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

Autor: Longsompurana P; Biological Engineering Program, Faculty of Engineering, King Mongkut's University of Technology Thonburi, Bangkok, Thailand., Rungrotmongkol T; Center of Excellence in Biocatalyst and Sustainable Biotechnology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, Thailand., Plongthongkum N; Biological Engineering Program, Faculty of Engineering, King Mongkut's University of Technology Thonburi, Bangkok, Thailand., Wangkanont K; Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.; Center of Excellence for Molecular Crop, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand., Wolschann P; Institute of Theoretical Chemistry, University of Vienna, Vienna, Austria., Poo-Arporn RP; Biological Engineering Program, Faculty of Engineering, King Mongkut's University of Technology Thonburi, Bangkok, Thailand.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Oct 24; Vol. 18 (10), pp. e0293263. Date of Electronic Publication: 2023 Oct 24 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0293263
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Longsompurana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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