Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship
Objectives To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3 pro ) expressed in Escherichia coli BL21 (DE3) and their structure activity relationship. Results ZIKV NS2B-NS3 pro was expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a...
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| Veröffentlicht in: | Biotechnology letters 2017-03, Vol.39 (3), p.415-421 |
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| creator | Lim, Hee-jung Nguyen, Thi Thanh Hanh Kim, Nahyun M. Park, Jun-Seong Jang, Tae-Su Kim, Doman |
| description | Objectives
To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3
pro
) expressed in
Escherichia coli
BL21 (DE3) and their structure activity relationship.
Results
ZIKV NS2B-NS3
pro
was expressed in
E. coli
BL21(DE3) as a 35 kDa protein. It had a
K
m
of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3
pro
was used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3
pro
by 6.2–88%. Seven polyphenol compounds had IC
50
ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3
pro
protease. Its IC
50
value was 22 ± 0.2 µM with a
K
i
value of 8.9 ± 1.9 µM.
Conclusion
The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3
pro
can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3
pro
. |
| doi_str_mv | 10.1007/s10529-016-2261-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7088272</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1868327869</sourcerecordid><originalsourceid>FETCH-LOGICAL-c573t-78c66a8a95e9dac298e8763a3474980956b544bdd5932ea631a2e3d8971ae8413</originalsourceid><addsrcrecordid>eNqNkktrGzEUhUVpady0P6CbIuimm2n1GL02hST0YRKSRdpNN0KeuWMrjCVH0hj87yvjNKSBQFZa3O-eyzk6CL2n5DMlRH3JlAhmGkJlw5ikjXyBZlQo3kil5Es0I7SljWgNO0Jvcr4hhBhF1Gt0xJTWQhAzQ7fzsPILX2LaYRgG6AqOAx5Gt40h-j5jt3Q-5IIvr9lpc3nN8SbFAi7DnvszPz_BW5-myoUelxX4hHNJU1emBNh1xW992eEEoys-hrzym7fo1eDGDO_u3mP0-_u3X2c_m4urH_Ozk4umqw5Ko3QnpdPOCDC965jRoJXkjreqNZoYIReibRd9Lwxn4CSnjgHvtVHUgW4pP0ZfD7qbabGGvoNQkhvtJvm1Szsbnbf_T4Jf2WXcWkW0ZopVgU93AineTpCLXfvcwTi6AHHKlup6hipO6DNQqXkNXZpnoG1LWDXJK_rxEXoTpxRqaHtBwWT9dF0peqC6FHNOMNxbpMTua2IPNbG1JnZfEyvrzoeH2dxv_OtFBdgByHUUlpAenH5S9S8gKce9</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1865262268</pqid></control><display><type>article</type><title>Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Lim, Hee-jung ; Nguyen, Thi Thanh Hanh ; Kim, Nahyun M. ; Park, Jun-Seong ; Jang, Tae-Su ; Kim, Doman</creator><creatorcontrib>Lim, Hee-jung ; Nguyen, Thi Thanh Hanh ; Kim, Nahyun M. ; Park, Jun-Seong ; Jang, Tae-Su ; Kim, Doman</creatorcontrib><description>Objectives
To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3
pro
) expressed in
Escherichia coli
BL21 (DE3) and their structure activity relationship.
Results
ZIKV NS2B-NS3
pro
was expressed in
E. coli
BL21(DE3) as a 35 kDa protein. It had a
K
m
of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3
pro
was used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3
pro
by 6.2–88%. Seven polyphenol compounds had IC
50
ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3
pro
protease. Its IC
50
value was 22 ± 0.2 µM with a
K
i
value of 8.9 ± 1.9 µM.
Conclusion
The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3
pro
can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3
pro
.</description><identifier>ISSN: 0141-5492</identifier><identifier>EISSN: 1573-6776</identifier><identifier>DOI: 10.1007/s10529-016-2261-6</identifier><identifier>PMID: 27885509</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Applied Microbiology ; Biochemistry ; Biomedical and Life Sciences ; Biotechnology ; E coli ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; Flavonoids ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Inhibition ; Life Sciences ; Microbiology ; Original Research Paper ; Polyphenols ; Polyphenols - chemistry ; Polyphenols - pharmacology ; Protease ; Protease Inhibitors - chemistry ; Protease Inhibitors - pharmacology ; Proteases ; Proteins ; Structure-Activity Relationship ; Vector-borne diseases ; Viral Nonstructural Proteins - antagonists & inhibitors ; Viral Nonstructural Proteins - metabolism ; Viruses ; Zika virus ; Zika Virus - enzymology</subject><ispartof>Biotechnology letters, 2017-03, Vol.39 (3), p.415-421</ispartof><rights>Springer Science+Business Media Dordrecht 2016</rights><rights>Biotechnology Letters is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-78c66a8a95e9dac298e8763a3474980956b544bdd5932ea631a2e3d8971ae8413</citedby><cites>FETCH-LOGICAL-c573t-78c66a8a95e9dac298e8763a3474980956b544bdd5932ea631a2e3d8971ae8413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10529-016-2261-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10529-016-2261-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27885509$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lim, Hee-jung</creatorcontrib><creatorcontrib>Nguyen, Thi Thanh Hanh</creatorcontrib><creatorcontrib>Kim, Nahyun M.</creatorcontrib><creatorcontrib>Park, Jun-Seong</creatorcontrib><creatorcontrib>Jang, Tae-Su</creatorcontrib><creatorcontrib>Kim, Doman</creatorcontrib><title>Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship</title><title>Biotechnology letters</title><addtitle>Biotechnol Lett</addtitle><addtitle>Biotechnol Lett</addtitle><description>Objectives
To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3
pro
) expressed in
Escherichia coli
BL21 (DE3) and their structure activity relationship.
Results
ZIKV NS2B-NS3
pro
was expressed in
E. coli
BL21(DE3) as a 35 kDa protein. It had a
K
m
of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3
pro
was used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3
pro
by 6.2–88%. Seven polyphenol compounds had IC
50
ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3
pro
protease. Its IC
50
value was 22 ± 0.2 µM with a
K
i
value of 8.9 ± 1.9 µM.
Conclusion
The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3
pro
can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3
pro
.</description><subject>Applied Microbiology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>E coli</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Escherichia coli</subject><subject>Flavonoids</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Inhibition</subject><subject>Life Sciences</subject><subject>Microbiology</subject><subject>Original Research Paper</subject><subject>Polyphenols</subject><subject>Polyphenols - chemistry</subject><subject>Polyphenols - pharmacology</subject><subject>Protease</subject><subject>Protease Inhibitors - chemistry</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Proteases</subject><subject>Proteins</subject><subject>Structure-Activity Relationship</subject><subject>Vector-borne diseases</subject><subject>Viral Nonstructural Proteins - antagonists & inhibitors</subject><subject>Viral Nonstructural Proteins - metabolism</subject><subject>Viruses</subject><subject>Zika virus</subject><subject>Zika Virus - enzymology</subject><issn>0141-5492</issn><issn>1573-6776</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkktrGzEUhUVpady0P6CbIuimm2n1GL02hST0YRKSRdpNN0KeuWMrjCVH0hj87yvjNKSBQFZa3O-eyzk6CL2n5DMlRH3JlAhmGkJlw5ikjXyBZlQo3kil5Es0I7SljWgNO0Jvcr4hhBhF1Gt0xJTWQhAzQ7fzsPILX2LaYRgG6AqOAx5Gt40h-j5jt3Q-5IIvr9lpc3nN8SbFAi7DnvszPz_BW5-myoUelxX4hHNJU1emBNh1xW992eEEoys-hrzym7fo1eDGDO_u3mP0-_u3X2c_m4urH_Ozk4umqw5Ko3QnpdPOCDC965jRoJXkjreqNZoYIReibRd9Lwxn4CSnjgHvtVHUgW4pP0ZfD7qbabGGvoNQkhvtJvm1Szsbnbf_T4Jf2WXcWkW0ZopVgU93AineTpCLXfvcwTi6AHHKlup6hipO6DNQqXkNXZpnoG1LWDXJK_rxEXoTpxRqaHtBwWT9dF0peqC6FHNOMNxbpMTua2IPNbG1JnZfEyvrzoeH2dxv_OtFBdgByHUUlpAenH5S9S8gKce9</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Lim, Hee-jung</creator><creator>Nguyen, Thi Thanh Hanh</creator><creator>Kim, Nahyun M.</creator><creator>Park, Jun-Seong</creator><creator>Jang, Tae-Su</creator><creator>Kim, Doman</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T7</scope><scope>7TB</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7QO</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20170301</creationdate><title>Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship</title><author>Lim, Hee-jung ; Nguyen, Thi Thanh Hanh ; Kim, Nahyun M. ; Park, Jun-Seong ; Jang, Tae-Su ; Kim, Doman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-78c66a8a95e9dac298e8763a3474980956b544bdd5932ea631a2e3d8971ae8413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Applied Microbiology</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>E coli</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Escherichia coli</topic><topic>Flavonoids</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Inhibition</topic><topic>Life Sciences</topic><topic>Microbiology</topic><topic>Original Research Paper</topic><topic>Polyphenols</topic><topic>Polyphenols - chemistry</topic><topic>Polyphenols - pharmacology</topic><topic>Protease</topic><topic>Protease Inhibitors - chemistry</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Proteases</topic><topic>Proteins</topic><topic>Structure-Activity Relationship</topic><topic>Vector-borne diseases</topic><topic>Viral Nonstructural Proteins - antagonists & inhibitors</topic><topic>Viral Nonstructural Proteins - metabolism</topic><topic>Viruses</topic><topic>Zika virus</topic><topic>Zika Virus - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Hee-jung</creatorcontrib><creatorcontrib>Nguyen, Thi Thanh Hanh</creatorcontrib><creatorcontrib>Kim, Nahyun M.</creatorcontrib><creatorcontrib>Park, Jun-Seong</creatorcontrib><creatorcontrib>Jang, Tae-Su</creatorcontrib><creatorcontrib>Kim, Doman</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database (ProQuest)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biotechnology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Hee-jung</au><au>Nguyen, Thi Thanh Hanh</au><au>Kim, Nahyun M.</au><au>Park, Jun-Seong</au><au>Jang, Tae-Su</au><au>Kim, Doman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship</atitle><jtitle>Biotechnology letters</jtitle><stitle>Biotechnol Lett</stitle><addtitle>Biotechnol Lett</addtitle><date>2017-03-01</date><risdate>2017</risdate><volume>39</volume><issue>3</issue><spage>415</spage><epage>421</epage><pages>415-421</pages><issn>0141-5492</issn><eissn>1573-6776</eissn><abstract>Objectives
To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3
pro
) expressed in
Escherichia coli
BL21 (DE3) and their structure activity relationship.
Results
ZIKV NS2B-NS3
pro
was expressed in
E. coli
BL21(DE3) as a 35 kDa protein. It had a
K
m
of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3
pro
was used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3
pro
by 6.2–88%. Seven polyphenol compounds had IC
50
ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3
pro
protease. Its IC
50
value was 22 ± 0.2 µM with a
K
i
value of 8.9 ± 1.9 µM.
Conclusion
The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3
pro
can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3
pro
.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>27885509</pmid><doi>10.1007/s10529-016-2261-6</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0141-5492 |
| ispartof | Biotechnology letters, 2017-03, Vol.39 (3), p.415-421 |
| issn | 0141-5492 1573-6776 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7088272 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Applied Microbiology Biochemistry Biomedical and Life Sciences Biotechnology E coli Electrophoresis, Polyacrylamide Gel Escherichia coli Flavonoids Flavonoids - chemistry Flavonoids - pharmacology Inhibition Life Sciences Microbiology Original Research Paper Polyphenols Polyphenols - chemistry Polyphenols - pharmacology Protease Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Proteases Proteins Structure-Activity Relationship Vector-borne diseases Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - metabolism Viruses Zika virus Zika Virus - enzymology |
| title | Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship |
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