Simultaneous Inhibition of SARS-CoV-2 Infectivity by a Specific Combination of Plant-derived Compounds

SARS-CoV-2 pandemic remains a challenge to human health and economy worldwide. Previously we have shown that a combination of active plant-derived compounds and plant extracts can dose-dependently inhibit binding of RBD-spike protein SARS-CoV-2 to the ACE2 receptor and its expression on human alveolar epithelial cells. Here we use eGFP-luciferase-SARS-CoV-2 spike protein pseudo-virions and SARS-CoV-2-RdRp, to show if the antiviral effectiveness of this combination of plant-derived compounds and plant extracts expands to other important key mechanisms of SARS-CoV-2 infection. Or results revealed that this combination of five plant-derived compounds inhibited the attachment of the SARS-CoV-2 pseudo-typed particles with lung hACE2/A549 cells. In addition, it down-regulated the activity of key enzymes known to be crucial for the entry of the SARS-CoV-2 virus, such as TMPRSS2, furin and cathepsin L, but not their expression at protein level. This combination did not affect ACE2 binding to and ACE2 enzymatic activity, but modestly decrease cellular expression of neuropilin-1 molecule and significantly inhibited activity of viral RdRp. This study demonstrates inhibitory effects of this combination on key cellular mechanisms of SARS-CoV-2 infection. The findings further support the use of plant-derived compounds as effective health measures against SARS-CoV-2-caused infection.