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Mutational Analysis of SARS-CoV-2. ORF8 and the Evolution of the Delta and Omicron Variants
19 Pages Posted: 14 Mar 2022 Publication Status: Under Review
Abstract
SARS-CoV-2 is the virus responsible for the current pandemic. This virus is continually evolving; adapting to both innate and acquired immune responses and therapeutic drugs. Therefore, it is important to understand how the virus evolves to design the appropriate therapeutic and vaccine in preparation for future variants. Here, we used the online SARS-CoV-2 databases, Nextstrain and Ourworld, to map the evolution and epidemiology of the virus. We identified 30 high entropy residues which underwent a progressive evolution to arrive at the current dominant variant - Delta variant. The virus underwent mutational waves, with the first wave made up of structural proteins important in its infectivity and the second wave made up of the ORFs important for its contagion. The most important driver of the second wave is ORF8 mutations at residue 119 and 120. Further mutations of these two residues are creating new clades that are offshoots from the Delta backbone. More importantly the further expansion of the S protein in the Omicron variant is now followed with the acquisition of ORF8 mutations 119 and 120. These findings demonstrate how SARS-CoV-2 mutates and points to two evolutionary paths; 1) Mutational expansion on the Delta backbone among the ORFs and 2) Mutational expansion of the S protein on other backbones followed with mutational waves among the ORFs. Both are happening at the same time right now with the Omicron variant that is early in the first wave to follow with a more aggressive second wave of mutations.
Funding Information: Funding came from Oncotelic Inc.
Conflict of Interests: Authors are employee and/or contractor of Oncotelic Inc.
Keywords: SARS-CoV-2, ORF8 mutation, Delta variant, Omicron variant
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