Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular

Dezengrini, Renata; Silva, Sara C. da; Weiss, Marcelo; Kreutz, Luiz Carlos; Weiblen, Rudi; Flores, Eduardo Furtado

doi:10.1590/s0100-736x2010001000008

Cited by 7 publications

(4 citation statements)

References 21 publications

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“…The PFA reduced the number of viral plaques, but presented the highest indexes of EC 50 and lower SI for the EHV-1. These results differed from those obtained by DEZENGRINI et al (2010), in which PFA presented the better results against BoHV-1, BoHV-2 and BoHV-5. Against EHV-1, in vitro antiviral activity and SI presented by PFA were lower than the other drugs tested, indicating that this drug should not be considered the main alternative for therapies and in vivo studies.…”

Section: Resultscontrasting

confidence: 99%

“…The value obtained in SI allowed estimating drug safety level for use in animals. The higher is the value (above 1), more significant will be the difference between the antiviral dose necessary to reduce in 50% the virus replication (EC 50 ) and cytotoxic dose (CC 50 ); therefore, safer the drug for use in animals (COEN & RICHMAN, 2007;DEZENGRINI et al, 2010).…”

Section: Plaque Reduction Assays (Pra)mentioning

confidence: 99%

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In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

et al. 2018

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Equid alphaherpesvirus type 1 (EHV-1) is distributed worldwide and is a major agent of abortion, respiratory and neurological disease in horses. No specific treatment is available for EHV-1 infection, yet the potential of antiviral therapy has been explored. In this study we investigated the in vitro activity of Acyclovir, Ganciclovir, Foscarnet, Famciclovir, Vidarabina and Cidofovir against EHV-1. For this, the MTT test was performed, in which all the tested drugs showed no toxicity up to 200μg/mL. Subsequently, different drug concentrations were submitted to viral plaque reduction assays in cell culture. The selectivity index (SI) of the compounds was determined using the cytotoxic concentration for 50% of cells (CC50), obtained by MTT, and effective drug concentration to inhibit by 50% the number of viral plaques (EC50). Ganciclovir (SI: 490; EC50: 1.9 μg/mL) was the most efficient and safest drug against EHV-1, followed by Cidofovir (SI: 150, EC50: 5.7μg/mL), Acyclovir (SI: 37.4, EC50: 22.2μg/mL), Famciclovir (SI: 25.1, EC50: 24.5μg/mL), Vidarabine (SI: 12.2, EC50: 40.9μg/mL) and Foscarnet (SI: 6.9, EC50: 49.5 μg/mL), respectively. These results indicated that Ganciclovir (followed by Cidofovir), is a promising candidate for use in in vivo experiments.

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Section: Resultscontrasting

confidence: 99%

Section: Plaque Reduction Assays (Pra)mentioning

confidence: 99%

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

et al. 2018

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“…Second, the biological and genetic similarity of BoHV-2 with human simplex viruses may be exploited for the research and development of pharmaceuticals and vaccines as well. In this sense, BoHV-2 has been proposed as a potential target/model for the development of anti-herpetic drugs (Field et al 2006, Dezengrini et al 2010, Torres et al 2010). Third, animal herpesviruses have been long proposed as potential platforms for vaccine delivery and a number of current animal vaccines are based on herpesvirus vectors (Verma & Weitzman 2005, Kanekiyo et al 2019.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of Bovine alphaherpesvirus 2 in calves following different routes of inoculation

et al. 2020

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Bovine alphaherpesvirus 2 (BoHV-2) is the agent of herpetic mammilitis (BHM), a cutaneous and self-limiting disease affecting the udder and teats of cows. The pathogenesis of BoHV-2 is pourly understood, hampering the development of therapeutic drugs, vaccines and other control measures. This study investigated the pathogenesis of BoHV-2 in calves after inoculation through different routes. Three- to four-months seronegative calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscular (IM, n=4), intravenous (IV, n=4) or transdermal (TD) after mild scarification (n=4) and submitted to virological, clinical and serological monitoring. Calves inoculated by the IV route presented as light increase in body temperature between days 6 to 9 post-inoculation (pi). Virus inoculation by the TD route resulted in mild inflammatory lesions at the sites of inoculation, characterized by hyperemia, small vesicles, mild exudation and scab formation, between days 2 and 8pi. Virus or viral DNA was detected by PCR in the crusts/swabs collected from lesions of 3 out of 4 animals inoculated TD from day 2 to 8pi. Viremia was detected in 3/4 animals of the IM group (from day 4 to 8pi); in 2/4 animals of the IV group (days 6 and 8pi) but not in the TD group. Calves from all inoculated groups seroconverted to BoHV-2 in titers from 4 to 64, as indicated by virus-neutralizing (VN) assays performed in sera collected at day 15pi. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation as indicated by lack of virus detection in the blood and/or in inoculation sites and no increase in VN antibody titers. These results demonstrated that BoHV-2 was able to replicate efficiently in calves following different routes of exposure, produced viremia after IM and IV inoculation and was not reactivated by Dex treatment.

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“…A number of drugs have been successfully used for the treatment of herpetic infections in humans, yet their use in veterinary medicine is still incipient (De Clercq 2008, Razonable 2011, Maxwell 2017. However, some studies investigated the antiviral action of drugs against bovine herpesviruses (1, 2 and 5) (Dezengrini et al 2010), felid herpesvirus (Thomasy & Maggs 2016) and herpesviruses of horses (Vissani et al 2015, Oliveira et al 2018. These drugs may have important applications in equine medicine by reducing the clinical consequences of herpetic infections (Garré et al 2008, Carmichael et al 2013, Glorieux et al 2012, Maxwell et al 2008, Maxwell 2017.…”

Section: Introductionmentioning

confidence: 99%

Ganciclovir attenuates the respiratory disease induced by Equid alphaherpesvirus 1 in rabbits

et al. 2019

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Equid alphaherpesvirus 1 (EHV-1) is an important pathogen of horses, associated with respiratory, neurological disease and abortions. As vaccination is not always effective, anti-herpetic therapy may represent an alternative to prevent the losses caused by the infection. We herein investigated the activity of ganciclovir (GCV), an anti-herpetic human drug, in rabbits experimentally infected with EHV-1. Thirty-days-old New Zealand rabbits were allocated in three groups (6 animals each) and submitted to different treatments: G1 (non-infected controls), G2 (inoculated with EHV-1) - 107 TCID50 intranasally - IN) and G3 (inoculated IN with EHV-1 and treated with GCV - 5mg/kg/day for 7 days) and monitored thereafter. All animals of G2 developed systemic signs (moderate to severe apathy, anorexia), ocular discharge and respiratory signs (serous to mucopurulent nasal discharge), including mild to severe respiratory distress. Viremia was detected in all rabbits of G2 for up to 11 days (mean duration = 6.5 days). One animal died after severe respiratory distress and neurological signs (bruxism, opistotonus). In addition, these animals gained less weight than the control (G1) and GCV-treated rabbits (G3) from days 4 to 14pi (p<0.05). The clinical score of rabbits of G2 was statistically higher than the other groups from days 3 to 6pi (p<0.05), demonstrating a more severe disease. In contrast, G3 rabbits did not present systemic signs, presented only a mild and transient nasal secretion and gained more weight than G2 animals (p<0.05). In addition, viremia was detected in only 3 rabbits and was transient (average of 2.3 days). Thus, administration of GCV to rabbits inoculated IN with EHV-1 resulted in an important attenuation of the clinical disease as demonstrated by full prevention of systemic signs, maintenance of weight gain and by drastic reduction in viremia and in the magnitude of respiratory signs. These results are promising towards further testing of GCV as a potential drug for anti-herpetic therapy in horses.

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Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular

Cited by 7 publications

References 21 publications

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

Pathogenesis of Bovine alphaherpesvirus 2 in calves following different routes of inoculation

Ganciclovir attenuates the respiratory disease induced by Equid alphaherpesvirus 1 in rabbits

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