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

  • Hassan, Sk Sarif1
  • Kodakandla, Vaishnavi2
  • Redwan, Elrashdy M3
  • Lundstrom, Kenneth4
  • Pal Choudhury, Pabitra5
  • Abd El-Aziz, Tarek Mohamed6
  • Takayama, Kazuo7
  • Kandimalla, Ramesh8
  • Lal, Amos9
  • Serrano-Aroca, Ángel10
  • Azad, Gajendra Kumar11
  • Aljabali, Alaa A A12
  • Palù, Giorgio13
  • Chauhan, Gaurav14
  • Adadi, Parise15
  • Tambuwala, Murtaza16
  • Brufsky, Adam M17
  • Baetas-da-Cruz, Wagner18
  • Barh, Debmalya19
  • Azevedo, Vasco20
  • And 4 more
  • 1 Department of Mathematics, Pingla Thana Mahavidyalaya, Maligram, India. , (India)
  • 2 Department of Life sciences, Sophia College For Women, University of Mumbai, Mumbai, India. , (India)
  • 3 Faculty of Science, Department of Biological Science, King Abdulaziz University, Jeddah, Saudi Arabia. , (Saudi Arabia)
  • 4 PanTherapeutics, Lutry, Switzerland. , (Switzerland)
  • 5 Applied Statistics Unit, Indian Statistical Institute, Kolkata, India. , (India)
  • 6 Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States. , (United States)
  • 7 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. , (Japan)
  • 8 Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India. , (India)
  • 9 Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, NY, United States. , (United States)
  • 10 Biomaterials and Bioengineering Lab, Centro de Investigacion Traslacional San Alberto Magno, Universidad Catolica de Valencia San Vicente Martir, Valencia, Spain. , (Spain)
  • 11 Department of Zoology, Patna University, Patna, India. , (India)
  • 12 Department of Pharmaceutics and Pharmaceutical, Yarmouk University, Irbid, Jordan. , (Jordan)
  • 13 Department of Molecular Medicine, University of Padova, Padova, Italy. , (Italy)
  • 14 School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey, Mexico. , (Mexico)
  • 15 Department of Food Science, University of Otago, University of Otago, Dunedin, New Zealand. , (New Zealand)
  • 16 School of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine, UK.
  • 17 Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. , (United States)
  • 18 Translational Laboratory in Molecular Physiology, Centre for Experimental Surgery, College of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. , (Brazil)
  • 19 Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and 46 Applied Biotechnology (IIOAB), Nonakuri, India. , (India)
  • 20 Departamento de Genetica, Ecologia e Evolucao, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. , (Brazil)
  • 21 Neuroscience Center of Excellence, School of Medicine, LSU Health New Orleans, New Orleans, LA, United States. , (United States)
  • 22 Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia, Jequié, Brazil. , (Brazil)
  • 23 Departamento de Ciencias Biologicas (DCB), Programa de Pos-Graduacao em Genetica e Biologia Molecular (PPGGBM), Universidade Estadual de Santa Cruz (UESC), Ilheus, Brazil. , (Brazil)
  • 24 Department of Molecular Medicine, University of South Florida, Tampa, FL, United States. , (United States)
Published Article
Publication Date
Jan 01, 2022
DOI: 10.7717/peerj.13136
PMID: 35341060


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. © 2022 Hassan et al.

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