 【제목키워드】 Model,