Sisunatovir (RV521) is an orally bioavailable inhibitor of 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. RV521 was identified as part of a project that encompassed collaborations with several contract organizations; collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through pre-clinical and clinical evaluation. RSV521 exhibited a mean IC50 of 1.2nM 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.
The European Laboratory Research & Innovation Group
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