7KQD

Prefusion RSV F Bound to RV521

7KQD の概要

• エントリーDOI: 10.2210/pdb7kqd/pdb
• 分子名称: Fusion glycoprotein F0, 1'-{[5-(aminomethyl)-1-(4,4,4-trifluorobutyl)-1H-benzimidazol-2-yl]methyl}-6'-fluorospiro[cyclopropane-1,3'-indol]-2'(1'H)-one, SULFATE ION (3 entities in total)
• 機能のキーワード: ds-cav1, rsv f, inhibitor, viral protein
• 由来する生物種: Respiratory syncytial virus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64241.16

構造登録者

McLellan, J.S. (登録日: 2020-11-14, 公開日: 2021-04-21, 最終更新日: 2024-11-20)

主引用文献

Cockerill, G.S.,Angell, R.M.,Bedernjak, A.,Chuckowree, I.,Fraser, I.,Gascon-Simorte, J.,Gilman, M.S.A.,Good, J.A.D.,Harland, R.,Johnson, S.M.,Ludes-Meyers, J.H.,Littler, E.,Lumley, J.,Lunn, G.,Mathews, N.,McLellan, J.S.,Paradowski, M.,Peeples, M.E.,Scott, C.,Tait, D.,Taylor, G.,Thom, M.,Thomas, E.,Villalonga Barber, C.,Ward, S.E.,Watterson, D.,Williams, G.,Young, P.,Powell, K.
Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion.
J.Med.Chem., 64:3658-3676, 2021

PubMed Abstract: RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC of 1.2 nM against a panel of RSV A and B laboratory strains and clinical isolates with antiviral efficacy in the Balb/C mouse model of RSV infection. Oral bioavailability in preclinical species ranged from 42 to >100% with evidence of highly efficient penetration into lung tissue. In healthy adult human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a significant reduction in viral load and symptoms compared to placebo.

PubMed: 33729773
DOI: 10.1021/acs.jmedchem.0c01882

実験手法

X-RAY DIFFRACTION (2.94 Å)