Investigation of some plant stilbenoids and their fragments for the identification of inhibitors of SARS-CoV-2 viral spike/ACE2 protein binding

In silico binding studies were conducted on the known plant-derived polyphenolic tetrameric stilbenoids, (–)-hopeaphenol (1), vaticanol B (2) and vatalbinoside A (3) and their monomeric derivative resveratrol (8), identified from several plant species. The natural products (NPs) 1–3 had been previously evaluated against the SARS-CoV-2 protein targets responsible for viral transmission and infection. The two isomeric compounds (–)-hopeaphenol and vaticanol B had displayed a high affinity for blocking the binding of the SARS-CoV-2 viral spike with the human angiotensin-converting enzyme 2 (ACE2). Molecular docking and molecular dynamics simulations have been used to attempt to explain the affinity of the compounds to the spike/ACE2 complex. The hydrophobic properties of the respective target sites were computed and compared with the physicochemical properties of the NPs to explain the affinity of each compound toward the target site. Molecular docking and computed ADMET/DMPK profiles were also used to demonstrate the potential of the NPs and their fragments as possible lead compounds for antiviral discovery. These results support the experimental data obtained to date on 1–3 and clearly identify the stilbenoid structure class as one worthy of future studies during chemical biology and/or drug discovery antiviral efforts.