Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2-h Receptor Binding and their Biological Evaluation In vitro

Timoteo Delgado-Maldonado; Luis Donaldo Gonzalez-Morales; Alfredo Juarez-Saldivar; Edgar E Lara-Ramírez; Guadalupe Rojas-Verde; Adriana Rodriguez-Moreno; Debasish Bandyopadhyay; Gildardo Rivera

doi:10.2174/0115734064279323231206091314

Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2-h Receptor Binding and their Biological Evaluation In vitro

Med Chem. 2024 Jan 9. doi: 10.2174/0115734064279323231206091314. Online ahead of print.

Authors

Timoteo Delgado-Maldonado¹, Luis Donaldo Gonzalez-Morales¹, Alfredo Juarez-Saldivar¹, Edgar E Lara-Ramírez¹, Guadalupe Rojas-Verde², Adriana Rodriguez-Moreno³, Debasish Bandyopadhyay⁴, Gildardo Rivera¹

Affiliations

¹ Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710 Reynosa, México.
² Instituto de Biotecnología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Nuevo León CP. 66451, México.
³ Laboratorio de Estudios Epidemiológicos, Clínicos, Diseños Experimentales e Investigación, Facultad de Ciencias Químicas, Universidad Autónoma "Benito Juárez" de Oaxaca, Avenida Universidad S/N, Ex Hacienda Cinco Señores, Oaxaca 68120, México.
⁴ Department of Chemistry and SEEMS, University of Texas Rio Grande Valley, Edinburg, Texas 78539, United States of America.

PMID: 38204279
DOI: 10.2174/0115734064279323231206091314

Abstract

Background: In the last years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 760 million infections and 6.9 million deaths. Currently, remains a public health problem with limited pharmacological treatments. Among the virus drug targets, the SARS-CoV-2 spike protein attracts the development of new anti-SARS-CoV-2 agents.

Objective: The aim of this work was to identify new compounds derived from natural products (BIOFACQUIM and Selleckchem databases) as potential inhibitors of the spike receptor binding domain (RBD)-ACE2h binding complex.

Methods: Molecular docking, molecular dynamics simulations, and ADME-Tox analysis were performed to screen and select the potential inhibitors. ELISA-based enzyme assay was done to confirm our predictive model.

Results: Twenty compounds were identified as potential binders of RBD of the spike protein. In vitro assay showed compound B-8 caused 48% inhibition at 50 μM, and their binding pattern exhibited interactions via hydrogen bonds with the key amino acid residues present on the RBD.

Conclusion: Compound B-8 can be used as a scaffold to develop new and more efficient antiviral drugs.

Keywords: COVID-19; SARS-CoV-2; Spike protein; Ursolic acid; inhibitors.