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Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design.

Yuan S, Fan K, Chen Z, Sun Y, Hou H, Zhu L
Virol Sin 35 445-454 (2020)
Cited: 7 times
EuropePMC logo PMID: 32103448

Abstract

Human rhinoviruses (HRVs) are the predominant infectious agents for the common cold worldwide. The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma. 3C protease, a highly conserved enzyme, cleaves the viral polyprotein during replication and assists the virus in escaping the host immune system. These key roles make 3C protease an important drug target. A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been determined. These structures shed light on the determinants of drug specificity. Here we describe the structures of HRV-C15 3C in free and inhibitor-bound forms. The volume-decreased S1' subsite and half-closed S2 subsite, which were thought to be unique features of enterovirus A 3C proteases, appear in the HRV-C 3C protease. Rupintrivir assumes an "intermediate" conformation in the complex, which might open up additional avenues for the design of potent antiviral inhibitors. Analysis of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.

Articles - 6ku8 mentioned but not cited (3)

  1. Dual inhibition of SARS-CoV-2 and human rhinovirus with protease inhibitors in clinical development. Liu C, Boland S, Scholle MD, Bardiot D, Marchand A, Chaltin P, Blatt LM, Beigelman L, Symons JA, Raboisson P, Gurard-Levin ZA, Vandyck K, Deval J. Antiviral Res 187 105020 (2021)
  2. Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode. Lockbaum GJ, Henes M, Lee JM, Timm J, Nalivaika EA, Thompson PR, Kurt Yilmaz N, Schiffer CA. Biochemistry 60 2925-2931 (2021)
  3. Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design. Yuan S, Fan K, Chen Z, Sun Y, Hou H, Zhu L. Virol Sin 35 445-454 (2020)


Reviews citing this publication (3)

  1. Innate immune evasion mediated by picornaviral 3C protease: Possible lessons for coronaviral 3C-like protease? Ng CS, Stobart CC, Luo H. Rev Med Virol 31 1-22 (2021)
  2. Rhinovirus Inhibitors: Including a New Target, the Viral RNA. Real-Hohn A, Blaas D. Viruses 13 1784 (2021)
  3. A comprehensive update on the structure and synthesis of potential drug targets for combating the coronavirus pandemic caused by SARS-CoV-2. Malik P, Jain S, Jain P, Kumawat J, Dwivedi J, Kishore D. Arch Pharm (Weinheim) 355 e2100382 (2022)

Articles citing this publication (1)



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