Resumo

Poliovirus (PV) the causal agent of poliomyelitis remains endemic in some countries in Africa and Asia. The bovine herpesvirus-1 (BoHV-1) is the causal agent of rhinotracheitis, balanoposthitis and fatal systemic infections. The herpes simplex virus (HSV) causes benign infections, but, can be severe in immunocompromised. Besides the veterinarian and medical importance, these viruses are used as models of RNA and DNA virus for many in vitro studies. The inhibitory effects of natural compounds in the replication of virus, including drug-resistant strains are reported. The Azadirachta indica, popularly known as neem, is widely used in Indian ayurvedic and homeopathic medicine for treatment of several diseases, including viral infections. We evaluated the antiviral activity of A. indica, leaves polysaccharides (P1 and P2) and their sulfated derivatives (P1S and P2S), in PV, BoHV-1 and HSV-1 infection, in HEp-2 cells. The antiviral activity was determined by plaques reduction assay (PRA) and the inhibition of viral protein synthesis confirmed by immunofluorescence (IF). The compounds showed no HEp-2 cells toxicity up 1mg/ml by MTT assay. The 50% inhibitory concentration (IC50)/selectivity index (SI) determined for PV, were 80μg.ml^-1/18; 37.5μg.ml^-1/42.6; 77.5μg.ml^-1/20.6; 12.1μg.ml^-1/131.9 for P1, P1S, P2 and P2S, respectively. For HSV-1 and BoHV-1, the compounds showed similar inhibition with IC50/SI of approximately 100μg.ml^-1/14.4 (for P1) and 30μg.ml^-1/50 (for P1S). P2 showed no effect and P2S inhibited HSV-1 only (80.5μg.ml^-1/16.8. These values were approximately similar for all tested virus. The compounds presented a better antiviral effect when added simultaneously with the virus (time zero) probably due to different mechanisms of action (virucidal and inhibition of adsorption and penetration effects) at this time period. The viral protein synthesis inhibition were dose-dependent for all the strains. In addition, the anti-HSV-1 activity for all polysaccharides inhibited viral DNA synthesis. It is demonstrated that A. indica polysaccharides are appropriate for the antiviral study (RNA/DNA) and their effects may occur in several stages of viral replication.