Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load


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Eskier D., SUNER KARAKÜLAH A., OKTAY Y., KARAKÜLAH G.

PEERJ, cilt.8, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8
  • Basım Tarihi: 2020
  • Doi Numarası: 10.7717/peerj.10181
  • Dergi Adı: PEERJ
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: SARS-CoV-2, COVID-19, nsp14, 3 '-5 ' exonuclease, RNA-dependent RNA polymerase, RdRp, Mutation rate
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

SARS-CoV-2 is a betacoronavirus responsible for COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load without selective pressure and across the genome, compared to nsp7, nsp8 and nsp12, which form the core polymerase complex. We propose nsp14 as a priority research target for understanding genomic variance rate in SARS-CoV-2 isolates and nsp14 mutations as potential predictors for high mutability strains.