📄 Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1

The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes such as the common cold, bronchitis, and pneumonia. The CoV main protease (Mpro), which is a key enzyme in viral replication via the proteolytic processing of the replicase polyproteins, has been recognized as an attractive target for rational drug design. In this study, we report the structure of HCoV-HKU1 Mpro in complex with a Michael acceptor, inhibitor N3. The structure of HCoV-HKU1 provides a high-quality model for group 2A Co. Vs, which are distinct from group 2B Co. Vs such as severe acute respiratory syndrome CoV. The structure, together with activity assays, supports the relative conservation at the P1 position that was discovered by sequencing the HCoV-HKU1 genome. Combined with structural data from other CoV Mpros, the HCoV-HKU1 Mpro structure reported here provides insights into both substrate preference and the design of antivirals targeting Co. Vs. Copyright © 2008, American Society for Microbiology.

keywords 🔗 severe acute (1373) 🔗 main protease (44) 🔗 drug design (36) 🔗 human coronavirus (623) 🔗 respiratory syndrome (2004) 🔗 acute respiratory (1734) 🔗 viral replication (258)

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