Global SNP analysis of 11,183 SARS‐CoV‐2 strains reveals high genetic diversity

Abstract

Since first identified in December of 2019, COVID‐19 has been quickly spreading to the world in few months and COVID‐19 cases are still undergoing rapid surge in most countries worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), adapts and evolves rapidly in nature. With the availability of 16,092 SARS‐CoV‐2 full genomes in GISAID as of 13 May, we removed the poor‐quality genomes and performed mutational profiling analysis for the remaining 11,183 viral genomes. Global analysis of all sequences identified all single nucleotide polymorphisms (SNPs) across the whole genome and critical SNPs with high mutation frequency that contributes to five‐clade classification of global strains. A total of 119 SNPs were found with 74 non‐synonymous mutations, 43 synonymous mutations and two mutations in intergenic regions. Analysis of geographic pattern of mutational profiling for the whole genome reveals differences between each continent. A transition mutation from C to T represents the most mutation types across the genome, suggesting rapid evolution and adaptation of the virus in host. Amino acid (AA) deletions and insertions found across the genome results in changes in viral protein length and potential function alteration. Mutational profiling for each gene was analysed, and results show that nucleocapsid gene demonstrates the highest mutational frequency, followed by Nsp2, Nsp3 and Spike gene. We further focused on non‐synonymous mutational distributions on four key viral proteins, spike with 75 mutations, RNA‐dependent‐RNA‐polymerase with 41 mutations, 3C‐like protease with 22 mutations and Papain‐like protease with 10 mutations. Results show that non‐synonymous mutations on critical sites of these four proteins pose great challenge for development of anti‐viral drugs and other countering measures. Overall, this study provides more understanding of genetic diversity/variability of SARS‐CoV‐2 and insights for development of anti‐viral therapeutics.

SARS-CoV-2 main protease suppresses type I interferon production by preventing nuclear translocation of phosphorylated IRF3

“…Notably, the catalytic site residues Cys144 and His41 as well as the Y-X-H motif in NSP5 are highly conserved among all strains of SARS-CoV and SARS-CoV-2. G15S and K90R are two common polymorphic variants of SARS-CoV-2 NSP5 in circulating strains of SARS-CoV-2 [33,34].…”

“…Up to date, 22 non-synonymous substitutions in NSP5 have been discovered in circulating strains of SARS-CoV-2 [33]. The non-catalytic region of NSP5 is apparently divergent.…”

“…To determine whether the non-synonymous substitutions might affect type I IFN antagonism of SARS-CoV-2 NSP5, we created its G15S and K90R variants. These two variants were chosen for further analysis since they are frequently seen in circulating strains of SARS-CoV-2 [33,34]. Whereas the G15S variant is common in European strains, the K90R variant is more frequently found in Chinese and Icelandic strains [33].…”

Determinants of SARS-CoV-2 transmission to guide vaccination strategy in an urban area

“…The COVID-19 pandemic has affected the lives of billions of people globally. Efforts to understand the transmission of SARS-CoV-2 have been undertaken at different scales including at global level 1–3 , across continents (Europe and North America 4 ), and within countries (such as Austria 5 , Brazil 6 , France 7 , Iceland 8 , South Africa 9 , and Thailand 10 ). The ultimate goal of COVID-19 molecular epidemiological studies is to understand and contain the pandemic.…”

“…Efforts to understand transmission of SARS-CoV-2 have been undertaken at different scales including at a global level 1–3 , across continents (Europe and North America 4 ), within countries (Austria 5 , Brazil 6 , France 7 , Iceland 8 , South Africa 9 , Thailand 10 ) and in large cities (Beijing 11 , Boston 12 , Houston 13 , and New York City 14–16 ). In Europe, ∼ 30% of the population live in small urban areas (10 k − 300 k inhabitants) 17 , which accordingly play a major role in SARS-CoV-2 transmission yet have not been studied.…”