Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion.
J Med Chem
; 64(7): 3658-3676, 2021 04 08.
Article
em En
| MEDLINE
| ID: mdl-33729773
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 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Benzimidazóis
/
Vírus Sincicial Respiratório Humano
/
Internalização do Vírus
Tipo de estudo:
Clinical_trials
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido