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?:abstract
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The emerging novel coronavirus SARS-CoV-2 has created a global health crisis that warrants an accurate and detailed characterization of the rapidly evolving viral genome for understanding its epidemiology, pathogenesis and containment. Here, 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 real-timePCR 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, mostly (n =10) within the highly flexible linker region, were revealed and the rest within the NTD region. Furthermore, we predicted the possible consequence 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) co-occuring mutations (R203K and G204R) destabilized and decreased overall structural flexibility. The N protein of SARS-CoV-2 comprises an average of 1.2 mutations per strain compared to 4.4 and 0.4 in MERS-CoV and SARS-CoV, respectively. Despite being proposed as the alternate target to spike protein for vaccine and therapeutics, ongoing 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. This article is protected by copyright. All rights reserved.
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