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Hepatitis C virus (HCV), dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the family  Flaviviridae . Their viral particles have the envelope composed of viral proteins and a lipid bilayer acquired from budding through the endoplasmic reticulum (ER). The phospholipid content of the ER membrane differs from that of the plasma membrane (PM). The phospholipase A 2  (PLA 2 ) superfamily consists of a large number of members that specifically catalyse the hydrolysis of phospholipids at a particular position. Here we show that the CM-II isoform of secreted PLA 2  obtained from  Naja mossambica mossambica  snake venom (CM-II-sPLA 2 ) possesses potent virucidal (neutralising) activity against HCV, DENV and JEV, with 50% inhibitory concentrations (IC 50 ) of 0.036, 0.31 and 1.34 ng/ml, respectively. In contrast, the IC 50  values of CM-II-sPLA 2  against viruses that bud through the PM (Sindbis virus, influenza virus and Sendai virus) or  trans -Golgi network (TGN) (herpes simplex virus) were >10,000 ng/ml. Moreover, the 50% cytotoxic (CC 50 ) and haemolytic (HC 50 ) concentrations of CM-II-sPLA 2  were >10,000 ng/ml, implying that CM-II-sPLA 2  did not significantly damage the PM. These results suggest that CM-II-sPLA 2  and its derivatives are good candidates for the development of broad-spectrum antiviral drugs that target viral envelope lipid bilayers derived from the ER membrane.

Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane