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

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

Volume: 20 Issue: 5

Author(s): Timoteo Delgado-Maldonado, Luis Donaldo Gonzalez-Morales, Alfredo Juarez-Saldivar, Edgar E. Lara-Ramírez, Guadalupe Rojas-Verde, Adriana Moreno-Rodriguez, Debasish Bandyopadhyay and Gildardo Rivera*

Affiliation:

• Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710 Reynosa, México

Keywords: COVID-19, SARS-CoV-2, Spike protein, Ursolic acid, ACE2, virtual screening.

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)-ACE2 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.

Cite this article as:

Delgado-Maldonado Timoteo, Gonzalez-Morales Luis Donaldo, Juarez-Saldivar Alfredo, Lara-Ramírez Edgar E., Rojas-Verde Guadalupe, Moreno-Rodriguez Adriana, Bandyopadhyay Debasish and Rivera Gildardo*, Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2 Receptor Binding and their Biological Evaluation In vitro, Medicinal Chemistry 2024; 20 (5) . https://dx.doi.org/10.2174/0115734064279323231206091314