Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7
Identifieur interne : 001D88 ( Main/Merge ); précédent : 001D87; suivant : 001D89Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7
Auteurs : Yaoqing Chen [République populaire de Chine] ; Luyang Cao [République populaire de Chine] ; Maohua Zhong [République populaire de Chine] ; Yan Zhang [République populaire de Chine] ; Chen Han [République populaire de Chine] ; Qiaoli Li [République populaire de Chine] ; Jingyi Yang [République populaire de Chine] ; Dihan Zhou [République populaire de Chine] ; Wei Shi [République populaire de Chine] ; Benxia He [République populaire de Chine] ; Fang Liu [République populaire de Chine] ; Jie Yu [République populaire de Chine] ; Ying Sun [République populaire de Chine] ; Yuan Cao [République populaire de Chine] ; Yaoming Li [République populaire de Chine] ; Wenxin Li [République populaire de Chine] ; Deying Guo [République populaire de Chine] ; Zhijian Cao [République populaire de Chine] ; Huimin Yan [République populaire de Chine]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Descripteurs français
- KwdFr :
- Agents antiVIH (pharmacologie), Agents antiVIH (synthèse chimique), Agents antiVIH (toxicité), Conception de médicament, Données de séquences moléculaires, Humains, Liaison aux protéines, Lignée cellulaire, Peptides antimicrobiens cationiques (pharmacologie), Peptides antimicrobiens cationiques (synthèse chimique), Peptides antimicrobiens cationiques (toxicité), Relation dose-effet des médicaments, Structure secondaire des protéines, Séquence d'acides aminés, VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), Venins de scorpion (pharmacologie), Venins de scorpion (synthèse chimique), Venins de scorpion (toxicité).
- MESH :
- pharmacologie : Agents antiVIH, Peptides antimicrobiens cationiques, Venins de scorpion.
- synthèse chimique : Agents antiVIH, Peptides antimicrobiens cationiques, Venins de scorpion.
- toxicité : Agents antiVIH, Peptides antimicrobiens cationiques, Venins de scorpion.
- Conception de médicament, Données de séquences moléculaires, Humains, Liaison aux protéines, Lignée cellulaire, Relation dose-effet des médicaments, Structure secondaire des protéines, Séquence d'acides aminés, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Amino Acid Sequence, Anti-HIV Agents (chemical synthesis), Anti-HIV Agents (pharmacology), Anti-HIV Agents (toxicity), Antimicrobial Cationic Peptides (chemical synthesis), Antimicrobial Cationic Peptides (pharmacology), Antimicrobial Cationic Peptides (toxicity), Cell Line, Dose-Response Relationship, Drug, Drug Design, HIV-1 (drug effects), Humans, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Scorpion Venoms (chemical synthesis), Scorpion Venoms (pharmacology), Scorpion Venoms (toxicity).
- MESH :
- chemical , chemical synthesis : Anti-HIV Agents, Antimicrobial Cationic Peptides, Scorpion Venoms.
- chemical , pharmacology : Anti-HIV Agents, Antimicrobial Cationic Peptides, Scorpion Venoms.
- chemical , toxicity : Anti-HIV Agents, Antimicrobial Cationic Peptides, Scorpion Venoms.
- drug effects : HIV-1.
- Amino Acid Sequence, Cell Line, Dose-Response Relationship, Drug, Drug Design, Humans, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary.
Abstract
For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.
Url:
DOI: 10.1371/journal.pone.0034947
PubMed: 22536342
PubMed Central: 3334916
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PMC:3334916Le document en format XML
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<author><name sortKey="Zhong, Maohua" sort="Zhong, Maohua" uniqKey="Zhong M" first="Maohua" last="Zhong">Maohua Zhong</name>
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<author><name sortKey="Zhang, Yan" sort="Zhang, Yan" uniqKey="Zhang Y" first="Yan" last="Zhang">Yan Zhang</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<placeName><settlement type="city">Wuhan</settlement>
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</placeName>
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<author><name sortKey="Zhou, Dihan" sort="Zhou, Dihan" uniqKey="Zhou D" first="Dihan" last="Zhou">Dihan Zhou</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Wei" sort="Shi, Wei" uniqKey="Shi W" first="Wei" last="Shi">Wei Shi</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="He, Benxia" sort="He, Benxia" uniqKey="He B" first="Benxia" last="He">Benxia He</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Liu, Fang" sort="Liu, Fang" uniqKey="Liu F" first="Fang" last="Liu">Fang Liu</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yu, Jie" sort="Yu, Jie" uniqKey="Yu J" first="Jie" last="Yu">Jie Yu</name>
<affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sun, Ying" sort="Sun, Ying" uniqKey="Sun Y" first="Ying" last="Sun">Ying Sun</name>
<affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cao, Yuan" sort="Cao, Yuan" uniqKey="Cao Y" first="Yuan" last="Cao">Yuan Cao</name>
<affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Yaoming" sort="Li, Yaoming" uniqKey="Li Y" first="Yaoming" last="Li">Yaoming Li</name>
<affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Wenxin" sort="Li, Wenxin" uniqKey="Li W" first="Wenxin" last="Li">Wenxin Li</name>
<affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
<orgName type="university">Université de Wuhan</orgName>
</affiliation>
</author>
<author><name sortKey="Guo, Deying" sort="Guo, Deying" uniqKey="Guo D" first="Deying" last="Guo">Deying Guo</name>
<affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
<orgName type="university">Université de Wuhan</orgName>
</affiliation>
</author>
<author><name sortKey="Cao, Zhijian" sort="Cao, Zhijian" uniqKey="Cao Z" first="Zhijian" last="Cao">Zhijian Cao</name>
<affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
<orgName type="university">Université de Wuhan</orgName>
</affiliation>
</author>
<author><name sortKey="Yan, Huimin" sort="Yan, Huimin" uniqKey="Yan H" first="Huimin" last="Yan">Huimin Yan</name>
<affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
<orgName type="university">Université de Wuhan</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2012">2012</date>
</imprint>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Anti-HIV Agents (chemical synthesis)</term>
<term>Anti-HIV Agents (pharmacology)</term>
<term>Anti-HIV Agents (toxicity)</term>
<term>Antimicrobial Cationic Peptides (chemical synthesis)</term>
<term>Antimicrobial Cationic Peptides (pharmacology)</term>
<term>Antimicrobial Cationic Peptides (toxicity)</term>
<term>Cell Line</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Design</term>
<term>HIV-1 (drug effects)</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>Protein Binding</term>
<term>Protein Structure, Secondary</term>
<term>Scorpion Venoms (chemical synthesis)</term>
<term>Scorpion Venoms (pharmacology)</term>
<term>Scorpion Venoms (toxicity)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Agents antiVIH (pharmacologie)</term>
<term>Agents antiVIH (synthèse chimique)</term>
<term>Agents antiVIH (toxicité)</term>
<term>Conception de médicament</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Peptides antimicrobiens cationiques (pharmacologie)</term>
<term>Peptides antimicrobiens cationiques (synthèse chimique)</term>
<term>Peptides antimicrobiens cationiques (toxicité)</term>
<term>Relation dose-effet des médicaments</term>
<term>Structure secondaire des protéines</term>
<term>Séquence d'acides aminés</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term>
<term>Venins de scorpion (pharmacologie)</term>
<term>Venins de scorpion (synthèse chimique)</term>
<term>Venins de scorpion (toxicité)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Anti-HIV Agents</term>
<term>Antimicrobial Cationic Peptides</term>
<term>Scorpion Venoms</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-HIV Agents</term>
<term>Antimicrobial Cationic Peptides</term>
<term>Scorpion Venoms</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Anti-HIV Agents</term>
<term>Antimicrobial Cationic Peptides</term>
<term>Scorpion Venoms</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Agents antiVIH</term>
<term>Peptides antimicrobiens cationiques</term>
<term>Venins de scorpion</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Agents antiVIH</term>
<term>Peptides antimicrobiens cationiques</term>
<term>Venins de scorpion</term>
</keywords>
<keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Agents antiVIH</term>
<term>Peptides antimicrobiens cationiques</term>
<term>Venins de scorpion</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Cell Line</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Design</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>Protein Binding</term>
<term>Protein Structure, Secondary</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Conception de médicament</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Relation dose-effet des médicaments</term>
<term>Structure secondaire des protéines</term>
<term>Séquence d'acides aminés</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
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<front><div type="abstract" xml:lang="en"><p>For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC<sub>50</sub>
value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.</p>
</div>
</front>
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