An Issue of Concern: Unique Truncated ORF8 Protein Variants of SARS-CoV-2

Hassan, S. S.; Kodakandla, V.; Redwan, E. M.; Lundstrom, K.; Pal Choudhury, P.; Abd El-Aziz, T. M.; Takayama, K.; Kandimalla, R.; Lal, A.; Serrano-Aroca, A.; Azad, G. K.; Aljabali, A. A. A.; Palu, G.; Chauhan, G.; Adadi, P.; Tambuwala, M.; Brufsky, A.; Baetas-da-Cruz, W.; Barh, D.; Bazan, N. G.; Uversky, V. N.

doi:10.1101/2021.05.25.445557

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bioRxiv · 10.1101/2021.05.25.445557

An Issue of Concern: Unique Truncated ORF8 Protein Variants of SARS-CoV-2

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Abstract

Open reading frame 8 (ORF8) protein is one of the most evolving 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 presentation of viral antigens by the major histocompatibility complex class I (MHC-I) and interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 to evade immunity and replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein defines the B.1.1.7 lineage of SARS-CoV-2, which is engendering the second wave of COVID-19. In the present study, 47 unique truncated ORF8 proteins (T-ORF8) due to the Q27STOP mutations were identified among 49055 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 includes 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, a collection of nine possible T-ORF8 unique variants were defined. The question of whether T-ORF8 variants work similarly to ORF8 has yet to be investigated. A positive response to the question could exacerbate future COVID-19 waves, necessitating severe containment measures.

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Hassan, S. S., Kodakandla, V., Redwan, E. M., Lundstrom, K., Pal Choudhury, P., Abd El-Aziz, T. M., Takayama, K., Kandimalla, R., Lal, A., Serrano-Aroca, A., Azad, G. K., Aljabali, A. A. A., Palu, G., Chauhan, G., Adadi, P., Tambuwala, M., Brufsky, A., Baetas-da-Cruz, W., Barh, D., Bazan, N. G., Uversky, V. N.. 2021-05-25. An Issue of Concern: Unique Truncated ORF8 Protein Variants of SARS-CoV-2. https://doi.org/10.1101/2021.05.25.445557

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