Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8523276 | Antiviral Research | 2018 | 33 Pages |
Abstract
The Orthopoxvirus (OPV) genus of the Poxviridae family contains several human pathogens, including Vaccinia virus (VACV), which have been implicating in outbreaks of a zoonotic disease called Bovine Vaccinia in Brazil. So far, no approved treatment exists for OPV infections, but ST-246 and Cidofovir (CDV) are now in clinical development. Therefore, the objective of this work was to evaluate the susceptibility of five strains of Brazilian VACV (Br-VACV) to ST-246 and Cidofovir. The susceptibility of these strains to both drugs was evaluated by plaque reduction assay, extracellular virus's quantification in the presence of ST-246 and one-step growth curve in cells treated with CDV. Besides that, the ORFs F13L and E9L were sequenced for searching of polymorphisms associated with drug resistance. The effective concentration of 50% (EC50) from both drugs varies significantly for different strains (from 0.0054 to 0.051â¯Î¼M for ST-246 and from 27.14 to 61.23â¯Î¼M for CDV). ST-246 strongly inhibits the production of extracellular virus for all isolates in concentrations as low as 0.1â¯Î¼M and it was observed a relevant decrease of progeny production for all Br-VACV after CDV treatment. Sequencing of the F13L and E9L ORFs showed that Br-VACV do not present the polymorphism(s) associated with resistance to ST-246 and CDV. Taken together, our results showed that ST-246 and CDV are effective against diverse, wild VACV strains and that the susceptibility of Br-VACV to these drugs mirrored the phylogenetic split of these isolates into two groups. Thus, both ST-246 and CDV are of great interest as compounds to treat individuals during Bovine Vaccinia outbreaks in Brazil.
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Virology
Authors
Mariana A. Pires, Nathália F.S. Rodrigues, Danilo B. de Oliveira, Felipe L. de Assis, Galileu B. Costa, Erna G. Kroon, Bruno E.F. Mota,