Both Baicalein and Gallocatechin Gallate Effectively Inhibit SARS-CoV-2 Replication by Targeting M pro and Sepsis in Mice

The emergence of severe acute syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to the global COVID-19 pandemic. Although the symptoms of most COVID-19 patients are mild or self-curable, most of severe patients have sepsis caused by cytokine storms, which greatly increases the case fatality rate. Moreover, there is no effective drug that can limit the novel coronavirus thus far, so it is more needed to develop antiviral drugs for the SARS-CoV-2. In our research, we employed the techniques of molecular docking to screen 35 flavonoid compounds among which 29 compounds have Z-scores lower than − 6. Then, ( −)-gallocatechin gallate, ( +)-gallocatechin and baicalein were identified to have potent inhibitory activity against SARS-CoV-2 M pro with IC 50 values of 5.774 ± 0.805 μM, 13.14 ± 2.081 μM and 5.158 ± 0.928 μM respectively by FRET assay. Molecular docking results also showed that ( −)-gallocatechin gallate, ( +)-gallocatechin and baicalein can non-covalently bind to M pro through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of ( −)-gallocatechin gallate and baicalein on cytokine storms using a mouse model of sepsis. ( −)-Gallocatechin gallate and baicalein significantly reduced sepsis of mouse models on weight, murine sepsis score, and survival rate and reduced the inflammatory factor levels, such as TNF-α, IL-1α, IL-4, and IL-10. Overall, ( −)-gallocatechin gallate and baicalein show certain potential of treatment against COVID-19.