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Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies.
Viruses. 2021 Jan 19; 13(1)V

Abstract

Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike's receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.

Links

Authors+Show Affiliations

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.

Parker Miller E

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.

MeSH

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCOVID-19Epitope MappingEpitopesHumansImmunization, PassiveMiddle East Respiratory Syndrome CoronavirusSevere acute respiratory syndrome-related coronavirusSARS-CoV-2Severe Acute Respiratory SyndromeSpike Glycoprotein, CoronavirusViral VaccinesVirus InternalizationCOVID-19 Serotherapy

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Review

Language

eng

PubMed ID

33477902

Citation

Finkelstein, Maxwell T., et al. "Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies." Viruses, vol. 13, no. 1, 2021.

Finkelstein MT, Mermelstein AG, Parker Miller E, et al. Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies. Viruses. 2021;13(1).

Finkelstein, M. T., Mermelstein, A. G., Parker Miller, E., Seth, P. C., Stancofski, E. D., & Fera, D. (2021). Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies. Viruses, 13(1). https://doi.org/10.3390/v13010134

Finkelstein MT, et al. Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies. Viruses. 2021 Jan 19;13(1) PubMed PMID: 33477902.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies. AU - Finkelstein,Maxwell T, AU - Mermelstein,Adam G, AU - Parker Miller,Emma, AU - Seth,Paul C, AU - Stancofski,Erik-Stephane D, AU - Fera,Daniela, Y1 - 2021/01/19/ PY - 2020/12/18/received PY - 2021/1/1/revised PY - 2021/1/14/accepted PY - 2021/1/22/entrez PY - 2021/1/23/pubmed PY - 2021/2/3/medline KW - COVID-19 KW - SARS-CoV-2 KW - coronavirus KW - immunogen KW - neutralizing antibodies KW - spike JF - Viruses JO - Viruses VL - 13 IS - 1 N2 - Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike's receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection. SN - 1999-4915 UR - https://www.unboundmedicine.com/medline/citation/33477902/Structural_Analysis_of_Neutralizing_Epitopes_of_the_SARS_CoV_2_Spike_to_Guide_Therapy_and_Vaccine_Design_Strategies_ DB - PRIME DP - Unbound Medicine ER -