Variability of Accessory Proteins Rules the SARS-CoV-2 Pathogenicity

Sk. Sarif Hassan; Pabitra Pal Choudhury; Vladimir Nikolaevich Uversky; Guy W. Dayhoff; Alaa A. A. Aljabali; Bruce D. Uhal; Kenneth H. Lundstrom; Nima Rezaei; Murat Seyran; Damiano Pizzol; Parise Adadi; Amos Lal; António Soares; Tarek Mohamed Abd El‐Aziz; Ramesh J. L. Kandimalla; Murtaza M. Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas‐da‐Cruz; Kazuo Takayama; Ángel Serrano‐Aroca; Gaurav Chauhan; Giorgio Palù; Adam Brufsky

doi:10.1101/2020.11.06.372227

BioinformaticsbioRxivNov 6, 2020

Preprint

Variability of Accessory Proteins Rules the SARS-CoV-2 Pathogenicity

Sk. Sarif Hassan iD, Pabitra Pal Choudhury iD, Vladimir Nikolaevich Uversky iD, Guy W. Dayhoff iD, Alaa A. A. Aljabali iD, Bruce D. Uhal iD, Kenneth H. Lundstrom iD, Nima Rezaei iD, Murat Seyran, Damiano Pizzol iD, Parise Adadi iD, Amos Lal iD, António Soares iD, Tarek Mohamed Abd El‐Aziz iD, Ramesh J. L. Kandimalla iD, Murtaza M. Tambuwala iD, Gajendra Kumar Azad iD, Samendra P. Sherchan iD, Wagner Baetas‐da‐Cruz iD, Kazuo Takayama iD, Ángel Serrano‐Aroca iD, Gaurav Chauhan iD, Giorgio Palù iD, Adam Brufsky iD

Abstract

The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) which is pandemic with an estimated fatality rate less than 1% is ongoing. SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 with putative functions to manipulate host immune mechanisms such as interferons, immune signaling receptor NLRP3 (NOD-, LRR-, and pyrin domain-containing 3) inflammasome, inflammatory cytokines such as interleukin 1{beta} (IL-1{beta}) are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins of all complete proteomes (available as of October 26, 2020, in the National Center for Biotechnology Information depository) of SARS-CoV-2, were observed across six continents. Across all continents, the decreasing order of percentage of unique variations in the accessory proteins was found to be ORF3a>ORF8>ORF7a>ORF6>ORF10>ORF7b. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. This finding suggests that the wide variations of accessory proteins seem to govern the pathogenicity of SARS-CoV-2, and consequently, certain propositions and recommendations can be made in the public interest.

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