6FFS

Structure-based design and synthesis of macrocyclic human rhinovirus 3C protease inhibitors

Summary for 6FFS

• Entry DOI: 10.2210/pdb6ffs/pdb
• Descriptor: 3C Protease, ~{N}-[(2~{S},5~{S},14~{S})-2-[(4-fluorophenyl)methyl]-5-(hydroxymethyl)-9-methyl-3,8,15-tris(oxidanylidene)-1,4,9-triazacyclopentadec-14-yl]-5-methyl-1,2-oxazole-3-carboxamide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: 3c protease, rhinovirus, inhibitor, hydrolase
• Biological source: Human rhinovirus 2 (HRV-2)
• 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: 20753.43

Authors

Wiesmann, C.,Farady, C. (deposition date: 2018-01-09, release date: 2018-02-21, Last modification date: 2024-01-17)

Primary citation

Namoto, K.,Sirockin, F.,Sellner, H.,Wiesmann, C.,Villard, F.,Moreau, R.J.,Valeur, E.,Paulding, S.C.,Schleeger, S.,Schipp, K.,Loup, J.,Andrews, L.,Swale, R.,Robinson, M.,Farady, C.J.
Structure-based design and synthesis of macrocyclic human rhinovirus 3C protease inhibitors.
Bioorg. Med. Chem. Lett., 28:906-909, 2018

PubMed Abstract: The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor 10 with sub-micromolar antiviral activity.

PubMed: 29433930
DOI: 10.1016/j.bmcl.2018.01.064

Experimental method

X-RAY DIFFRACTION (1.86 Å)