Journal de virologie et de recherche antivirale

Phospholipase A2 Crotoxin B Isolated from the Venom of Crotalus durissus terrificus Exert Antiviral Effect against Dengue Virus and Yellow Fever Virus through Its Catalytic Activity

Raquel Rinaldi Russo, Vanessa Danielle Menjon M�ller, Adelia Cristina Oliveira Cintra, Luiz Tadeu Moraes Figueiredo, Suely Vilela Sampaio and Victor Hugo Aquino

Phospholipase A2 Crotoxin B Isolated from the Venom of Crotalus durissus terrificus Exert Antiviral Effect against Dengue Virus and Yellow Fever Virus through Its Catalytic Activity

Dengue virus and Yellow fever virus, which belong to the genus Flavivirus, family Flaviviridae, represent important arboviruses that cause diseases in humans. Although vaccine exists for Yellow fever virus, many cases of yellow fever are still reported in endemic regions of the Americas and, mainly, Africa. There is no therapeutic agent to treat infection with Dengue virus or Yellow fever virus; therefore, studies to identify drugs to combat these viruses are of great importance. Recently, we have found that phospholipase A₂ crotoxin subunit B and phospholipase A₂ “inter-cro” isolated from Crotalus durissus terrificus had an antiviral activity against Dengue virus serotype 2 and Yellow fever virus. However, Bothropstoxin-I, a PLA2-like isolated from Bothrops jararacussu, which has no phospholipase activity, showed no antiviral effect, suggesting that antiviral action was related to the enzymatic activity of phospholipases A₂. The aim of this study was to evaluate the role of the catalytic activity of the phospholipase A₂ crotoxin subunit B on the antiviral effect. The antiviral effect was abolished by the use of a chemically inhibited phospholipase A₂ crotoxin subunit B, a Ca⁺² (co-factor of the phospholipase) free medium or a Ca⁺²-chelating agent (Ethylenediaminetetraacetic acid) in the experiments. These results strongly suggest that phospholipases A₂ isolated from Crotalus durissus terrificus exert the antiviral effect by its enzymatic activity, cleaving glycerophospholipids on virus envelope and/or on the cell membrane.