Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.
Sussex Drug Discovery Centre, University of Sussex, Brighton, England BN1 9QJ, U.K.
J Med Chem. 2021 Apr 8;64(7):3658-3676. doi: 10.1021/acs.jmedchem.0c01882. Epub 2021 Mar 17.
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.
RV521 是一种口服生物可利用的呼吸道合胞病毒 (RSV) 融合抑制剂，它是在 Reviral 基于物理性质导向的命中分析实验的先导化合物优化过程中发现的。在优化阶段，除了在临床前和临床评估阶段使用的合作机构外，该实验还与许多合同机构合作进行了协同药物化学和病毒学研究。RV521 对一组 RSV A 和 B 实验室株和临床分离株的平均 IC 为 1.2 nM，在 RSV 感染的 Balb/C 小鼠模型中具有抗病毒疗效。在临床前物种中，口服生物利用度范围从 42%到 >100%，并且有证据表明其能够高效渗透到肺部组织中。在 RSV 实验感染的健康成年人类志愿者中，与安慰剂相比，RV521 观察到了显著的抗病毒作用，病毒载量和症状均显著降低。
