Broad-spectrum antiviral agents: secreted phospholipase A 2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane

• Published in: Scientific reports Vol. 7; no. 1; p. 15931
• Main Authors: Chen, Ming, Aoki-Utsubo, Chie, Kameoka, Masanori, Deng, Lin, Terada, Yutaka, Kamitani, Wataru, Sato, Kei, Koyanagi, Yoshio, Hijikata, Makoto, Shindo, Keiko, Noda, Takeshi, Kohara, Michinori, Hotta, Hak
• Format: Journal Article
• Language: English
• Published: England 21.11.2017
• Subjects: Animals; Antiviral Agents - pharmacology; Cattle; Cell Death - drug effects; Cell Membrane - drug effects; Cell Membrane - metabolism; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Hemolysis - drug effects; Humans; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; Isoenzymes - metabolism; Lipid Bilayers - metabolism; Membrane Lipids - metabolism; Phospholipases A2, Secretory - pharmacology; Swine; Terpenes - pharmacology; Virus Internalization - drug effects; Virus Replication - drug effects; Viruses - drug effects
• ISSN: 2045-2322

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 (PLA ) 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 obtained from Naja mossambica mossambica snake venom (CM-II-sPLA ) possesses potent virucidal (neutralising) activity against HCV, DENV and JEV, with 50% inhibitory concentrations (IC ) of 0.036, 0.31 and 1.34 ng/ml, respectively. In contrast, the IC values of CM-II-sPLA 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 ) and haemolytic (HC ) concentrations of CM-II-sPLA were >10,000 ng/ml, implying that CM-II-sPLA did not significantly damage the PM. These results suggest that CM-II-sPLA 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.