Signal amplification by reversible exchange for COVID-19 antiviral drug candidates
Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to fu...
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description | Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by
para
-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies. |
doi_str_mv | 10.1038/s41598-020-71282-6 |
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para
-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-71282-6</identifier><identifier>PMID: 32868801</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>639/638/11 ; 639/638/11/876 ; 639/638/11/878 ; Amides - chemistry ; Amides - pharmacology ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Betacoronavirus - drug effects ; Bile ; Chloroquine - chemistry ; Chloroquine - pharmacology ; Chronic infection ; Cirrhosis ; Coronavirus Infections - diagnosis ; Coronavirus Infections - virology ; COVID-19 ; Cyclic AMP ; Cyclic AMP response element-binding protein ; Drug Discovery - methods ; Fibrosis ; Genomes ; Hepatitis ; Hepatitis C ; Humanities and Social Sciences ; Humans ; Hydroxyproline ; Leukocytes (neutrophilic) ; Liver cirrhosis ; Liver diseases ; Lopinavir - chemistry ; Lopinavir - pharmacology ; Macrophages ; Magnetic fields ; Matrix metalloproteinase ; Metalloproteinase ; Molecular Structure ; Monocytes ; mRNA ; multidisciplinary ; Neutrophil collagenase ; Neutrophils ; NMR ; Nuclear magnetic resonance ; Nuclear Magnetic Resonance, Biomolecular ; Pandemics ; Pneumonia, Viral - diagnosis ; Pneumonia, Viral - virology ; Polarization ; Pyrazines - chemistry ; Pyrazines - pharmacology ; Ritonavir ; Ritonavir - chemistry ; Ritonavir - pharmacology ; SARS-CoV-2 ; Science ; Science (multidisciplinary) ; Stellate cells ; Transgenic mice ; Wnt protein ; β-Catenin</subject><ispartof>Scientific reports, 2020-08, Vol.10 (1), p.14290, Article 14290</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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-c474t-cd0ca0d62bcd5a0b13eedf2f81c1b90009b959b2883a5065ff5f3415062f10343</citedby><cites>FETCH-LOGICAL-c474t-cd0ca0d62bcd5a0b13eedf2f81c1b90009b959b2883a5065ff5f3415062f10343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459298/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459298/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32868801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeong, Hye Jin</creatorcontrib><creatorcontrib>Min, Sein</creatorcontrib><creatorcontrib>Chae, Heelim</creatorcontrib><creatorcontrib>Kim, Sarah</creatorcontrib><creatorcontrib>Lee, Gunwoo</creatorcontrib><creatorcontrib>Namgoong, Sung Keon</creatorcontrib><creatorcontrib>Jeong, Keunhong</creatorcontrib><title>Signal amplification by reversible exchange for COVID-19 antiviral drug candidates</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by
para
-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies.</description><subject>639/638/11</subject><subject>639/638/11/876</subject><subject>639/638/11/878</subject><subject>Amides - chemistry</subject><subject>Amides - pharmacology</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Betacoronavirus - drug effects</subject><subject>Bile</subject><subject>Chloroquine - chemistry</subject><subject>Chloroquine - pharmacology</subject><subject>Chronic infection</subject><subject>Cirrhosis</subject><subject>Coronavirus Infections - diagnosis</subject><subject>Coronavirus Infections - virology</subject><subject>COVID-19</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Drug Discovery - methods</subject><subject>Fibrosis</subject><subject>Genomes</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hydroxyproline</subject><subject>Leukocytes (neutrophilic)</subject><subject>Liver cirrhosis</subject><subject>Liver diseases</subject><subject>Lopinavir - chemistry</subject><subject>Lopinavir - pharmacology</subject><subject>Macrophages</subject><subject>Magnetic fields</subject><subject>Matrix metalloproteinase</subject><subject>Metalloproteinase</subject><subject>Molecular Structure</subject><subject>Monocytes</subject><subject>mRNA</subject><subject>multidisciplinary</subject><subject>Neutrophil collagenase</subject><subject>Neutrophils</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Pandemics</subject><subject>Pneumonia, Viral - diagnosis</subject><subject>Pneumonia, Viral - virology</subject><subject>Polarization</subject><subject>Pyrazines - chemistry</subject><subject>Pyrazines - pharmacology</subject><subject>Ritonavir</subject><subject>Ritonavir - chemistry</subject><subject>Ritonavir - pharmacology</subject><subject>SARS-CoV-2</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stellate cells</subject><subject>Transgenic mice</subject><subject>Wnt protein</subject><subject>β-Catenin</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp1kUtLAzEUhYMoVqp_wIUMuHEzmtxMpslGkPqEguBrGzKZpI1MZ2oyU-y_N7W1VMFsErjfPTn3HoSOCT4nmPKLkBEmeIoBpwMCHNJ8Bx0AzlgKFGB3691DRyG843gYiIyIfdSjwHPOMTlAT89uXKsqUdNZ5azTqnVNnRSLxJu58cEVlUnMp56oemwS2_hk-Pj2cJ0Skai6dXPnY2_pu3GiVV26UrUmHKI9q6pgjtZ3H73e3rwM79PR493D8GqU6myQtakusVa4zKHQJVO4INSY0oLlRJNCRLeiEEwUwDlVDOfMWmZpHBrnYOMGMtpHlyvdWVdMTalN3UY3cubdVPmFbJSTvyu1m8hxM5eDjAkQPAqcrQV889GZ0MqpC9pUlapN0wUJGRU5MILziJ7-Qd-bzsfFBUm4iBglGEcKVpT2TQje2I0ZguUyNblKTcbU5Hdqcil9sj3GpuUnowjQFRBiKcbgt_7-X_YLCvWiLQ</recordid><startdate>20200831</startdate><enddate>20200831</enddate><creator>Jeong, Hye Jin</creator><creator>Min, Sein</creator><creator>Chae, Heelim</creator><creator>Kim, Sarah</creator><creator>Lee, Gunwoo</creator><creator>Namgoong, Sung Keon</creator><creator>Jeong, Keunhong</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200831</creationdate><title>Signal amplification by reversible exchange for COVID-19 antiviral drug candidates</title><author>Jeong, Hye Jin ; Min, Sein ; Chae, Heelim ; Kim, Sarah ; Lee, Gunwoo ; Namgoong, Sung Keon ; Jeong, Keunhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-cd0ca0d62bcd5a0b13eedf2f81c1b90009b959b2883a5065ff5f3415062f10343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>639/638/11</topic><topic>639/638/11/876</topic><topic>639/638/11/878</topic><topic>Amides - chemistry</topic><topic>Amides - pharmacology</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Betacoronavirus - drug effects</topic><topic>Bile</topic><topic>Chloroquine - chemistry</topic><topic>Chloroquine - pharmacology</topic><topic>Chronic infection</topic><topic>Cirrhosis</topic><topic>Coronavirus Infections - diagnosis</topic><topic>Coronavirus Infections - virology</topic><topic>COVID-19</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP response element-binding protein</topic><topic>Drug Discovery - methods</topic><topic>Fibrosis</topic><topic>Genomes</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hydroxyproline</topic><topic>Leukocytes (neutrophilic)</topic><topic>Liver cirrhosis</topic><topic>Liver diseases</topic><topic>Lopinavir - chemistry</topic><topic>Lopinavir - pharmacology</topic><topic>Macrophages</topic><topic>Magnetic fields</topic><topic>Matrix metalloproteinase</topic><topic>Metalloproteinase</topic><topic>Molecular Structure</topic><topic>Monocytes</topic><topic>mRNA</topic><topic>multidisciplinary</topic><topic>Neutrophil collagenase</topic><topic>Neutrophils</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Pandemics</topic><topic>Pneumonia, Viral - diagnosis</topic><topic>Pneumonia, Viral - virology</topic><topic>Polarization</topic><topic>Pyrazines - chemistry</topic><topic>Pyrazines - pharmacology</topic><topic>Ritonavir</topic><topic>Ritonavir - chemistry</topic><topic>Ritonavir - pharmacology</topic><topic>SARS-CoV-2</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stellate cells</topic><topic>Transgenic mice</topic><topic>Wnt protein</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jeong, Hye Jin</creatorcontrib><creatorcontrib>Min, Sein</creatorcontrib><creatorcontrib>Chae, Heelim</creatorcontrib><creatorcontrib>Kim, Sarah</creatorcontrib><creatorcontrib>Lee, Gunwoo</creatorcontrib><creatorcontrib>Namgoong, Sung Keon</creatorcontrib><creatorcontrib>Jeong, Keunhong</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>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 SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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 Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI 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>Jeong, Hye Jin</au><au>Min, Sein</au><au>Chae, Heelim</au><au>Kim, Sarah</au><au>Lee, Gunwoo</au><au>Namgoong, Sung Keon</au><au>Jeong, Keunhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Signal amplification by reversible exchange for COVID-19 antiviral drug candidates</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-08-31</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>14290</spage><pages>14290-</pages><artnum>14290</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by
para
-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32868801</pmid><doi>10.1038/s41598-020-71282-6</doi><oa>free_for_read</oa></addata></record> |
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subjects | 639/638/11 639/638/11/876 639/638/11/878 Amides - chemistry Amides - pharmacology Antiviral Agents - chemistry Antiviral Agents - pharmacology Betacoronavirus - drug effects Bile Chloroquine - chemistry Chloroquine - pharmacology Chronic infection Cirrhosis Coronavirus Infections - diagnosis Coronavirus Infections - virology COVID-19 Cyclic AMP Cyclic AMP response element-binding protein Drug Discovery - methods Fibrosis Genomes Hepatitis Hepatitis C Humanities and Social Sciences Humans Hydroxyproline Leukocytes (neutrophilic) Liver cirrhosis Liver diseases Lopinavir - chemistry Lopinavir - pharmacology Macrophages Magnetic fields Matrix metalloproteinase Metalloproteinase Molecular Structure Monocytes mRNA multidisciplinary Neutrophil collagenase Neutrophils NMR Nuclear magnetic resonance Nuclear Magnetic Resonance, Biomolecular Pandemics Pneumonia, Viral - diagnosis Pneumonia, Viral - virology Polarization Pyrazines - chemistry Pyrazines - pharmacology Ritonavir Ritonavir - chemistry Ritonavir - pharmacology SARS-CoV-2 Science Science (multidisciplinary) Stellate cells Transgenic mice Wnt protein β-Catenin |
title | Signal amplification by reversible exchange for COVID-19 antiviral drug candidates |
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