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.

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.