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

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...

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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
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description 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.
doi_str_mv 10.1038/s41598-017-16130-w
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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
title Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane
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