Antiviral and lung protective activity of a novel RSV fusion inhibitor in a mouse model
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
The European respiratory journal. - Copenhagen
, p. 401-408
University of Antwerp
Respiratory syncytial virus (RSV) causes bronchiolitis in young children and common colds in adults. There is no licensed vaccine, and prophylactic treatment with palivizumab is very expensive and limited to high risk infants. Ribavirin is used as an antiviral treatment in infants and immunosuppressed patients, and its use is limited due to side effects, toxicity to the recipient and staff and evidence of marginal clinical efficacy. We therefore studied the in vivo kinetics, antiviral and protective properties of a novel candidate for RSV disease treatment. The drug is a small molecule (TMC353121) discovered by screening for fusion inhibitory properties against RSV in a cellular infection model. The pharmacokinetics of TMC353121 was studied in BALB/c mice and antiviral effects determined by testing viral loads in lung tissue by quantitative RT-PCR and plaque assay after intranasal RSV infection. At doses between 0.2510 mg·kg−1, TMC353121 significantly reduced viral load, BAL cell accumulation and the severity of lung histopathological change after infection. Treatment remained effective if started within 48 hours post-infection, but was ineffective thereafter. Therefore, TMC353121 is a novel potent antiviral drug, in vivo reducing RSV replication and inhibiting consequential lung inflammation, with a great potential for further clinical development.