Preprint Short Note Version 1 This version is not peer-reviewed

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

Version 1 : Received: 20 June 2020 / Approved: 21 June 2020 / Online: 21 June 2020 (10:04:09 CEST)

How to cite: Saif, R.; Ejaz, A.; Mahmood, T.; Zia, S.; Qureshi, A.R. Genomic Variations in ORF3a and ORF1ab Genes of SARS-nCoV2 Strain from Southern Pakistan. Preprints 2020, 2020060247 (doi: 10.20944/preprints202006.0247.v1). Saif, R.; Ejaz, A.; Mahmood, T.; Zia, S.; Qureshi, A.R. Genomic Variations in ORF3a and ORF1ab Genes of SARS-nCoV2 Strain from Southern Pakistan. Preprints 2020, 2020060247 (doi: 10.20944/preprints202006.0247.v1).

Abstract

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) from NCBI 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 play role in viral replication. The codon change deletion in its sequence (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 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 targets.

Subject Areas

Southern Pakistani SARS-nCoV2; ORF1ab variations; ORF3a variations; whole genome analysis

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.