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

• Published in: Scientific reports 2017-11, Vol.7 (1), p.1-8, Article 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: Article
• Language: English
• Subjects: 13; 13/106; 631/326/596/1296; 631/326/596/1413; 631/326/596/1905; 631/326/596/2148; Antiviral agents; Cytotoxicity; Dengue fever; Drug development; Encephalitis; Endoplasmic reticulum; Golgi apparatus; Hepatitis C; Herpes simplex; Humanities and Social Sciences; Influenza; Lipid bilayers; Lipids; Membranes; multidisciplinary; Phospholipase A2; Phospholipids; Science; Science (multidisciplinary); Vector-borne diseases; Venom
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-16130-w

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.