Evolutionary dynamics of SARS‐CoV‐2 nucleocapsid protein and its consequences
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Abstract
The emerged novel coronavirus severe acute respiratory syndrome coronavirus 2 (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‐time polymerase chain reaction 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 the 3′‐end mismatch to the primer‐pair of 11 well‐characterized primer sets. Noteworthily, CDC (USA) recommended the N2 primer set contained a lower mismatch than the other primer sets. Moreover, 684 amino acid (aa) substitutions were located across 317 (75.66% of total aa) unique positions including 82, 21, and 83 of those in the RNA binding N‐terminal domain (NTD), SR‐rich region, and C‐terminal dimerization domain, respectively. Moreover, 11 in‐frame deletions, mostly ( n = 10) within the highly flexible linker region, were revealed, and the rest was 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 a 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 Middle East respiratory syndrome‐related coronavirus and SARS‐CoV, respectively. Despite being proposed as the alternative target to spike protein for vaccine and therapeutics, the ongoing evolution of the N protein may challenge these endeavors, thus needing 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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SciScore for 10.1101/2020.08.05.237339: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources The 3D structure was validated using the Ramachandran plot (>90 restudies were allowed region) in PROCHECK v3.5 server (https://servicesn.mbi.ucla.edu/PROCHECK/ PROCHECKsuggested: (PROCHECK, RRID:SCR_019043)Finally, the energy minimized and validated 3D structure was visualized by PyMol v2.4 (DeLano, 2002). PyMolsuggested: (PyMOL, RRID:SCR_000305)For two or more mutational effect prediction, we used FoldX v. FoldXsuggested: (FoldX, RRID:SCR_008522)5.0 with their default parameters and three times run (Delgado et al., 2019) plugin in YASARA. YASARAsuggested: (YASARA, RRID:SCR_017591)Results …
SciScore for 10.1101/2020.08.05.237339: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources The 3D structure was validated using the Ramachandran plot (>90 restudies were allowed region) in PROCHECK v3.5 server (https://servicesn.mbi.ucla.edu/PROCHECK/ PROCHECKsuggested: (PROCHECK, RRID:SCR_019043)Finally, the energy minimized and validated 3D structure was visualized by PyMol v2.4 (DeLano, 2002). PyMolsuggested: (PyMOL, RRID:SCR_000305)For two or more mutational effect prediction, we used FoldX v. FoldXsuggested: (FoldX, RRID:SCR_008522)5.0 with their default parameters and three times run (Delgado et al., 2019) plugin in YASARA. YASARAsuggested: (YASARA, RRID:SCR_017591)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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