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 AzevedoNikolas G. Bazan, Bruno Silva Andrade, Raner José Santana Silva, Vladimir N. Uversky

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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.
Original languageEnglish
Article numbere13136
Pages (from-to)1-28
Number of pages28
Publication statusPublished (in print/issue) - 21 Mar 2022

Bibliographical note

Publisher Copyright:
© 2022 Hassan et al.


  • ORF8
  • SARS-CoV-2
  • COVID-19
  • Truncated
  • Intrinsically disordered region
  • Truncation mutation
  • Continent distribution


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