Novel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus.
Identifieur interne : 000445 ( Main/Exploration ); précédent : 000444; suivant : 000446Novel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus.
Auteurs : Xinyu Huang [République populaire de Chine] ; Meng Li [République populaire de Chine] ; Yurui Xu [République populaire de Chine] ; Jikang Zhang [République populaire de Chine] ; Xia Meng [République populaire de Chine] ; Xueying An [République populaire de Chine] ; Lei Sun [République populaire de Chine] ; Leilei Guo [République populaire de Chine] ; Xue Shan [République populaire de Chine] ; Junliang Ge [République populaire de Chine] ; Jiao Chen [République populaire de Chine] ; Yadong Luo [République populaire de Chine] ; Heming Wu [République populaire de Chine] ; Yu Zhang [République populaire de Chine] ; Qing Jiang [République populaire de Chine] ; Xinghai Ning [République populaire de Chine]Source :
- ACS applied materials & interfaces [ 1944-8252 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (), Antiviraux (pharmacologie), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Dichroïsme circulaire, Femelle, Humains, Lignée cellulaire, Nanotubes (), Or (), Peptides (), Peptides (pharmacologie), Souris, Structure secondaire des protéines.
- MESH :
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- pharmacologie : Antiviraux, Peptides.
- Animaux, Antiviraux, Coronavirus du syndrome respiratoire du Moyen-Orient, Dichroïsme circulaire, Femelle, Humains, Lignée cellulaire, Nanotubes, Or, Peptides, Souris, Structure secondaire des protéines.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Cell Line, Circular Dichroism, Female, Gold (chemistry), Humans, Mice, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Nanotubes (chemistry), Peptides (chemistry), Peptides (pharmacology), Protein Structure, Secondary.
- MESH :
- chemical , chemistry : Antiviral Agents, Gold, Peptides.
- chemical , pharmacology : Antiviral Agents, Peptides.
- chemistry : Nanotubes.
- drug effects : Middle East Respiratory Syndrome Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- Animals, Cell Line, Circular Dichroism, Female, Humans, Mice, Protein Structure, Secondary.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. Currently, only few antiviral agents are available for the treatment of MERS, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. Therefore, the development of effective treatment for MERS is urgently needed. In this study, a series of heptad repeat 1 (HR1) peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections. Particularly, peptide pregnancy-induced hypertension (PIH) exhibits potent inhibitory activity with IC50 of 1.171 μM, and its inhibitory effects can be further increased to 10-fold by forming a gold nanorod complex (PIH-AuNRs). In addition, PIH-AuNRs display enhanced metabolic stability and biocompatibility in vitro and in vivo and, therefore, effectively prevent MERS-CoV-associated membrane fusion. In summary, PIH-AuNRs represent a novel class of antiviral agents and have a great potential in treating MERS in the clinic.
DOI: 10.1021/acsami.9b04240
PubMed: 31099550
Affiliations:
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Le document en format XML
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wicri:level="1"><nlm:affiliation>Jiangsu Key Laboratory of Oral Diseases , Nanjing Medical University , Nanjing 210029 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jiangsu Key Laboratory of Oral Diseases , Nanjing Medical University , Nanjing 210029 </wicri:regionArea><wicri:noRegion>Nanjing 210029 </wicri:noRegion></affiliation></author><author><name sortKey="Xu, Yurui" sort="Xu, Yurui" uniqKey="Xu Y" first="Yurui" last="Xu">Yurui Xu</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Jikang" sort="Zhang, Jikang" uniqKey="Zhang J" first="Jikang" last="Zhang">Jikang Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author><author><name sortKey="Meng, Xia" sort="Meng, Xia" uniqKey="Meng X" first="Xia" last="Meng">Xia Meng</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author><author><name sortKey="An, Xueying" sort="An, Xueying" uniqKey="An X" first="Xueying" last="An">Xueying An</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital , The Affiliated Hospital of Nanjing University Medical School , Nanjing 210008 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital , The Affiliated Hospital of Nanjing University Medical School , Nanjing 210008 </wicri:regionArea><wicri:noRegion>Nanjing 210008 </wicri:noRegion></affiliation></author><author><name sortKey="Sun, Lei" sort="Sun, Lei" uniqKey="Sun L" first="Lei" last="Sun">Lei Sun</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author><author><name sortKey="Guo, Leilei" sort="Guo, Leilei" uniqKey="Guo L" first="Leilei" last="Guo">Leilei Guo</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing 210009 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing 210009 </wicri:regionArea><wicri:noRegion>Nanjing 210009 </wicri:noRegion></affiliation></author><author><name sortKey="Shan, Xue" sort="Shan, Xue" uniqKey="Shan X" first="Xue" last="Shan">Xue Shan</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author><author><name sortKey="Ge, Junliang" sort="Ge, Junliang" uniqKey="Ge J" first="Junliang" last="Ge">Junliang Ge</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author><author><name sortKey="Chen, Jiao" sort="Chen, Jiao" uniqKey="Chen J" first="Jiao" last="Chen">Jiao Chen</name><affiliation wicri:level="1"><nlm:affiliation>Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028 </wicri:regionArea><wicri:noRegion>Nanjing 210028 </wicri:noRegion></affiliation></author><author><name sortKey="Luo, Yadong" sort="Luo, Yadong" uniqKey="Luo Y" first="Yadong" last="Luo">Yadong Luo</name><affiliation wicri:level="1"><nlm:affiliation>Jiangsu Key Laboratory of Oral Diseases , Nanjing Medical University , Nanjing 210029 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jiangsu Key Laboratory of Oral Diseases , Nanjing Medical University , Nanjing 210029 </wicri:regionArea><wicri:noRegion>Nanjing 210029 </wicri:noRegion></affiliation></author><author><name sortKey="Wu, Heming" sort="Wu, Heming" uniqKey="Wu H" first="Heming" last="Wu">Heming Wu</name><affiliation wicri:level="1"><nlm:affiliation>Jiangsu Key Laboratory of Oral Diseases , Nanjing Medical University , Nanjing 210029 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jiangsu Key Laboratory of Oral Diseases , Nanjing Medical University , Nanjing 210029 </wicri:regionArea><wicri:noRegion>Nanjing 210029 </wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Qing" sort="Jiang, Qing" uniqKey="Jiang Q" first="Qing" last="Jiang">Qing Jiang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital , The Affiliated Hospital of Nanjing University Medical School , Nanjing 210008 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital , The Affiliated Hospital of Nanjing University Medical School , Nanjing 210008 </wicri:regionArea><wicri:noRegion>Nanjing 210008 </wicri:noRegion></affiliation></author><author><name sortKey="Ning, Xinghai" sort="Ning, Xinghai" uniqKey="Ning X" first="Xinghai" last="Ning">Xinghai Ning</name><affiliation wicri:level="1"><nlm:affiliation>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing National Laboratory of Microstructures, College of Engineering and Applied Sciences , Nanjing University , Nanjing 210093 </wicri:regionArea><wicri:noRegion>Nanjing 210093 </wicri:noRegion></affiliation></author></analytic><series><title level="j">ACS applied materials & interfaces</title><idno type="eISSN">1944-8252</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (chemistry)</term><term>Antiviral Agents (pharmacology)</term><term>Cell Line</term><term>Circular Dichroism</term><term>Female</term><term>Gold (chemistry)</term><term>Humans</term><term>Mice</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Nanotubes (chemistry)</term><term>Peptides (chemistry)</term><term>Peptides (pharmacology)</term><term>Protein Structure, Secondary</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux ()</term><term>Antiviraux (pharmacologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term><term>Dichroïsme circulaire</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire</term><term>Nanotubes ()</term><term>Or ()</term><term>Peptides ()</term><term>Peptides (pharmacologie)</term><term>Souris</term><term>Structure secondaire des protéines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Gold</term><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Nanotubes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Peptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Circular Dichroism</term><term>Female</term><term>Humans</term><term>Mice</term><term>Protein Structure, Secondary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antiviraux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Dichroïsme circulaire</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire</term><term>Nanotubes</term><term>Or</term><term>Peptides</term><term>Souris</term><term>Structure secondaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. Currently, only few antiviral agents are available for the treatment of MERS, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. Therefore, the development of effective treatment for MERS is urgently needed. In this study, a series of heptad repeat 1 (HR1) peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections. Particularly, peptide pregnancy-induced hypertension (PIH) exhibits potent inhibitory activity with IC<sub>50</sub> of 1.171 μM, and its inhibitory effects can be further increased to 10-fold by forming a gold nanorod complex (PIH-AuNRs). In addition, PIH-AuNRs display enhanced metabolic stability and biocompatibility in vitro and in vivo and, therefore, effectively prevent MERS-CoV-associated membrane fusion. In summary, PIH-AuNRs represent a novel class of antiviral agents and have a great potential in treating MERS in the clinic.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Huang, Xinyu" sort="Huang, Xinyu" uniqKey="Huang X" first="Xinyu" last="Huang">Xinyu Huang</name></noRegion><name sortKey="An, Xueying" sort="An, Xueying" uniqKey="An X" first="Xueying" last="An">Xueying An</name><name sortKey="Chen, Jiao" sort="Chen, Jiao" uniqKey="Chen J" first="Jiao" last="Chen">Jiao Chen</name><name sortKey="Ge, Junliang" sort="Ge, Junliang" uniqKey="Ge J" first="Junliang" last="Ge">Junliang Ge</name><name sortKey="Guo, Leilei" sort="Guo, Leilei" uniqKey="Guo L" first="Leilei" last="Guo">Leilei Guo</name><name sortKey="Jiang, Qing" sort="Jiang, Qing" uniqKey="Jiang Q" first="Qing" last="Jiang">Qing Jiang</name><name sortKey="Li, Meng" sort="Li, Meng" uniqKey="Li M" first="Meng" last="Li">Meng Li</name><name sortKey="Luo, Yadong" sort="Luo, Yadong" uniqKey="Luo Y" first="Yadong" last="Luo">Yadong Luo</name><name sortKey="Meng, Xia" sort="Meng, Xia" uniqKey="Meng X" first="Xia" last="Meng">Xia Meng</name><name sortKey="Ning, Xinghai" sort="Ning, Xinghai" uniqKey="Ning X" first="Xinghai" last="Ning">Xinghai Ning</name><name sortKey="Shan, Xue" sort="Shan, Xue" uniqKey="Shan X" first="Xue" last="Shan">Xue Shan</name><name sortKey="Sun, Lei" sort="Sun, Lei" uniqKey="Sun L" first="Lei" last="Sun">Lei Sun</name><name sortKey="Wu, Heming" sort="Wu, Heming" uniqKey="Wu H" first="Heming" last="Wu">Heming Wu</name><name sortKey="Xu, Yurui" sort="Xu, Yurui" uniqKey="Xu Y" first="Yurui" last="Xu">Yurui Xu</name><name sortKey="Zhang, Jikang" sort="Zhang, Jikang" uniqKey="Zhang J" first="Jikang" last="Zhang">Jikang Zhang</name><name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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