The activity of three anti-herpetic drugs (Acyclovir [ACV], Gancyclovir [GCV] and Foscarnet [PFA]) was tested against bovine herpesvirus 1 (BoHV-1), 2 (BoHV-2) and 5 (BoHV-5) in vitro using the plaque reduction assay. Different drug concentrations were tested against one hundred 50% tissue culture infectious dose (TCID 50 ) of the respective viruses. Drug concentrations lower than 200μg/mL resulted in viability rates of more than 80% for MDBK and Hep2 cells in the MTT test (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The selectivity index (IS) of the drugs was calculated dividing the concentration of the drug that is cytotoxic for 50% of the cells (CC 50 ) by the concentration of the drug that was effective in reducing by 50% the number of viral plaques (EC 50 ) for the three herpesviruses. Thus, ACV was shown to be moderately active against BoHV-1 (EC 50 : 112.9μg/mL; IS: 4.5), BoHV-2 (EC 50 : 114.2μg/mL; IS: 4.5) and BoHV-5 (EC 50 : 96.9μg/mL; IS: 5.3). GCV was effective against BoHV-2 (EC 50 : 33.5μg/mL; IS: 16.6), moderately effective against BoHV-5 (EC 50 : 123.2μg/mL; IS: 4.5) and poorly active against BoHV-1 (EC 50 : 335.8μg/mL; IS: 1.7). PFA exhibited the highest antiviral activity, being the only drug that, at concentration of 100μg/mL, completely inhibited plaque formation by all three viruses. PFA was the most effective in vitro against BoHV-1 (EC 50 : 29.5μg/mL; IS: 42.2), BoHV-2 (EC 50 : 45.2μg/mL; IS: 27.6) and BoHV-5 (EC 50 : 7.8μg/mL; IS: 160.6). Thus, the results indicate that PFA is a promising candidate for experimental therapeutic testing in vivo against bovine herpesviruses.INDEX TERMS: Antivirals, BoHV-1, BoHV-2, BoHV-5, Foscarnet, Gancyclovir, Acyclovir.
INTRODUÇÃOOs herpesvírus bovino tipos 1 (BoHV-1), 2 (BoHV-2) e 5 (BoHV-5) são vírus DNA de cadeia dupla linear, que possuem um capsídeo de simetria icosaédrica e envelope lipoprotéico, classificados na família Herpesviridae, subfamília Alphaherpesvirinae. Esses vírus estabelecem e reativam infecções latentes em seus hospedeiros, propriedade que permite a sua manutenção na natureza (Rock et al. 1992, Roizman 1992. O BoHV-1 e 5 pertencem ao gênero Varicellovirus, e o BoHV-2 é classificado no gêne-ro Simplexvirus (Roizman 1992). O BoHV-1 é associado com doença respiratória (rinotraqueíte infecciosa bovina, IBR), conjuntivite, vulvovaginite/balanopostite pustular infecciosa (IPV/IBP), infertilidade transitória e abortos (Roizman 1992, Kahrs 2001. O BoHV-2 é associado à mamilite herpética bovina (BHM), doença vesicular e erosiva do úbere e tetos, que acomete principalmente vacas leiteiras de primeira cria (Kahrs 2001). O BoHV-5 é o agente da meningoencefalite herpética, doença geralmente fatal em bovinos jovens, e que ocorre com frequência na Argentina e no Brasil (Carrillo et al. 1983, Rissi et al. 2006.Historicamente, os herpesvírus humanos têm sido alvo para o desenvolvimento e teste de fármacos antivirais. O Aciclovir (ACV) e o Ganciclovir (GCV) são análogos de nucleosídeos, cujas moléculas consistem de uma guanina ass...