3CLp dimer binds α-Ketoamides

Stable Identifier
Reaction [omitted]
Homo sapiens
Related Species
Human SARS coronavirus
3C-like proteinase dimer binds α-Ketoamides
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The rep proteases that are essential for viral polyprotein processing by the coronaviruses and enteroviruses exhibit a strong preference for substrates containing Gln at P1 position, and share an active-site conformation that engages the substrate's P1 residue. Compound 11r and compound 13b are peptidomimetic α-ketoamides that function as high-affinity non-cleavable substrate analogues and thus exhibit antiviral activity against dimeric 3C-like proteinases (C3Lp dimer) of coronaviruses and enteroviruses (Chen et al. 2005, Zhang et al. 2020). Their clinical safety and efficacy in COVID-19 are under investigation.

Literature References
PubMed ID Title Journal Year
15507456 Severe acute respiratory syndrome coronavirus 3C-like proteinase N terminus is indispensable for proteolytic activity but not for enzyme dimerization. Biochemical and thermodynamic investigation in conjunction with molecular dynamics simulations

Chen, S, Shen, X, Chen, L, Tan, J, Jiang, H, Du, L, Chen, K, Shen, J, Sun, T, Chen, J

J. Biol. Chem. 2005
32045235 α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment

Hilgenfeld, R, Wang, J, von Brunn, A, Neyts, J, Zhang, L, Leyssen, P, Snijder, EJ, Lanko, K, Kusov, Y, Liu, H, Ma, Q, Nian, Y, de Wilde, A, Lin, D

J. Med. Chem. 2020
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
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