Abstract
The dire need of effective preventive measures and treatment approaches against SARS-CoV-2 virus, causing COVID-19 pandemic, calls for an in-depth understanding of its evolutionary dynamics with attention to specific geographic locations, since lockdown and social distancing to prevent the virus spread could lead to distinct localized dynamics of virus evolution within and between countries owing to different environmental and host-specific selection pressures. To decipher any correlation between SARS-CoV-2 evolution and its epidemiology in India, we studied the mutational diversity of spike glycoprotein, the key player for the attachment, fusion and entry of virus to the host cell. For this, we analyzed the sequences of 630 Indian isolates as available in GISAID database till June 07, 2020 (during the time-period before the start of Unlock 1.0 in India on and from June 08, 2020), and detected the spike protein variants to emerge from two major ancestors – Wuhan-Hu-1/2019 and its D614G variant. Average stability of the docked spike protein – host receptor (S-R) complexes for these variants correlated strongly (R 2 = 0.96) with the fatality rates across Indian states. However, while more than half of the variants were found unique to India, 67% of all variants showed lower stability of S-R complex than the respective ancestral variants, indicating a possible fitness loss in recently emerged variants, despite a continuous increase in mutation rate. These results conform to the sharply declining fatality rate countrywide (>7-fold during April 11 – June 28, 2020). Altogether, while we propose the potential of S-R complex stability to track disease severity, we urge an immediate need to explore if SARS-CoV-2 is approaching mutational meltdown in India.
Keywords: Molecular docking; Muller’s ratchet; Mutational meltdown; SARS-CoV-2; Viral evolutionary dynamics.
【저자키워드】 SARS-CoV-2, molecular docking, Muller's ratchet, Mutational meltdown, Viral evolutionary dynamics., 【초록키워드】 Evolution, Mutation, Epidemiology, lockdown, social distancing, COVID-19 pandemic, disease severity, Virus evolution, India, variant, spike glycoprotein, molecular docking, SARS-CoV-2 virus, virus, variants, Spike protein, stability, D614G variant, Wuhan, evolutionary dynamics, SARS-CoV-2 evolution, correlation, fusion, mutation rate, GISAID database, host cell, preventive measure, geographic locations, host receptor, sequences, virus spread, complex, attachment, sequence, Fatality rate, ancestor, treatment approaches, isolate, country, Prevent, effective, analyzed, unique, the spike protein, increase in, complexes, R 2, correlated strongly, declining, docked, Muller, treatment approach, 【제목키워드】 spike, Protein, Complete, Muller,