Emerging mutation patterns in SARS-CoV-2 variants

https://doi.org/10.1016/j.bbrc.2021.11.059Get rights and content

Highlights

  • Important patterns of mutations in SARS-CoV-2 are emerging in variants of concern.

  • The majority of distinguishing mutations in variants of concern alter the NTD of the SARS-CoV-2 spike protein.

  • Mutations in the NTD accumulate at sites of high flexibility in the SARS-CoV-2 spike protein.

  • A transmissibility mutation pattern corresponds with interchain contacts in the spike protein trimer.

  • Emerging variants exhibit mutations with the same patterns as variants of concern, indicating progression.

Abstract

There is an urgent need to understand the functional effects of mutations in emerging variants of SARS-CoV-2. Variants of concern (alpha, beta, gamma and delta) acquired four patterns of spike glycoprotein mutations that enhance transmissibility and immune evasion: 1) mutations in the N-terminal domain (NTD), 2) mutations in the Receptor Binding Domain (RBD), 3) mutations at interchain contacts of the spike trimer, and 4) furin cleavage site mutations. Most distinguishing mutations among variants of concern are exhibited in the NTD, localized to sites of high structural flexibility. Emerging variants of interest such as mu, lambda and C.1.2 exhibit the same patterns of mutations as variants of concern. There is a strong likelihood that SARS-CoV-2 variants will continue to emerge with mutations in these defined patterns, thus providing a basis for the development of next line antiviral drugs and vaccine candidates.

Keywords

SARS-CoV-2
COVID
Mutations
Transmissibility
Immune evasion

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