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Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates infection by attachment of the surface-exposed spike glycoprotein to the host cell receptors. The spike glycoprotein (S) is a promising target for inducing immune responses and providing protection; thus the ongoing efforts for t...

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Autores principales: Vishwakarma, Preeti, Yadav, Naveen, Rizvi, Zaigham Abbas, Khan, Naseem Ahmed, Chiranjivi, Adarsh Kumar, Mani, Shailendra, Bansal, Manish, Dwivedi, Prabhanjan, Shrivastava, Tripti, Kumar, Rajesh, Awasthi, Amit, Ahmed, Shubbir, Samal, Sweety
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032902/
https://www.ncbi.nlm.nih.gov/pubmed/33841395
http://dx.doi.org/10.3389/fimmu.2021.613045
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author Vishwakarma, Preeti
Yadav, Naveen
Rizvi, Zaigham Abbas
Khan, Naseem Ahmed
Chiranjivi, Adarsh Kumar
Mani, Shailendra
Bansal, Manish
Dwivedi, Prabhanjan
Shrivastava, Tripti
Kumar, Rajesh
Awasthi, Amit
Ahmed, Shubbir
Samal, Sweety
author_facet Vishwakarma, Preeti
Yadav, Naveen
Rizvi, Zaigham Abbas
Khan, Naseem Ahmed
Chiranjivi, Adarsh Kumar
Mani, Shailendra
Bansal, Manish
Dwivedi, Prabhanjan
Shrivastava, Tripti
Kumar, Rajesh
Awasthi, Amit
Ahmed, Shubbir
Samal, Sweety
author_sort Vishwakarma, Preeti
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates infection by attachment of the surface-exposed spike glycoprotein to the host cell receptors. The spike glycoprotein (S) is a promising target for inducing immune responses and providing protection; thus the ongoing efforts for the SARS-CoV-2 vaccine and therapeutic developments are mostly spiraling around S glycoprotein. The matured functional spike glycoprotein is presented on the virion surface as trimers, which contain two subunits, such as S1 (virus attachment) and S2 (virus fusion). The S1 subunit harbors the N-terminal domain (NTD) and the receptor-binding domain (RBD). The RBD is responsible for binding to host-cellular receptor angiotensin-converting enzyme 2 (ACE2). The NTD and RBD of S1, and the S2 of S glycoprotein are the major structural moieties to design and develop spike-based vaccine candidates and therapeutics. Here, we have identified three novel epitopes (20-amino acid peptides) in the regions NTD, RBD, and S2 domains, respectively, by structural and immunoinformatic analysis. We have shown as a proof of principle in the murine model, the potential role of these novel epitopes in-inducing humoral and cellular immune responses. Further analysis has shown that RBD and S2 directed epitopes were able to efficiently inhibit the replication of SARS-CoV-2 wild-type virus in vitro suggesting their role as virus entry inhibitors. Structural analysis revealed that S2-epitope is a part of the heptad repeat 2 (HR2) domain which might have plausible inhibitory effects on virus fusion. Taken together, this study discovered novel epitopes that might have important implications in the development of potential SARS-CoV-2 spike-based vaccine and therapeutics.
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spelling pubmed-80329022021-04-10 Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro Vishwakarma, Preeti Yadav, Naveen Rizvi, Zaigham Abbas Khan, Naseem Ahmed Chiranjivi, Adarsh Kumar Mani, Shailendra Bansal, Manish Dwivedi, Prabhanjan Shrivastava, Tripti Kumar, Rajesh Awasthi, Amit Ahmed, Shubbir Samal, Sweety Front Immunol Immunology Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates infection by attachment of the surface-exposed spike glycoprotein to the host cell receptors. The spike glycoprotein (S) is a promising target for inducing immune responses and providing protection; thus the ongoing efforts for the SARS-CoV-2 vaccine and therapeutic developments are mostly spiraling around S glycoprotein. The matured functional spike glycoprotein is presented on the virion surface as trimers, which contain two subunits, such as S1 (virus attachment) and S2 (virus fusion). The S1 subunit harbors the N-terminal domain (NTD) and the receptor-binding domain (RBD). The RBD is responsible for binding to host-cellular receptor angiotensin-converting enzyme 2 (ACE2). The NTD and RBD of S1, and the S2 of S glycoprotein are the major structural moieties to design and develop spike-based vaccine candidates and therapeutics. Here, we have identified three novel epitopes (20-amino acid peptides) in the regions NTD, RBD, and S2 domains, respectively, by structural and immunoinformatic analysis. We have shown as a proof of principle in the murine model, the potential role of these novel epitopes in-inducing humoral and cellular immune responses. Further analysis has shown that RBD and S2 directed epitopes were able to efficiently inhibit the replication of SARS-CoV-2 wild-type virus in vitro suggesting their role as virus entry inhibitors. Structural analysis revealed that S2-epitope is a part of the heptad repeat 2 (HR2) domain which might have plausible inhibitory effects on virus fusion. Taken together, this study discovered novel epitopes that might have important implications in the development of potential SARS-CoV-2 spike-based vaccine and therapeutics. Frontiers Media S.A. 2021-03-26 /pmc/articles/PMC8032902/ /pubmed/33841395 http://dx.doi.org/10.3389/fimmu.2021.613045 Text en Copyright © 2021 Vishwakarma, Yadav, Rizvi, Khan, Chiranjivi, Mani, Bansal, Dwivedi, Shrivastava, Kumar, Awasthi, Ahmed and Samal. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Vishwakarma, Preeti
Yadav, Naveen
Rizvi, Zaigham Abbas
Khan, Naseem Ahmed
Chiranjivi, Adarsh Kumar
Mani, Shailendra
Bansal, Manish
Dwivedi, Prabhanjan
Shrivastava, Tripti
Kumar, Rajesh
Awasthi, Amit
Ahmed, Shubbir
Samal, Sweety
Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro
title Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro
title_full Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro
title_fullStr Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro
title_full_unstemmed Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro
title_short Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro
title_sort severe acute respiratory syndrome coronavirus 2 spike protein based novel epitopes induce potent immune responses in vivo and inhibit viral replication in vitro
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032902/
https://www.ncbi.nlm.nih.gov/pubmed/33841395
http://dx.doi.org/10.3389/fimmu.2021.613045
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