Activity of three antiviral drugs against bovine herpesviruses 1, 2 and 5 in cell culture

Pesquisa Veterinária Brasileira

Weiblen, Rudi¹  Silva, Sara C. da³  Flores, Eduardo F¹  Kreutz, Luiz C²  Dezengrini, Renata³  Weiss, Marcelo³ 

[1] UFSM, Santa Maria, Brasil;Universidade de Passo Fundo, Passo Fundo, Brasil;Universidade Federal de Santa Maria (UFSM),, Santa Maria, Brasil

关键词: Antivirals;    BoHV-1;    BoHV-2;    BoHV-5;    Foscarnet;    Gancyclovir;    Acyclovir. RESUMO A atividade de três fármacos antivirais (Aciclovir [ACV];    Ganciclovir [GCV] e Foscarnet [PFA]) foi testada in vitro frente aos herpesvírus bovino tipos 1 (BoHV-1);    2 (BoHV-2) e 5 (BoHV-5). Para isso;    utilizou-se o teste de reducao de placas virais em cultivo celular;    testando-se diferentes concentracoes dos farmacos frente a 100 doses infectantes para 50% dos cultivos celulares (DICC50) dos respectivos virus. Pelo teste de MTT (3-(4;    5-Dimethylthiazol- 2-yl)-2;    5-diphenyltetrazolium bromide);    verificou-se que concentracoes inferiores a 200ƒÊg/mL dos tres antivirais resultaram em indices de viabilidade de celulas MDBK e Hep2 superiores a 80%. Com base na concentracao citotoxica para 50% das celulas (CC50) e na concentracao dos farmacos efetiva para inibir em 50% o numero de placas virais (EC50);    calculou-se o indice de seletividade (IS) dos antivirais para os tres herpesvirus. Assim;    o ACV demonstrou ser moderadamente ativo frente ao BoHV-1 (EC50: 112;    9ƒÊg/mL e IS: 4;    5);    ao BoHV-2 (EC50: 114;    2 ƒÊg/mL e IS: 4;    5) e BoHV-5 (EC50: 96;    9ƒÊg/mL e IS: 5;    3). O GCV apresentou atividade moderada frente ao BoHV-2 (EC50: 33;    5ƒÊg/mL e IS: 16;    6) e;    em menor grau;    contra o BoHV-5 (EC50: 123;    2ƒÊg/mL e IS: 4;    5);    sendo ineficaz frente ao BoHV-1 (EC50: 335;    8ƒÊg/mL e IS: 1;    7). O PFA apresentou atividade antiviral mais pronunciada;    sendo o unico farmaco que;    na concentracao de 100ƒÊg/mL;    inibiu completamente a producao de placas pelos tres virus testados. O PFA foi o mais efetivo in vitro frente ao BoHV-1 (EC50: 29;    5ƒÊg/mL e IS: 42;    2);    ao BoHV-2 (EC50: 45;    2ƒÊg/mL e IS: 27;    6) e ao BoHV-5 (EC50: 7;    8ƒÊg/mL e IS: 160;    6). Portanto;    os resultados obtidos indicam que o PFA pode se constituir em um candidato para terapia experimental de infeccoes pelos herpesvirus de bovinos in vivo. TERMOS DE INDEXAÇÃO: Antivirais;    BoHV-1;    BoHV-2;    BoHV5;    Foscarnet;    Ganciclovir;    Aciclovir.;   

DOI  :  10.1590/S0100-736X2010001000008

来源: Colegio Brasileiro de Patologia Animal-CBPA

【 摘 要 】

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 (TCID50) 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 (CC50) by the concentration of the drug that was effective in reducing by 50% the number of viral plaques (EC50) for the three herpesviruses. Thus, ACV was shown to be moderately active against BoHV-1 (EC50: 112.9μg/mL; IS: 4.5), BoHV-2 (EC50: 114.2μg/mL; IS: 4.5) and BoHV-5 (EC50: 96.9μg/mL; IS: 5.3). GCV was effective against BoHV-2 (EC50: 33.5μg/mL; IS: 16.6), moderately effective against BoHV-5 (EC50: 123.2μg/mL; IS: 4.5) and poorly active against BoHV-1 (EC50: 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 (EC50: 29.5μg/mL; IS: 42.2), BoHV-2 (EC50: 45.2μg/mL; IS: 27.6) and BoHV-5 (EC50: 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

【 授权许可】

CC BY-NC