Functional alterations caused by mutations reflect evolutionary trends of SARS-CoV-2

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, has spread globally since late 2019.
• Early studies had limited data on viral evolution due to few available strains.
• Understanding SARS-CoV-2 mutations is crucial for tracking its evolutionary trajectory.

Purpose of the Study:

• To identify mutations in SARS-CoV-2 strains and analyze their functional consequences.
• To investigate the evolutionary trends of the SARS-CoV-2 genome.
• To determine the impact of mutations on viral infectivity and virulence.

Main Methods:

• Downloaded and analyzed 1809 SARS-CoV-2 genome sequences from GISAID (pre-April 2020).
• Aligned sequences to the reference genome (NC_045512) to identify nonsynonymous and synonymous mutations.
• Analyzed mutations for selection pressures (purifying and positive selection) and linkage disequilibrium.

Main Results:

• Identified 1017 nonsynonymous and 512 synonymous mutations; none in the spike protein's receptor-binding domain (RBD).
• Observed an average of 1.75 new mutations per strain per month.
• Five dominant mutations (3 nonsynonymous, 2 synonymous) were prevalent by April 2020, alongside two potential dominant nonsynonymous mutations.
• Functional analysis indicated decreased protein stability and reduced virulence, except for A23403G, which enhanced spike-ACE2 interaction and infectivity.

Conclusions:

• SARS-CoV-2 evolution shows a trend towards increased infectivity and decreased virulence.
• Dominant mutations significantly influence viral characteristics, including transmissibility.
• The A23403G mutation is a key driver of enhanced SARS-CoV-2 infectivity.