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Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2

The COVID-19 pandemic has created an urgent need for effective therapeutic and diagnostic strategies to manage the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of numerous variants of concern (VOCs) has made it challenging to develop targ...

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Autores principales: Longsompurana, Phoomintara, Rungrotmongkol, Thanyada, Plongthongkum, Nongluk, Wangkanont, Kittikhun, Wolschann, Peter, Poo-arporn, Rungtiva P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10597523/
https://www.ncbi.nlm.nih.gov/pubmed/37874836
http://dx.doi.org/10.1371/journal.pone.0293263
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author Longsompurana, Phoomintara
Rungrotmongkol, Thanyada
Plongthongkum, Nongluk
Wangkanont, Kittikhun
Wolschann, Peter
Poo-arporn, Rungtiva P.
author_facet Longsompurana, Phoomintara
Rungrotmongkol, Thanyada
Plongthongkum, Nongluk
Wangkanont, Kittikhun
Wolschann, Peter
Poo-arporn, Rungtiva P.
author_sort Longsompurana, Phoomintara
collection PubMed
description The COVID-19 pandemic has created an urgent need for effective therapeutic and diagnostic strategies to manage the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of numerous variants of concern (VOCs) has made it challenging to develop targeted therapies that are broadly specific in neutralizing the virus. In this study, we aimed to develop neutralizing nanobodies (Nbs) using computational techniques that can effectively neutralize the receptor-binding domain (RBD) of SARS-CoV-2 VOCs. We evaluated the performance of different protein-protein docking programs and identified HDOCK as the most suitable program for Nb/RBD docking with high accuracy. Using this approach, we designed 14 novel Nbs with high binding affinity to the VOC RBDs. The Nbs were engineered with mutated amino acids that interacted with key amino acids of the RBDs, resulting in higher binding affinity than human angiotensin-converting enzyme 2 (ACE2) and other viral RBDs or haemagglutinins (HAs). The successful development of these Nbs demonstrates the potential of molecular modeling as a low-cost and time-efficient method for engineering effective Nbs against SARS-CoV-2. The engineered Nbs have the potential to be employed in RBD-neutralizing assays, facilitating the identification of novel treatment, prevention, and diagnostic strategies against SARS-CoV-2.
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spelling pubmed-105975232023-10-25 Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2 Longsompurana, Phoomintara Rungrotmongkol, Thanyada Plongthongkum, Nongluk Wangkanont, Kittikhun Wolschann, Peter Poo-arporn, Rungtiva P. PLoS One Research Article The COVID-19 pandemic has created an urgent need for effective therapeutic and diagnostic strategies to manage the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of numerous variants of concern (VOCs) has made it challenging to develop targeted therapies that are broadly specific in neutralizing the virus. In this study, we aimed to develop neutralizing nanobodies (Nbs) using computational techniques that can effectively neutralize the receptor-binding domain (RBD) of SARS-CoV-2 VOCs. We evaluated the performance of different protein-protein docking programs and identified HDOCK as the most suitable program for Nb/RBD docking with high accuracy. Using this approach, we designed 14 novel Nbs with high binding affinity to the VOC RBDs. The Nbs were engineered with mutated amino acids that interacted with key amino acids of the RBDs, resulting in higher binding affinity than human angiotensin-converting enzyme 2 (ACE2) and other viral RBDs or haemagglutinins (HAs). The successful development of these Nbs demonstrates the potential of molecular modeling as a low-cost and time-efficient method for engineering effective Nbs against SARS-CoV-2. The engineered Nbs have the potential to be employed in RBD-neutralizing assays, facilitating the identification of novel treatment, prevention, and diagnostic strategies against SARS-CoV-2. Public Library of Science 2023-10-24 /pmc/articles/PMC10597523/ /pubmed/37874836 http://dx.doi.org/10.1371/journal.pone.0293263 Text en © 2023 Longsompurana et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Longsompurana, Phoomintara
Rungrotmongkol, Thanyada
Plongthongkum, Nongluk
Wangkanont, Kittikhun
Wolschann, Peter
Poo-arporn, Rungtiva P.
Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2
title Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2
title_full Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2
title_fullStr Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2
title_full_unstemmed Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2
title_short Computational design of novel nanobodies targeting the receptor binding domain of variants of concern of SARS-CoV-2
title_sort computational design of novel nanobodies targeting the receptor binding domain of variants of concern of sars-cov-2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10597523/
https://www.ncbi.nlm.nih.gov/pubmed/37874836
http://dx.doi.org/10.1371/journal.pone.0293263
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