Dataset Information

Comparing the Nucleocapsid Proteins of Human Coronaviruses: Structure, Immunoregulation, Vaccine, and Targeted Drug.

ABSTRACT: The seven pathogenic human coronaviruses (HCoVs) include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, which usually cause mild upper respiratory tract diseases, and SARS-CoV, MERS-CoV, and SARS-CoV-2, which cause a severe acute respiratory syndrome. The nucleocapsid (N) protein, as the dominant structural protein from coronaviruses that bind to the genomic RNA, participates in various vital activities after virus invasion and will probably become a promising target of antiviral drug design. Therefore, a comprehensive literature review of human coronavirus' pathogenic mechanism and therapeutic strategies is necessary for the control of the pandemic. Here, we give a systematic summary of the structures, immunoregulation, and potential vaccines and targeted drugs of the HCoVs N protein. First, we provide a general introduction to the fundamental structures and molecular function of N protein. Next, we outline the N protein mediated immune regulation and pathogenesis mechanism. Finally, we comprehensively summarize the development of potential N protein-targeted drugs and candidate vaccines to treat coronavirus disease 2019 (COVID-19). We believe this review provides insight into the virulence and transmission of SARS-CoV-2 as well as support for further study on epidemic control of COVID-19.

SUBMITTER: Zhang B

PROVIDER: S-EPMC9099148 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Comparing the Nucleocapsid Proteins of Human Coronaviruses: Structure, Immunoregulation, Vaccine, and Targeted Drug.

Zhang Bo B Tian Junjie J Zhang Qintao Q Xie Yan Y Wang Kejia K Qiu Shuyi S Lu Keyu K Liu Yang Y

Frontiers in molecular biosciences 20220429

The seven pathogenic human coronaviruses (HCoVs) include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, which usually cause mild upper respiratory tract diseases, and SARS-CoV, MERS-CoV, and SARS-CoV-2, which cause a severe acute respiratory syndrome. The nucleocapsid (N) protein, as the dominant structural protein from coronaviruses that bind to the genomic RNA, participates in various vital activities after virus invasion and will probably become a promising target of antiviral drug design. T ...[more]

PMID: 35573742

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Project description:Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. The spike (S) homotrimers bind to their receptors via the receptor-binding domain (RBD), which is a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs exist two different conformational states (lying or standing) in the prefusion S-trimer structure. Then, the differences in the immune responses to RBDs from these coronaviruses were analyzed structurally and immunologically. Our results showed that more RBD-specific antibodies (antibody titers: 1.28×105; 2.75×105) were induced by the S-trimer with the RBD in the "standing" state (SARS-CoV and SARS-CoV-2) than the S-trimer with the RBD in the "lying" state (HCoV-229E, antibody titers: <500), and more S-trimer-specific antibodies were induced by the RBD in the SARS-CoV and SARS-CoV-2 (antibody titers: 6.72×105; 5×105) than HCoV-229E (antibody titers:1.125×103). Besides, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was lower than S-trimer, and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus Our findings will provide important implications for future development of coronavirus vaccines.Importance Outbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in "lying" and "standing" states in the prefusion S-trimer structure. Here, we evaluated the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that the S-trimer and RBD are both candidates for subunit vaccines in Beta-coronavirus (SARS-CoV and SARS-CoV-2) with a RBD "standing" state. However, for Alpha-coronavirus (HCoV-229E) with a RBD "lying" state, the S-trimer may be more suitable for subunit vaccines than the RBD. Our results will provide novel ideas for the development of vaccines targeting S protein in the future.

Dataset Information

Comparing the Nucleocapsid Proteins of Human Coronaviruses: Structure, Immunoregulation, Vaccine, and Targeted Drug.

Publications

Comparing the Nucleocapsid Proteins of Human Coronaviruses: Structure, Immunoregulation, Vaccine, and Targeted Drug.

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