The coronavirus disease 2019 (COVID-19) has spread widely around the world and has seriously affected the human health of tens of millions of people. In view of lacking anti-virus drugs target to SARS-CoV-2, there is an urgent need to develop effective new drugs. In this study, we reported our discovery of SARS-CoV-2 M pro inhibitors. We selected 15 natural compounds, including 7 flavonoids, 3 coumarins, 2 terpenoids, one henolic, one aldehyde and one steroid compound for molecular docking and enzymatic screening. Myricetin were identified to have potent inhibit activity with IC 50 3.684 ± 0.076 μM in the enzyme assay. The binding pose of Myricetin with SARS-CoV-2 M pro was identified using molecular docking method. In the binding pocket of SARS-CoV-2 M pro , the chromone ring of Myricetin interacts with His41 through π -π stacking, and the 3’-, 4’- and 7-hydroxyl of Myricetin interact with Phe140, Glu166and Asp187 through hydrogen bonds. Significantly, our results showed that Myricetin has potent effect on bleomycin-induced pulmonary inflammation by inhibiting the infiltration of inflammatory cells and the secretion of inflammatory cytokines IL-6, IL-1α, TNF-α and IFN-γ. Overall, Myricetin may be a potential drug for anti-virus and symptomatic treatment of COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, myricetin, pulmonary inflammation, 3CLpro (Mpro), 【초록키워드】 coronavirus disease, drugs, molecular docking, drug, inhibitors, Spread, Health, Symptomatic treatment, IFN-γ, binding, TNF-α, compounds, infiltration, inflammatory cell, enzyme, secretion, M pro, binding pocket, hydrogen bonds, His41, IL-1α, effective, selected, affected, develop, reported, inhibit, interact, inhibiting, inflammatory cytokines IL-6, Phe140, 【제목키워드】 pulmonary, M pro, targeting,