Quercetin: A promising drug candidate against the potential SARS-CoV-2-Spike mutants with high viral infectivity
Computational and Structural Biotechnology Journal, doi:10.1016/j.csbj.2023.10.029
The emergence of SARS-CoV-2-Spike mutants not only enhances viral infectivity but also lead to treatment failure. Gaining a comprehensive understanding of the molecular binding mode between the mutant SARS-CoV-2-Spike and human ACE2 receptor is crucial for therapeutic development against this virus. Building upon our previous predictions and verifications regarding heightened viral infectivity of six potential SARS-CoV-2-Spike mutants, this study aims to further investigate the potential disruption of the interaction between these mutants and ACE2 by quercetin, a Chinese herbal compound. Molecular docking and dynamics simulations results reveal that the binding sites of quercetin particularly enriched around a specific "cavity" at the interface of Spike/ACE2 complex, indicating a favorable region for quercetin to interfere with Spike/ACE2 interaction. Virus infection assay confirms that quercetin not only attenuates wild-type virus infectivity but also suppresses the infectivity of all six tested SARS-CoV-2-Spike mutants. Therefore, quercetin represents a promising therapeutic candidate against both wild-type and potential future variants of SARS-CoV-2 exhibiting high viral infectivity.
Author contributions Liren Liu and Min Li designed and supervised the study and finalized the manuscript. Boyu Pan, Senbiao Fang, Liangjiao Wang and Zhanyu Pan contributed to the study design, performed the molecular docking & molecular dynamics simulations analyses and biological experiments and drafted the manuscript. All the authors approved the version to be published.
Author Statement We the undersigned declare that this manuscript entitled "Quercetin: A promising drug candidate against the potential SARS-CoV-2-Spike mutants with high viral infectivity" is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.
Conflict of Interest Statement All the authors (Boyu Pan, Senbiao Fang, Liangjiao Wang, Zhanyu Pan, Min Li and Liren Liu) declare that they have no competing interests.
Highlights: 1. Quercetin is mainly enriched in the cavity at the binding interface between Spike domain and the human ACE2 target.
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