Mutations in membrane‐fusion subunit of spike glycoprotein play crucial role in the recent outbreak of COVID‐19

다국어 초록 (Multilingual Abstract)

Coronavirus disease‐2019 (COVID‐19), the ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a major threat to the entire human race. It is reported that SARS‐CoV‐2 seems to have relatively low pathogenicity and higher transmissibility than previously outbroke SARS‐CoV. To explore the reason of the increased transmissibility of SARS‐CoV‐2 compared with SARS‐CoV, we have performed a comparative analysis on the structural proteins (spike, envelope, membrane, and nucleoprotein) of two viruses. Our analysis revealed that extensive substitutions of hydrophobic to polar and charged amino acids in spike glycoproteins of SARS‐CoV2 creates an intrinsically disordered region (IDR) at the beginning of membrane‐fusion subunit and intrinsically disordered residues in fusion peptide. IDR provides a potential site for proteolysis by furin and enriched disordered residues facilitate prompt fusion of the SARS‐CoV2 with host membrane by recruiting molecular recognition features. Here, we have hypothesized that mutation‐driven accumulation of intrinsically disordered residues in spike glycoproteins play dual role in enhancing viral transmissibility than previous SARS‐coronavirus. These analyses may help in epidemic surveillance and preventive measures against COVID‐19.
Spike glycoprotein of SARS‐CoV2 experiences higher synonymous and non‐synonymous substitution rates than other three structural (E, M, N) proteins.
Extensive hydrophobic to polar and charged amino acid substitutions in S proteins during evolution from SARS‐CoV generate intrinsically disordered residues in the membrane fusion subunit (S2) of S protein.
Intrinsically disordered region at the beginning of S2 offers cleavage site of furin protease and by virtue of their flexible nature, they provide sensitive site for efficient proteolysis to activate the fusion peptide.
Enrichment of intrinsically disordered residues in fusion peptide prompts rapid fusion of viral envelop with host membrane by recruiting several MoRFs.
Intrinsic disorderness in spike glycoproteins in SARS‐CoV2 play dual role in enhancing their transmissibility than previous SARS‐corona virus.