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Antiviral Res ; 97(3): 301-11, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23257396

ABSTRACT

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.


Subject(s)
Antiviral Agents/pharmacology , Benzamides/pharmacology , Cattle Diseases/virology , Isoindoles/pharmacology , Orthopoxvirus/drug effects , Poxviridae Infections/veterinary , Amino Acid Sequence , Animals , Cattle , Female , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Molecular Sequence Data , Orthopoxvirus/chemistry , Orthopoxvirus/genetics , Orthopoxvirus/physiology , Poxviridae Infections/drug therapy , Sequence Alignment , Viral Proteins/chemistry , Viral Proteins/genetics , Virus Replication/drug effects
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