ABSTRACT
Diabetes is considered to be one of the diseases most associated with COVID-19. In this study, interfering effects and potential mechanisms of several compounds from Lianqiao (Forsythia suspensa (Thunb.) Vahl) leaves on the bioactivities of some key proteins of COVID-19 and its variants, as well as diabetic endothelial dysfunctions were illuminated through in vitro and in silico analyses. Results showed that, among the main ingredients in the leaves, forsythoside A showed the strongest docking affinities with the proteins SARS-CoV-2-RBD-hACE2 of COVID-19 and its variants (Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617)), as well as neuropilin-1 (NRP1), and SARS-CoV-2 main protease (MPro) to interfere coronavirus entering into the human body. Moreover, forsythoside A was the most stable in binding to receptors in Delta (B.1.617) system. It also has good antiviral activities and drug properties and has the strongest binding force to the RBD domain of COVID-19. In addition, forsythoside A reduced ROS production in AGEs-induced EA.hy926 cells, maintained endothelial integrity, and bound closely to protein profilin-1 (PFN1) receptor. This work may provide useful knowledge for further understanding the interfering effects and potential mechanisms of compounds, especially forsythoside A, from Lianqiao leaves on the bioactivities of key proteins of COVID-19/variants in diabetes.