872141-30-5Relevant articles and documents
Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion
Cockerill, G. Stuart,Angell, Richard M.,Bedernjak, Alexandre,Chuckowree, Irina,Fraser, Ian,Gascon-Simorte, Jose,Gilman, Morgan S. A.,Good, James A. D.,Harland, Rachel,Johnson, Sara M.,Ludes-Meyers, John H,Littler, Edward,Lumley, James,Lunn, Graham,Mathews, Neil,McLellan, Jason S.,Paradowski, Michael,Peeples, Mark E.,Scott, Claire,Tait, Dereck,Taylor, Geraldine,Thom, Michelle,Thomas, Elaine,Villalonga Barber, Carol,Ward, Simon E.,Watterson, Daniel,Williams, Gareth,Young, Paul,Powell, Kenneth
supporting information, p. 3658 - 3676 (2021/04/12)
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 IC50 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.
