9NA0

Main protease of HKU8 in complex with AVI8122

This is a non-PDB format compatible entry.

Summary for 9NA0

• Entry DOI: 10.2210/pdb9na0/pdb
• Descriptor: main protease, N-[(2S)-3-cyclopropyl-1-({(2S,3S)-3,4-dihydroxy-1-[(3S)-2-oxopiperidin-3-yl]butan-2-yl}amino)-1-oxopropan-2-yl]-7-fluoro-1H-indole-2-carboxamide (3 entities in total)
• Functional Keywords: main protease, nsp5, hku8, inhibitor, viral protein
• Biological source: Miniopterus bat coronavirus HKU8
• Total number of polymer chains: 1
• Total formula weight: 33393.90

Authors

Chen, P.,Lu, J.,Lemieux, M.J. (deposition date: 2025-02-11, release date: 2026-02-18, Last modification date: 2026-07-29)

Primary citation

Chen, P.,Strunk, U.,Arutyunova, E.,Lu, J.,Chen, S.A.,Demmon, S.,Maplethorpe, C.,Kandadai, A.S.,Shields, J.,Saffran, H.A.,Lamer, T.,Fischer, C.,Van Oers, T.J.,Turner, Z.,Leong, P.,Iyyathurai, J.,Young, H.S.,Bai, B.,Vederas, J.C.,Nieman, J.A.,Joyce, M.A.,Tyrrell, D.L.,Lemieux, M.J.
Identification of a Potent Pan-Coronaviral Main Protease Inhibitor.
J.Med.Chem., 2026

PubMed Abstract: The global impact of SARS-CoV-2 and the continued emergence of zoonotic coronaviruses underscore the urgent need for broad-spectrum antivirals for pandemic preparedness. Herein, we report , a covalent pan-coronaviral inhibitor that targets 19 Ms across the α, β, γ, and δ genera, encompassing bat, human, and other animal coronaviruses. exhibits low nanomolar potency and favorable pharmacokinetics in mice. Structural studies reveal that forms a covalent bond with the catalytic cysteine and maintains conserved interactions within the active sites of these Ms. , efficiently inhibited the replication of SARS-CoV-2 and its variants of concern as well as the activity of Ms from all four genera. Furthermore, in mouse models, conferred dose-dependent protection against a lethal SARS-CoV-2 infection. Our findings position as an early lead compound and a tractable structural starting point for the development of broad-spectrum antivirals against future coronavirus spillover threats.

PubMed: 42461134
DOI: 10.1021/acs.jmedchem.6c00645

Experimental method

X-RAY DIFFRACTION (1.8 Å)