Evaluation of the antiviral activities of Bacharis dracunculifolia and quercetin on Equid herpesvirus 1 in a murine model.

Equid herpesvirus 1 (EHV-1) is a pathogen of high economic importance in equine breeding operations around the world. EHV-1 infection causes respiratory, neurologic and reproductive disease. The absence of an efficient therapy has caught the attention of the scientific community and the therapeutic activities of natural products with its antivirals effects might be effective for the disease's treatment. Herein it was evaluated the prophylactic and therapeutic potential of quercetin and ethanolic extracts of Bacharis dracunculifolia formulations compared to Penciclovir® in an in vivo EHV-1 infection model. Six to seven-week-old female C57BL/6 mice were randomly organized into fifteen groups with six animals each. Ex-1 represents the treatment post-challenge groups to assess morbidity, mortality and weight variation. Ex-2 represents the animals that received treatment for 5 days post-challenge for lesion evaluation. In Ex-3 animals were treated prior to viral challenge to assess morbidity, mortality and weight variation. All mice in the treatment groups were challenged by intranasal inoculation of 3.0 × 105 TCID50 EHV-1. The quercetin and B. dracunculifolia treatment decreased morbimortality in post-challenge treatment (Ex-1) and EHV-1 related lesions (Ex-2). Treatment prior to viral challenge (Ex-3) did not show any significant results. Based on the results of the present study, both tested formulations are promising antiviral agents for the treatment of EHV-1 infection.

The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication.

Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of disease caused by the virus. ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analogue derived from the prodrug azathioprine, against the epidemic ZIKV strain circulating in Brazil. In all of the assays, an epithelial (Vero) and a human neuronal (SH-SY5Y) cell line were used to evaluate the cytotoxicity and effective concentrations of 6MMPr against ZIKV. Levels of ZIKV-RNA, viral infectious titre and the percentage of infected cells in the presence or absence of 6MMPr were used to determine antiviral efficacy. 6MMPr decreased ZIKV production by >99% in both cell lines in a dose- and time-dependent manner. Interestingly, 6MMPr was 1.6 times less toxic to SH-SY5Y cells compared with Vero cells, presenting a 50% cytotoxic concentrations (CC50) of 460.3 µM and 291 µM, respectively. The selectivity index of 6MMPr for Vero and SH-SY5Y cells was 11.9 and 22.7, respectively, highlighting the safety profile of the drug to neuronal cells. Taken together, these results identify, for the first time, the thiopurine nucleoside analogue 6MMPr as a promising antiviral candidate against ZIKV that warrants further in vivo evaluation.

6-methylmercaptopurine riboside, a thiopurine nucleoside with antiviral activity against canine distemper virus in vitro.

BACKGROUND: Canine distemper (CD) is a widespread infectious disease that can severely impact a variety of species in the order Carnivora, as well as non-carnivore species such as non-human primates. Despite large-scale vaccination campaigns, several fatal outbreaks have been reported in wild and domestic carnivore populations. This, in association with expansion of the disease host range and the development of vaccine-escape strains, has contributed to an increased demand for therapeutic strategies synergizing with vaccine programs for effectively controlling canine distemper. 6-methylmercaptopurine riboside (6MMPr) is a modified thiopurine nucleoside with known antiviral properties against certain RNA viruses. METHODS: We tested the inhibitory effects of 6MMPr against a wild-type CDV strain infection in cell culture. We measured infectious particle production and viral RNA levels in treated and untreated CDV-infected cells. Ribavirin (RIB) was used as a positive control. RESULTS: Here, we report for the first time the antiviral effects of 6MMPr against canine distemper virus (CDV) in vitro. 6MMPr was able to reduce viral RNA levels and to inhibit the production of infectious CDV particles. The therapeutic selectivity of 6MMPr was approximately six times higher than that of ribavirin. CONCLUSION: Our results indicate that 6MMPr has high anti-CDV potential and warrants further testing against other paramyxoviruses, as well as clinical testing of the compound against CDV.