Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin

Zhou, Zhijian; Qiu, Ye; Ge, Xing‐Yi

doi:10.1101/2020.06.04.135293

Cited by 2 publications

References 43 publications

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A comprehensive overview of identified mutations in SARS CoV-2 spike glycoprotein among Iranian patients

Eslami

Glassy

Ghafouri‐Fard

2022

Gene

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Since late 2019, when SARS-CoV-2 was reported at Wuhan, several sequence analyses have been performed and SARS-CoV-2 genome sequences have been submitted in various databases. Moreover, the impact of these variants on infectivity and response to neutralizing antibodies has been assessed. In the present study, we retrieved a total number of 176 complete and high-quality S glycoprotein sequences of Iranian SARS-COV-2 in public database of the GISAID and GenBank from April 2020 up to May 2021. Then, we identified the number of variables, singleton and parsimony informative sites at both gene and protein levels and discussed the possible functional consequences of important mutations on the infectivity and response to neutralizing antibodies. Phylogenetic tree was constructed to represent the relationship between Iranian SARS-COV2 and variants of concern (VOC), variants of interest (VOI) and reference sequence. We found that the four current VOCs – Alpha, Beta, Gamma and Delta - are circulated in different regions in Iran. The Delta variant is notably more transmissible than other variants, and is expected to become a dominant variant. However, some of the Delta variants in Iran carry an additional mutation, namely E1202Q in the HR2 subdomain that might confer an advantage to viral/cell membrane fusion process. We also observed some more common mutations such as an N-terminal domain (NTD) deletion at position I210 and P863H in fusion peptide-heptad repeat 1 span region in Iranian SARS-COV-2. The reported mutations in the current project have practical significance in prediction of disease spread as well as design of vaccines and drugs.

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A comprehensive overview of identified mutations in SARS CoV-2 spike glycoprotein among Iranian patients

Eslami

Glassy

Ghafouri‐Fard

2022

Gene

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Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein (N protein) and its consequences

Asmr

et al. 2020

Preprint

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The emerging novel coronavirus SARS-CoV-2 has created a global confusing pandemic health crisis that warrants an accurate and detailed characterization of the rapidly evolving viral genome for understanding its epidemiology, pathogenesis and containment. We explored 61,485 sequences of the Nucleocapsid (N) protein, a potent diagnostic and prophylactic target, for identifying the mutations to review their roles in RT-PCR based diagnosis and observe consequent impacts. Compared to the Wuhan reference strain, a total of 1034 unique nucleotide mutations were identified in the mutant strains (49.15%, n=30,221) globally. Of these mutations, 367 occupy primer binding sites including 3’-end mismatch to primer-pair of 11 well characterized primer sets. Noteworthy, CDC (USA) recommended N2 primer set contained lower mismatch than the other primer sets. Moreover, 684 amino acid (aa) substitutions located across 317 (75.66% of total aa) unique positions including 82, 21, and 83 of those in RNA binding N-terminal domain (NTD), SR-rich region, and C-terminal dimerization domain (CTD), respectively. Moreover, 11 in-frame deletions were revealed, mostly (n =10) within the highly flexible linker region, and the rest within the NTD region. Furthermore, we predicted the possible consequences of high-frequency mutations (≥ 20) and deletions on the tertiary structure of the N protein. Remarkably, we observed that high frequency (67.94% of mutated sequences) coevolving mutations (R203K and G204R) destabilized and decreased overall structural flexibility. Despite being proposed as the alternate target to spike protein for vaccine and therapeutics, ongoing nonsynonymous evolution of the N protein may challenge the endeavors, thus need further immunoinformatics analyses. Therefore, continuous monitoring is required for tracing the ongoing evolution of the SARS-CoV-2 N protein in prophylactic and diagnostic interventions.

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Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin

Cited by 2 publications

References 43 publications

A comprehensive overview of identified mutations in SARS CoV-2 spike glycoprotein among Iranian patients

A comprehensive overview of identified mutations in SARS CoV-2 spike glycoprotein among Iranian patients

Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein (N protein) and its consequences

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