The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening

Chen, Guan-Yu; Yao, Tsung-You; Ahmed, Azaj; Pan, Yi-Cheng; Yang, Juan-Cheng; Wu, Yang-Chang

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.