Evaluation of antiviral activity of phenolic compounds and derivatives against rabies virus.

Human rabies is a viral disease with a great impact on public health, mainly on account of its fatal course in the majority of cases. Despite the well-established prophylaxis by immunization, rabies is believed to be responsible for 40,000-70,000 human deaths per year, mostly in endemic areas. Palliative support and experimental protocols to avoid death have been employed with no expressive results, with the exception of a recent human case of recovery from rabies. No antiviral drugs are currently available to fight against this infection. In combination with the prophylaxis, an antiviral drug would be useful for human rabies treatment, providing enhanced protection against the encephalitis caused by the virus. Phenolic compounds are derived from the secondary plant metabolism, although they can also be obtained by synthetic processes. Many studies have shown a great range of pharmacological effects for these substances, including vasodilatation, antiallergenic, antiinflammatory and antiviral properties, among others. In this study, the potential in-vitro anti-rabies activity of 24 synthetic phenolic compounds was evaluated using McCoy cells and PV rabies strain. The cytotoxicity (CC50) was assayed by the MTT method and the antiviral activity (IC50) was estimated by the inhibition of viral cytopathic effects. Isoprinosine and ketamine were used as positive controls. The tested compounds showed selectivity indices (SI=CC50/IC50) ranging from 1.0 to 3.9. Six phenolic compounds failed to inhibit the cytopathic effect to any degree, and four showed SI > or = 3.0. According to these results, some probable structure-activity relationships are suggested. It was observed that the presence of free hydroxyl and ether groups influenced the anti-rabies activity. However, additional studies are required to establish these relationships.

Influence of the CCR-5/MIP-1 α axis in the pathogenesis of Rocio virus encephalitis in a mouse model.

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5-/- mice, while MIP-1 α-/- mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.

Evaluation of antiviral activity of South American plant extracts against herpes simplex virus type 1 and rabies virus.

This paper describes the screening of different South American plant extracts and fractions. Aqueous and organic extracts were prepared and tested for antiherpetic (HSV-1, KOS and 29R strains) and antirabies (PV strain) activities. The evaluation of the potential antiviral activity of these extracts was performed by using an MTT assay for HSV-1, and by a viral cytopathic effect (CPE) inhibitory method for rabies virus (RV). The results were expressed as 50% cytotoxicity (CC(50)) for MTT assay and 50% effective (EC(50)) concentrations for CPE, and with them it was possible to calculate the selectivity indices (SI = CC(50)/EC(50)) of each tested material. From the 18 extracts/fractions tested, six extracts and four fractions showed antiviral action. Ilex paraguariensis, Lafoensia pacari, Passiflora edulis, Rubus imperialis and Slonea guianensis showed values of SI > 7 against HSV-1 KOS and 29-R strains and Alamanda schottii showed a SI of 5.6 against RV, PV strain.