5FX6

Novel inhibitors of human rhinovirus 3C protease

Summary for 5FX6

• Entry DOI: 10.2210/pdb5fx6/pdb
• Related: 5FX5
• Descriptor: RHINOVIRUS 3C PROTEASE, ethyl (4R)-4-[[(2S,4S)-1-[(2S)-3-methyl-2-[(5-methyl-1,2-oxazol-3-yl)carbonylamino]butanoyl]-4-phenyl-pyrrolidin-2-yl]carbonylamino]-5-[(3S)-2-oxidanylidenepyrrolidin-3-yl]pentanoate (3 entities in total)
• Functional Keywords: transferase
• Biological source: HUMAN RHINOVIRUS 2 (HRV2)
• Cellular location: Capsid protein VP0: Virion . Capsid protein VP4: Virion . Capsid protein VP2: Virion . Capsid protein VP3: Virion . Capsid protein VP1: Virion . Protein 2B: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 2C: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3A: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3AB: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Viral protein genome-linked: Virion . Protease 3C: Host cytoplasm . Protein 3CD: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . RNA-directed RNA polymerase: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side : P04936
• Total number of polymer chains: 1
• Total formula weight: 20735.51

Authors

Kawatkar, S.,Ek, M.,Hoesch, V.,Gagnon, M.,Nilsson, E.,Lister, T.,Olsson, L.,Patel, J.,Yu, Q. (deposition date: 2016-02-24, release date: 2016-06-22, Last modification date: 2024-11-13)

Primary citation

Kawatkar, S.P.,Gagnon, M.,Hoesch, V.,Tiong-Yip, C.,Johnson, K.,Ek, M.,Nilsson, E.,Lister, T.,Olsson, L.,Patel, J.,Yu, Q.
Design and Structure-Activity Relationships of Novel Inhibitors of Human Rhinovirus 3C Protease.
Bioorg.Med.Chem.Lett., 26:3248-, 2016

PubMed Abstract: Human rhinovirus (HRV) is a primary cause of common cold and is linked to exacerbation of underlying respiratory diseases such as asthma and COPD. HRV 3C protease, which is responsible for cleavage of viral polyprotein in to proteins essential for viral life-cycle, represents an important target. We have designed proline- and azetidine-based analogues of Rupintrivir that target the P2 pocket of the binding site. Potency optimization, aided with X-ray crystallography and quantum mechanical calculations, led to compounds with activity against a broad spectrum of HRV serotypes. Altogether, these compounds represent alternative starting points to identify promising leads in our continual efforts to treat HRV infections.

PubMed: 27265257
DOI: 10.1016/J.BMCL.2016.05.066

Experimental method

X-RAY DIFFRACTION (1.45 Å)