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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 |
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creator | 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 |
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 |
format | article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-16130-w</identifier><identifier>PMID: 29162867</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Scientific reports, 2017-11, Vol.7 (1), p.1-8, Article 15931</ispartof><rights>The Author(s) 2017</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-faf7dd20f1f9b82c3f397b019f3a45512cbe5813582346e686978376dc176d963</citedby><cites>FETCH-LOGICAL-c517t-faf7dd20f1f9b82c3f397b019f3a45512cbe5813582346e686978376dc176d963</cites><orcidid>0000-0001-5525-9915 ; 0000-0003-4431-1380</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1967049571/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1967049571?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids></links><search><creatorcontrib>Chen, Ming</creatorcontrib><creatorcontrib>Aoki-Utsubo, Chie</creatorcontrib><creatorcontrib>Kameoka, Masanori</creatorcontrib><creatorcontrib>Deng, Lin</creatorcontrib><creatorcontrib>Terada, Yutaka</creatorcontrib><creatorcontrib>Kamitani, Wataru</creatorcontrib><creatorcontrib>Sato, Kei</creatorcontrib><creatorcontrib>Koyanagi, Yoshio</creatorcontrib><creatorcontrib>Hijikata, Makoto</creatorcontrib><creatorcontrib>Shindo, Keiko</creatorcontrib><creatorcontrib>Noda, Takeshi</creatorcontrib><creatorcontrib>Kohara, Michinori</creatorcontrib><creatorcontrib>Hotta, Hak</creatorcontrib><title>Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><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.</description><subject>13</subject><subject>13/106</subject><subject>631/326/596/1296</subject><subject>631/326/596/1413</subject><subject>631/326/596/1905</subject><subject>631/326/596/2148</subject><subject>Antiviral agents</subject><subject>Cytotoxicity</subject><subject>Dengue fever</subject><subject>Drug development</subject><subject>Encephalitis</subject><subject>Endoplasmic reticulum</subject><subject>Golgi apparatus</subject><subject>Hepatitis C</subject><subject>Herpes simplex</subject><subject>Humanities and Social Sciences</subject><subject>Influenza</subject><subject>Lipid bilayers</subject><subject>Lipids</subject><subject>Membranes</subject><subject>multidisciplinary</subject><subject>Phospholipase A2</subject><subject>Phospholipids</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Vector-borne diseases</subject><subject>Venom</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp1kctqFjEcxQdRbKl9AVcBN26m5jK5uRBqsSoUutF1yCT_fF_KzGRMZr7St_CRTTtFqtBALpDfOcnhNM1bgs8IZupD6QjXqsVEtkQQhtvbF80xxR1vKaP05ZPzUXNayg2ug1PdEf26OaKaCKqEPG5-f87J-rbM4Ja8jshOSzzEbAdkdzAt5SMq4DIs4NG8T6XOIc62ADqnaLF5B0tBGw_TAYY0A6pA9KiPg72DXJCHHA9VHnIa0bKHCvo0D7aM0aHqHN061IdHGPtsJ3jTvAp2KHD6uJ80Py-__Lj41l5df_1-cX7VOk7k0gYbpPcUBxJ0r6hjgWnZY6IDsx3nhLoeuCKMK8o6AUIJLRWTwjtSFy3YSfNp853XfgTvatiawsw5jjbfmWSj-fdminuzSwfDhVaduDd4_2iQ068VymLGWBwMQw2R1mKIFrITvCOyou_-Q2_Smqca74HCneaSVIpulMuplAzh72cINvedm61zUzs3D52b2ypim6hUeNpBfmL9vOoPvS-xlQ</recordid><startdate>20171121</startdate><enddate>20171121</enddate><creator>Chen, Ming</creator><creator>Aoki-Utsubo, Chie</creator><creator>Kameoka, 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envelope lipid bilayers derived from the endoplasmic reticulum membrane</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-faf7dd20f1f9b82c3f397b019f3a45512cbe5813582346e686978376dc176d963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13</topic><topic>13/106</topic><topic>631/326/596/1296</topic><topic>631/326/596/1413</topic><topic>631/326/596/1905</topic><topic>631/326/596/2148</topic><topic>Antiviral agents</topic><topic>Cytotoxicity</topic><topic>Dengue fever</topic><topic>Drug development</topic><topic>Encephalitis</topic><topic>Endoplasmic reticulum</topic><topic>Golgi apparatus</topic><topic>Hepatitis C</topic><topic>Herpes simplex</topic><topic>Humanities and Social Sciences</topic><topic>Influenza</topic><topic>Lipid bilayers</topic><topic>Lipids</topic><topic>Membranes</topic><topic>multidisciplinary</topic><topic>Phospholipase A2</topic><topic>Phospholipids</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Vector-borne diseases</topic><topic>Venom</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Ming</creatorcontrib><creatorcontrib>Aoki-Utsubo, Chie</creatorcontrib><creatorcontrib>Kameoka, Masanori</creatorcontrib><creatorcontrib>Deng, Lin</creatorcontrib><creatorcontrib>Terada, Yutaka</creatorcontrib><creatorcontrib>Kamitani, Wataru</creatorcontrib><creatorcontrib>Sato, Kei</creatorcontrib><creatorcontrib>Koyanagi, Yoshio</creatorcontrib><creatorcontrib>Hijikata, Makoto</creatorcontrib><creatorcontrib>Shindo, Keiko</creatorcontrib><creatorcontrib>Noda, Takeshi</creatorcontrib><creatorcontrib>Kohara, 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Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Ming</au><au>Aoki-Utsubo, Chie</au><au>Kameoka, Masanori</au><au>Deng, Lin</au><au>Terada, Yutaka</au><au>Kamitani, Wataru</au><au>Sato, Kei</au><au>Koyanagi, Yoshio</au><au>Hijikata, Makoto</au><au>Shindo, Keiko</au><au>Noda, Takeshi</au><au>Kohara, Michinori</au><au>Hotta, Hak</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><date>2017-11-21</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>1</spage><epage>8</epage><pages>1-8</pages><artnum>15931</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29162867</pmid><doi>10.1038/s41598-017-16130-w</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5525-9915</orcidid><orcidid>https://orcid.org/0000-0003-4431-1380</orcidid><oa>free_for_read</oa></addata></record> |
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source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
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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