8HI9

SARS-CoV-2 3CL protease (3CLpro) in complex with Robinetin

Summary for 8HI9

• Entry DOI: 10.2210/pdb8hi9/pdb
• Descriptor: 3C-like proteinase nsp5, 3,7-bis(oxidanyl)-2-[3,4,5-tris(oxidanyl)phenyl]chromen-4-one (3 entities in total)
• Functional Keywords: mpro, viral protein-inhibitor complex, viral protein/inhibitor
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 2
• Total formula weight: 68255.57

Authors

Su, H.X.,Xie, H.,Li, M.J.,Xu, Y.C. (deposition date: 2022-11-19, release date: 2023-10-25, Last modification date: 2023-11-01)

Primary citation

Kruger, N.,Kronenberger, T.,Xie, H.,Rocha, C.,Pohlmann, S.,Su, H.,Xu, Y.,Laufer, S.A.,Pillaiyar, T.
Discovery of Polyphenolic Natural Products as SARS-CoV-2 M pro Inhibitors for COVID-19.
Pharmaceuticals, 16:-, 2023

PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 M. Several compounds were discovered to inhibit M at low micromolar concentrations. It was possible to crystallize robinetin together with SARS-CoV-2 M, and the X-ray structure revealed covalent interaction with the protease's catalytic Cys145 site. Selected potent molecules also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.

PubMed: 37259339
DOI: 10.3390/ph16020190

Experimental method

X-RAY DIFFRACTION (2.28 Å)