Involucrasins Potentially Prevents SARS-CoV-2 Infection via Inhibiting Caspase-1 Signaling in Several Variants.

The study investigates the potential of involucrasins for COVID-19 prevention through molecular docking using AutoDock Vina and molecular dynamics (MD) simulations with Gromacs 2020. Docking results revealed that involucrasins exhibit strong binding affinity to the SARS-CoV-2 Delta (B.1.617.2) and Omicron (BA.2 RBD) variants of SARS-CoV-2, as well as the angiotensin-converting enzyme 2 (ACE2) protein. MD simulations further confirmed their stable interactions with these targets. Additionally, bilayer interferometry (BLI) assays demonstrated that involucrasins effectively inhibited the binding between the receptor-binding domain (RBD) of the Delta (B.1.617.2) and Omicron (BA.2 RBD) variants and ACE2, highlighting their potential as viral entry blockers. Further immunocytochemistry (ICC) and pseudo-typed lentiviral particle assay indicated that the entry of the SARS-CoV-2 Delta (B.1.617.2) and Omicron (BA.2 RBD) variants into host cells was impeded due to the inhibition of the binding of the spike (S) protein to ACE2 by involucrasins. ROS can contribute to the activation of the caspase-1 signaling pathway through their involvement in inflammasome activation. Involucrasins have an inhibitory effect on ROS generation in response to LPS/ATP stimulation. Meantime, involucrasins reduce the level of caspase-1, IL-1β, and IL-33.