Mutational hotspots and conserved domains of SARS-CoV-2 genome in African population

Abstract

Background Since outbreak in December 2019, the highly infectious and pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over a million deaths globally. With increasing burden, the novel coronavirus has posed a dire threat to public health, social interaction, and global economy. Mutations in the SARS-CoV-2 genome are moderately evolving which might have contributed to its genome variability, transmission, replication efficiency, and virulence in different regions of the world. Results The present study elucidated the mutational landscape in the SARS-CoV-2 genome among the African populace, which may have contributed to the virulence, spread, and pathogenicity observed in the region. A total of 3045 SARS-CoV-2 complete protein sequences with the reference viral sequence (EPI_ISL_402124) were mined and analyzed. SARS-CoV-2 ORF1ab, spike, ORF3, ORF8, and nucleocapsid proteins were observed as mutational hotspots in the African population and may be of keen interest in understanding the viral host relationship, while there is conservation in the ORF6, ORF7a, ORF7b, ORF10, envelope, and membrane proteins. Conclusions The accumulation of moderate mutations (though slowly), in the SARS-CoV-2 genome as seen in this present study, could be a promising strategy to develop antiviral drugs or vaccines. These antiviral interventions should target viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.

RETRACTED ARTICLE: Genome sequence analysis of SARS-COV-2 isolated from a COVID-19 patient in Erbil, Iraq

“…Similarly, one study (Omotoso et al 2021 ) previously described a non-synonymous mutation at position 28854C > T (S194L), and in the current study such a mutation was observed in the N protein, which altered the original sequence of the open reading frame for the nucleocapsid (N) protein which is recognized to be important in virion assembly and structure (Weber et al 2021 ). Apart from frequent mutations, four variants were found in the spike glycoprotein (S); while triple mutations observed (L452R, E583D, D614G) were non-synonymous and were reported previously in strains from other countries (Harvey et al 2021 ) (Fig.…”

Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2

“…Previous studies have shown that remdesivir abrogates the canonical replicase activity of RdRp [ 50 , 51 ]. Notably, both palm and NiRAN domains amino acid sequences are highly conserved among various variants of concerns identified for SARS-CoV-2 [ 52 , 53 ]. We hypothesized that a combinatorial therapy of remdesivir and sorafenib may show synergistic effect to abolish the dual enzymatic activities of RdRp.…”

“…In addition, another study has shown the role of NiRAN domain in formation of a cap core structure [ 71 ]. In addition, the NiRAN domains of the RdRp molecules from the various variants of SARS-CoV-2, including the variants of concern, exhibit high degree of conservation, especially in the putative active site residues such as K73 and D218 [ 52 , 53 ]. Together our report and these recent studies hint at the indispensible nature of RdRp NiRAN domain for a successful viral replication in Nidoviruses, thus it is pertinent to explore in vivo anti-viral efficacies of compounds targeting the NiRAN catalytic functions.…”

SARS-CoV-2 originated from SARS-CoV-1-related Bat-CoVs through Pan-CoVs rather than from SARS-CoV-2-related Bat-CoVs

“…Furthermore coronaviruses in general, the quasispecies evolutionary processes have been well described (39,(42)(43)(44)(45)(46)(47)(48)(49). To support this, the ongoing SARS-CoV-2 outbreak in humans displayed widespread mutation/deletions and evolution in the critical genes of ORF1a (46,(50)(51)(52)(53)(54); spike gene (46,50,51,55,56); ORF3 (50,(57)(58)(59); and ORF8 (33,50,(60)(61)(62)(63)(64)(65) those viral proteins regulates the virus transmission, better adaptability to host and evasion of the host immunity. Furthermore, the presence of selection pressure for the evolution of the SARS-CoV-2 has been highly characterized (10,52,66,67).…”