Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting Mpro and Ameliorates Pulmonary Inflammation

Ting Xiao; Mengqi Cui; Caijuan Zheng; Ming Wang; Ronghao Sun; Dandi Gao; Jiali Bao; Shanfa Ren; Bo Yang; Jianping Lin; Xiaoping Li; Dongmei Li; Cheng Yang; Honggang Zhou

doi:10.3389/fphar.2021.669642

Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting M^pro and Ameliorates Pulmonary Inflammation

Front Pharmacol. 2021 Jun 17:12:669642. doi: 10.3389/fphar.2021.669642. eCollection 2021.

Authors

Ting Xiao^{1

2}, Mengqi Cui^{1

2}, Caijuan Zheng¹, Ming Wang¹, Ronghao Sun¹, Dandi Gao^{1

2}, Jiali Bao^{1

2}, Shanfa Ren^{1

2}, Bo Yang³, Jianping Lin¹, Xiaoping Li³, Dongmei Li¹, Cheng Yang^{1

2}, Honggang Zhou^{1

2}

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, Tianjin, China.
² Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
³ Department of Thoracic Surgery, Tianjin First Central Hospital, Nankai University, Tianjin, China.

Abstract

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 IC₅₀ 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.

Keywords: 3CLpro (Mpro); COVID-19; SARS-CoV-2; myricetin; pulmonary inflammation.