High diversity in Delta variant across countries revealed by genome‐wide analysis of SARS‐CoV‐2 beyond the Spike protein

Abstract

The highly contagious Delta variant of SARS‐CoV‐2 has become a prevalent strain globally and poses a public health challenge around the world. While there has been extensive focus on understanding the amino acid mutations in the Delta variant’s Spike protein, the mutational landscape of the rest of the SARS‐CoV‐2 proteome (25 proteins) remains poorly understood. To this end, we performed a systematic analysis of mutations in all the SARS‐CoV‐2 proteins from nearly 2 million SARS‐CoV‐2 genomes from 176 countries/territories. Six highly prevalent missense mutations in the viral life cycle‐associated Membrane (I82T), Nucleocapsid (R203M, D377Y), NS3 (S26L), and NS7a (V82A, T120I) proteins are almost exclusive to the Delta variant compared to other variants of concern (mean prevalence across genomes: Delta = 99.74%, Alpha = 0.06%, Beta = 0.09%, and Gamma = 0.22%). Furthermore, we find that the Delta variant harbors a more diverse repertoire of mutations across countries compared to the previously dominant Alpha variant. Overall, our study underscores the high diversity of the Delta variant between countries and identifies a list of amino acid mutations in the Delta variant’s proteome for probing the mechanistic basis of pathogenic features such as high viral loads, high transmissibility, and reduced susceptibility against neutralization by vaccines.

Mutational insights among the structural proteins of SARS-CoV-2: frequencies and evolutionary trends in American countries

“…This is similar to previous studies indicating the I82T mutation as one of the most frequent mutations in the M protein in the USA, with a 116-fold increase from October 2020 to February 2021 [32]. Suratekar et al also reported I82T as one of the most prevalent mutations in the Delta variant in a systematic analysis of mutations from nearly 2 million SARS-CoV-2 genomes from 176 countries [33]. However, till 2020, D3G was reported as the most common mutation in this protein [22].…”

Dynamics of Viral Infection and Evolution of SARS-CoV-2 Variants in the Calabria Area of Southern Italy

“…It is of note that the different subtypes of the Delta variant present frequent relevant mutations also in proteins different from Spike such as I82T in the M protein, which is apparently specific of Delta (Suratekar et al, 2022 ). This mutation appeared in Italy in April 2021 and has risen to over 90% in December 2021.…”

“…The Omicron variant presents a large number of mutations, some of which have been reported in other VOCs such as S477N (B.1 variant); H69/V70 and P681H (Alpha variant); H655Y (Gamma variant); K417N (Beta variant and AY variants); T478K (Delta variant); A701V (Beta and Iota variants); and R346K (Mu variant) (Suratekar et al, 2022). A notable mutation identified in the genomes of Omicron sequenced in this study occurs in residue E484, a key player in immune escape (Laurini et al, 2021).…”

Limit of Detection for Rapid Antigen Testing of the SARS-CoV-2 Omicron and Delta Variants of Concern Using Live-Virus Culture

“…As of February 2022, the most recent SARS-CoV-2 strains declared variants of concern (VoC) by the U.S. Centers for Disease Control and Prevention are Omicron (strain B.1.1.529) and Delta (strain B.1.617.2) ( 7 ). Beyond striking amino acid mutations in the spike protein, Omicron also harbors P13L, Δ31–33, R203K, and G204R nucleocapsid mutations, while Delta strains carry D63G, R203M, and D377Y nucleocapsid mutations ( 8 , 9 ). However, the limits of detection (LoDs) of many FDA EUA antigen tests were established with gamma-irradiated or heat-inactivated preparations of the USA WA1/2020 (WA1) strain ( 10 ) lacking these nucleocapsid mutations.…”