Genomic Variations in ORF3a and ORF1ab Genes of SARS-nCoV2 Strain from Southern Pakistan

Emergence of COVID-19 pandemic has resulted in 8,578,283 total cases and 456,286 deaths worldwide as of June 19, 2020. We previously analysed genomic variants in two Northern Pakistani SARS-nCoV2 strains against USA and Chinese strains as reference, and hypothesized the putative role of observed variants in low severity of COVID-19 in Pakistan. Due to high variation rate in this virus, we further analysed the whole genome of Southern Pakistani SARS-nCoV2 MT500122 strain (Karachi-Pak) vs NC_045512 (Wuhan1-China) and observed 4 variants (3=SNPs,1=del). Three of variants at g.1604 (del ND447N), SNPs at g.1912 (p.=), g.10582 (p.=) and g.26022 (p.=) in ORF1ab and ORF3a genes respectively. ORF1ab encodes 16 non-structural polyproteins (nsps1-16) and plays role in viral replication. The codon change deletion in its sequence (as observed in MT500122) might have caused conformational alterations particularly in nsp2&5 structures which may obstruct its effectiveness. ORF3a is unique to SARS-nCoV2 and located in-between envelope and spike genes, which assist viral entry into the host cell by interacting with S gene. Alteration in its sequence might have hampered the activation of S gene and affect its binding capacity to host cell ACE2 and NRP1 receptors, which may greatly weaken its pathogenicity in its different strains and hence may vary severity of COVID-19. Nevertheless, intensive data and conclusive wet lab experiments are needed for validating this postulated hypothesis. Moreover, these variants have modifier to silent impact on further 9 genes e.g. M, N, S, E, ORFs 6, 7a, 7b, 8 and 10 as well. Advancements in understanding the role of these Pakistani SARS-nCoV2 genomic variations will be helpful in developing indigenous vaccines, diagnostic kits and drug development.