Abstract
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. High adaptive plasticity on the spike protein of SASR-CoV-2 enables it to transmit across different host species. In the present study, we collected 2092 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny. We also analyzed the polymorphic interaction between spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 suggests that SARS-CoV-2 is probably originated from a recombination event on the spike protein between a bat coronavirus and a pangolin coronavirus that endows it humans infectivity. Compared with other regions in the S gene of SARS-CoV-2, the direct-binding sites of the receptor-binding domain (RBD) is more conserved. We focused on 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 and simulated their differential stability and binding affinity to hACE2 (S19-D615). The results indicate no preference for SARS-CoV-2 infectivity on people of different ethnic groups. The variants in the spike protein of SARS-CoV-2 may also be a good indicator demonstrating the transmission route of SARS-CoV-2 from its natural reservoir to human hosts.
Highlights
SARS-CoV-2 is a novel coronavirus causing the COVID-19 pandemic in 2020
The present study intends to (1) reconstruct the phylogeny of SARS-CoV-2 strains from different populations at the genomic level, (2) identify the variants on spike protein of SARS-CoV-2 based on the S gene sequences and predict their differential stability and the binding affinities to human angiotensin-converting enzyme 2 (ACE2) (hACE2), (3) explore the potential whether the variants in hACE2 from the different ethnic groups may affect the infectivity of SARS-CoV-2
2,112 genome sequences of beta coronaviruses derived from different hosts, with SARS-CoV and MERS-CoV selected as the out-groups (Fig. 1a)
Summary
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. The present study intends to (1) reconstruct the phylogeny of SARS-CoV-2 strains from different populations at the genomic level, (2) identify the variants on spike protein of SARS-CoV-2 based on the S gene sequences and predict their differential stability and the binding affinities to hACE2, (3) explore the potential whether the variants in hACE2 from the different ethnic groups may affect the infectivity of SARS-CoV-2. To this end, we analyzed the variants of ACE2 in a large cohort including 1000 Chinese people and other ethnic groups to identify the polymorphisms that may influence the binding of hACE2 and spike protein of SARS-CoV-2. Our study partially explains the origin of SARS-CoV-2 based on genomic and multiple key gene sequences, which allows us to elucidate the population risk profiles and help advance therapeutics such as a rationally designed soluble ACE2 receptor for the management of COVID-19
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