Stilbenoids Prevent the Entry of SARS-CoV-2 into Cells

A new study published on a pre-print server revealed promising results with the natural product hopeaphenol, which successfully prevented the entry of the virus into host cells. Researchers discovered plant-based stilbenoids like hopeaphenol, vatalbinoside A, and vaticanol B proved to be potent antagonists of SARS-CoV-2.

To conduct this study pseudovirus mimicking the spike proteins of B.1.1.7 and B.1.351 variants and SARS-CoV-2 main protease (Mpro) was generated. Enzymatic and cell viability assays were performed to analyze the effect of stilbenoids on SARS-CoV-2. It was observed that stilbenoids like hopeaphenol, vatalbinoside A, and vaticanol B having a tetrameric structure could selectively inhibit the SARS-CoV-2 spike RBD/host ACE2 protein interaction, with IC50 concentrations of 0.11, 0.24, and 117 0.067 μM for hopeaphenol, vatalbinoside A, and vaticanol B, respectively. The researchers found that these stilbenoids prevented the viral spike receptor-binding domain from binding to its host cell receptor and the ACE-2. It also prevented the replication of the virus in vitro without affecting the viability of the host cell.

It was also discovered that hopeaphenol and vatalbinoside A, and to a lesser extent vaticanol B, inhibit SARS-CoV-2 replication in vitro, with the efficacy of hopeaphenol at the same order of magnitude as control SARS-CoV-2 antivirals like remdesivir. Hopeaphenol blocked SARS-CoV-2 replication after 4 days with a calculated EC50 of 10.2 μM. Hopeaphenol could effectively inhibit SARS-CoV-2 variants B.1.1.7 and B.1.351 with an EC50 of 14.8 μM and IC50 of 2.3 μM respectively. Hopeaphenol, vatalbinoside A, and vaticanol B at a higher concentration of 50 μM could also inhibit the entry of SARS-CoV-2 in cells.

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