2. Academic Validation
  3. Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor

Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor

  • J Med Chem. 2019 Jul 11;62(13):6003-6014. doi: 10.1021/acs.jmedchem.9b00654.
Xiufang Zheng 1,  Lu Gao 1,  Lisha Wang 1,  Chungen Liang 1,  Baoxia Wang 1,  Yongfu Liu 1,  Song Feng 1,  Bo Zhang 1,  Mingwei Zhou 1,  Xin Yu 1,  Kunlun Xiang 1,  Li Chen 1,  Tao Guo 2,  Hong C Shen 1,  Gang Zou 3,  Jim Zhen Wu 3,  Hongying Yun 1
Affiliations

Affiliations

  • 1 Roche Pharma Research and Early Development , Roche Innovation Center Shanghai , Building 5, 720 Cailun Road , Shanghai 201203 , China.
  • 2 International Discovery Service Unit, Research Service Division , WuXi AppTec (Shanghai) Co., Ltd. , Lane 31, Yiwei Road, Waigaoqiao , Shanghai , 200131 , China.
  • 3 Ark Biosciences Inc. , 780 Cailun Road, Suite 701, ZhangJiang Hitech Park, Pudong , Shanghai 201203 , China.
PMID: 31194544 DOI: 10.1021/acs.jmedchem.9b00654
Abstract

Ziresovir (RO-0529, AK0529) is reported here for the first time as a promising respiratory syncytial virus (RSV) fusion (F) protein inhibitor that currently is in phase 2 clinical trials. This article describes the process of RO-0529 as a potent, selective, and orally bioavailable RSV F protein inhibitor and highlights the in vitro and in vivo anti-RSV activities and pharmacokinetics in animal species. RO-0529 demonstrates single-digit nM EC50 potency against laboratory strains, as well as clinical isolates of RSV in cellular assays, and more than one log viral load reduction in BALB/c mouse model of RSV viral Infection. RO-0529 was proven to be a specific RSV F protein inhibitor by identification of drug resistant mutations of D486N, D489V, and D489Y in RSV F protein and the inhibition of RSV F protein-induced cell-cell fusion in cellular assays.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-109142
    RSV F Inhibitor
    RSV