Tags

Type your tag names separated by a space and hit enter

Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein and its consequences.
J Med Virol. 2021 04; 93(4):2177-2195.JM

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.

Authors+Show Affiliations

Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh.Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.Department of Microbiology, University of Dhaka, Dhaka, Bangladesh. Department of Gynecology, Obstetrics and Reproductive Health, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.Department of Microbiology, University of Dhaka, Dhaka, Bangladesh. Department of Microbiology, Jahangirnagar University, Savar, Dhaka, Bangladesh.Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33095454

Citation

Rahman, M Shaminur, et al. "Evolutionary Dynamics of SARS-CoV-2 Nucleocapsid Protein and Its Consequences." Journal of Medical Virology, vol. 93, no. 4, 2021, pp. 2177-2195.
Rahman MS, Islam MR, Alam ASMRU, et al. Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein and its consequences. J Med Virol. 2021;93(4):2177-2195.
Rahman, M. S., Islam, M. R., Alam, A. S. M. R. U., Islam, I., Hoque, M. N., Akter, S., Rahaman, M. M., Sultana, M., & Hossain, M. A. (2021). Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein and its consequences. Journal of Medical Virology, 93(4), 2177-2195. https://doi.org/10.1002/jmv.26626
Rahman MS, et al. Evolutionary Dynamics of SARS-CoV-2 Nucleocapsid Protein and Its Consequences. J Med Virol. 2021;93(4):2177-2195. PubMed PMID: 33095454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein and its consequences. AU - Rahman,M Shaminur, AU - Islam,M Rafiul, AU - Alam,A S M Rubayet Ul, AU - Islam,Israt, AU - Hoque,M Nazmul, AU - Akter,Salma, AU - Rahaman,Md Mizanur, AU - Sultana,Munawar, AU - Hossain,M Anwar, Y1 - 2020/11/10/ PY - 2020/09/01/received PY - 2020/10/17/revised PY - 2020/10/20/accepted PY - 2020/10/24/pubmed PY - 2021/3/20/medline PY - 2020/10/23/entrez KW - CDC KW - COVID-19 KW - N protein KW - SARS-CoV-2 KW - deletions KW - mutations KW - primer KW - stability SP - 2177 EP - 2195 JF - Journal of medical virology JO - J Med Virol VL - 93 IS - 4 N2 - 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. SN - 1096-9071 UR - https://www.unboundmedicine.com/medline/citation/33095454/Evolutionary_dynamics_of_SARS_CoV_2_nucleocapsid_protein_and_its_consequences_ L2 - https://doi.org/10.1002/jmv.26626 DB - PRIME DP - Unbound Medicine ER -