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

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.