Urtica dioica agglutinin (UDA) as a potential candidate for inhibition of SARS-CoV-2 Omicron variants: In silico prediction and experimental validation.

Autor: Sabzian-Molaei F; Laboratory of Regenerative Medicine & Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran., Hosseini S; Zahedan University of Medical Sciences, Zahedan, Iran., Alipour A; Department of Nanobiotechnology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: a_alipour@pasteur.ac.ir., Ghaderi H; Laboratory of Regenerative Medicine & Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran., Fotouhi-Chahouki F; Department of influenza and other respiratory viruses, Pasteur Institute of Iran, Tehran, Iran., Hadi A; Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran. Electronic address: s.amin.hadi@gmail.com., Shahsavarani H; Laboratory of Regenerative Medicine & Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran; Department of Cell and Molecular Biology, Faculty of Life science and Biotechnology, Shahid Beheshti University, Tehran, Iran. Electronic address: hosein.shahsavarani@gmail.com.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2023 Mar; Vol. 111, pp. 154648. Date of Electronic Publication: 2023 Jan 06.
DOI: 10.1016/j.phymed.2023.154648
Abstrakt: Background: The high number of mutations and consequent structure modifications in a Receptor-Binding Domain (RBD) of the spike protein of the Omicron variant of SARS-CoV-2 increased concerns about evading neutralization by antibodies induced by previous infection or vaccination. Thus, developing novel drugs with potent inhibitory activity can be considered an alternative for treating this highly transmissible variant. Considering that Urtica dioica agglutinin (UDA) displays antiviral activity against SARS-CoV-2, the potency of this lectin to inhibit the Receptor Binding Domain of the Omicron variant (RBD Omic ) was examined in this study.
Purpose: This study examines how UDA inhibits the Omicron variant of SARS-CoV-2 by blocking its RBD, using a combination of in silico and experimental methods.
Methods: To investigate the interaction between UDA and RBD Omic , the CLUSPRO 2.0 web server was used to dock the RBD Omic -UDA complex, and molecular dynamics simulations were performed by the Gromacs 2020.2 software to confirm the stability of the selected docked complex. Finally, the binding affinity (ΔG) of the simulation was calculated using MM-PBSA. In addition, ELISA and Western blot tests were used to examine UDA's binding to RBD Omic .
Results: Based on the docking results, UDA forms five hydrogen bonds with the RBD Omic active site, which contains mutated residues Tyr501, Arg498, Arg493, and His505. According to MD simulations, the UDA-RBD Omic complex is stable over 100 ns, and its average binding energy during the simulation is -87.201 kJ/mol. Also, the ELISA test showed that UDA significantly binds to RBD Omic , and by increasing the concentration of UDA protein, the attachment to RBD Omic became stronger. In Western blotting, RBD Omic was able to attach to and detect UDA.
Conclusion: This study indicates that UDA interaction with RBD Omic prevents virus attachment to Angiotensin-converting enzyme 2 (ACE2) and, therefore, its entry into the host cell. Altogether, UDA exhibited a significant suppression effect on the Omicron variant and can be considered a new candidate to improve protection against severe infection of this variant.
Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.
(Copyright © 2023 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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