PeerJ (Mar 2022)

An issue of concern: unique truncated ORF8 protein variants of SARS-CoV-2

  • Sk. Sarif Hassan,
  • Vaishnavi Kodakandla,
  • Elrashdy M. Redwan,
  • Kenneth Lundstrom,
  • Pabitra Pal Choudhury,
  • Tarek Mohamed Abd El-Aziz,
  • Kazuo Takayama,
  • Ramesh Kandimalla,
  • Amos Lal,
  • Ángel Serrano-Aroca,
  • Gajendra Kumar Azad,
  • Alaa A.A. Aljabali,
  • Giorgio Palù,
  • Gaurav Chauhan,
  • Parise Adadi,
  • Murtaza Tambuwala,
  • Adam M. Brufsky,
  • Wagner Baetas-da-Cruz,
  • Debmalya Barh,
  • Vasco Azevedo,
  • Nikolas G. Bazan,
  • Bruno Silva Andrade,
  • Raner José Santana Silva,
  • Vladimir N. Uversky

DOI
https://doi.org/10.7717/peerj.13136
Journal volume & issue
Vol. 10
p. e13136

Abstract

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Open reading frame 8 (ORF8) shows one of the highest levels of variability among accessory proteins in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19). It was previously reported that the ORF8 protein inhibits the presentation of viral antigens by the major histocompatibility complex class I (MHC-I), which interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 in evading immunity and plays a role in SARS-CoV-2 replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein, defines the B.1.1.7 lineage of SARS-CoV-2, engendering the second wave of COVID-19. In the present study, 47 unique truncated ORF8 proteins (T-ORF8) with the Q27STOP mutations were identified among 49,055 available B.1.1.7 SARS-CoV-2 sequences. The results show that only one of the 47 T-ORF8 variants spread to over 57 geo-locations in North America, and other continents, which include Africa, Asia, Europe and South America. Based on various quantitative features, such as amino acid homology, polar/non-polar sequence homology, Shannon entropy conservation, and other physicochemical properties of all specific 47 T-ORF8 protein variants, nine possible T-ORF8 unique variants were defined. The question as to whether T-ORF8 variants function similarly to the wild type ORF8 is yet to be investigated. A positive response to the question could exacerbate future COVID-19 waves, necessitating severe containment measures.

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