Proteases are important to the health and viability of cells and viruses, says De-Yu Xie, professor of plant and microbial biology at NC State and the corresponding author of the study. If proteases are inhibited, cells cannot perform many important functions -- like replication, for example.

"One of our lab's focuses is to find nutraceuticals in food or medicinal plants that inhibit either how a virus attaches to human cells or the propagation of a virus in human cells," Xie said.

In the study, the NC State researchers performed both computer simulations and lab studies showing how the so-called "main protease" (M^pro) in the SARS-CoV-2 virus reacted when confronted with a number of different plant chemical compounds already known for their potent anti-inflammatory and antioxidant properties.

"M^pro in SARS-CoV-2 is required for the virus to replicate and assemble itself," Xie said. "If we can inhibit or deactivate this protease, the virus will die."

Computer simulations showed that the studied chemical compounds from green tea, two varieties of muscadine grapes, cacao powder and dark chocolate were able to bind to different portions of M^pro.

"M^pro has a portion that is like a 'pocket' that was 'filled' by the chemical compounds," Xie said. "When this pocket was filled, the protease lost its important function."

In vitro lab experiments completed by Yue Zhu, an NC State Ph.D. student in Xie's lab, showed similar results. The chemical compounds in green tea and muscadine grapes were very successful at inhibiting M^pro's function; chemical compounds in cacao powder and dark chocolate reduced M^pro activity by about half.

"Green tea has five tested chemical compounds that bind to different sites in the pocket on M^pro, essentially overwhelming it to inhibit its function," Xie said. "Muscadine grapes contain these inhibitory chemicals in their skins and seeds. Plants use these compounds to protect themselves, so it is not surprising that plant leaves and skins contain these beneficial compounds."

The paper appears in Frontiers in Plant Science. Zhu is the paper's first author. The research was supported by the U.S. Department of Agriculture.

Story Source:

Materials provided by North Carolina State University. Original written by Mick Kulikowski. Note: Content may be edited for style and length.

Journal Reference:

1. Yue Zhu, De-Yu Xie. Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2. Frontiers in Plant Science, 2020; 11 DOI: 10.3389/fpls.2020.601316