RESUMO
Cantagalo virus (CTGV) is the etiologic agent of a pustular disease in dairy cows and dairy workers in Brazil with important economical and occupational impacts. Nevertheless, no antiviral therapy is currently available. ST-246 is a potent inhibitor of orthopoxvirus egress from cells and has proved its efficacy in cell culture and in animal models. In this work, we evaluated the effect of ST-246 on CTGV replication. Plaque reduction assays indicated that CTGV is 6-38 times more susceptible to the drug than VACV-WR and cowpox virus, respectively, with an EC50 of 0.0086µM and a selective index of >11,600. The analysis of ß-gal activity expressed by recombinant viruses in the presence of ST-246 confirmed these results. In addition, ST-246 had a greater effect on the reduction of CTGV spread in comet tail assays and on the production of extracellular virus relative to VACV-WR. Infection of mice with CTGV by tail scarification generated primary lesions at the site of scarification that appeared less severe than those induced by VACV-WR. Animals infected with CTGV and treated with ST-246 at 100mg/kg for 5days did not develop primary lesions and virus yields were inhibited by nearly 98%. In contrast, primary lesions induced by VACV-WR were not affected by ST-246. The analysis of F13 (p37) protein from CTGV revealed a unique substitution in residue 217 (D217N) not found in other orthopoxviruses. Construction of recombinant VACV-WR containing the D217N polymorphism did not lead to an increase in the susceptibility to ST-246. Therefore, it is still unknown why CTGV is more susceptible to the antiviral effects of ST-246 compared to VACV-WR. Nonetheless, our data demonstrates that ST-246 is a potent inhibitor of CTGV replication that should be further evaluated as a promising anti-CTGV therapy.
Assuntos
Antivirais/farmacologia , Benzamidas/farmacologia , Doenças dos Bovinos/virologia , Isoindóis/farmacologia , Orthopoxvirus/efeitos dos fármacos , Infecções por Poxviridae/veterinária , Sequência de Aminoácidos , Animais , Bovinos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Orthopoxvirus/química , Orthopoxvirus/genética , Orthopoxvirus/fisiologia , Infecções por Poxviridae/tratamento farmacológico , Alinhamento de Sequência , Proteínas Virais/química , Proteínas Virais/genética , Replicação Viral/efeitos dos fármacosRESUMO
Among pediatric and adult providers, 70% preferred trimethoprim-sulfamethoxazole for directed treatment of community-associated methicillin-resistant Staphylococcus aureus skin and soft-tissue infections, although a higher proportion of pediatric compared with adult providers favored clindamycin (36% vs 8%, respectively, P < .0001). For recurrent infections, 88% of providers employed at least 1 topical decolonization strategy.