Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
Identifieur interne : 000254 ( Main/Exploration ); précédent : 000253; suivant : 000255Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
Auteurs : Timothy P. Sheahan [États-Unis] ; Amy C. Sims [États-Unis] ; Sarah R. Leist [États-Unis] ; Alexandra Sch Fer [États-Unis] ; John Won [États-Unis] ; Ariane J. Brown [États-Unis] ; Stephanie A. Montgomery [États-Unis] ; Alison Hogg [États-Unis] ; Darius Babusis [États-Unis] ; Michael O. Clarke [États-Unis] ; Jamie E. Spahn [États-Unis] ; Laura Bauer [États-Unis] ; Scott Sellers [États-Unis] ; Danielle Porter [États-Unis] ; Joy Y. Feng [États-Unis] ; Tomas Cihlar [États-Unis] ; Robert Jordan [États-Unis] ; Mark R. Denison [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2020.
Descripteurs français
- KwdFr :
- AMP (analogues et dérivés), AMP (usage thérapeutique), Alanine (analogues et dérivés), Alanine (usage thérapeutique), Animaux, Antiviraux (usage thérapeutique), Association médicamenteuse, Carboxylesterase (génétique), Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient (), Femelle, Humains, Infections à coronavirus (anatomopathologie), Infections à coronavirus (traitement médicamenteux), Interféron bêta (usage thérapeutique), Lopinavir (usage thérapeutique), Lésion pulmonaire (anatomopathologie), Mâle, Ritonavir (usage thérapeutique), Réplication virale (), Souris, Souris knockout.
- MESH :
- analogues et dérivés : AMP, Alanine.
- anatomopathologie : Infections à coronavirus, Lésion pulmonaire.
- génétique : Carboxylesterase.
- traitement médicamenteux : Infections à coronavirus.
- usage thérapeutique : AMP, Alanine, Antiviraux, Interféron bêta, Lopinavir, Ritonavir.
- Animaux, Association médicamenteuse, Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient, Femelle, Humains, Mâle, Réplication virale, Souris, Souris knockout.
English descriptors
- KwdEn :
- Adenosine Monophosphate (analogs & derivatives), Adenosine Monophosphate (therapeutic use), Alanine (analogs & derivatives), Alanine (therapeutic use), Animals, Antiviral Agents (therapeutic use), Carboxylesterase (genetics), Coronavirus Infections (drug therapy), Coronavirus Infections (pathology), Drug Combinations, Drug Development, Female, Humans, Interferon-beta (therapeutic use), Lopinavir (therapeutic use), Lung Injury (pathology), Male, Mice, Mice, Knockout, Middle East Respiratory Syndrome Coronavirus (drug effects), Ritonavir (therapeutic use), Viral Load, Virus Replication (drug effects).
- MESH :
- chemical , analogs & derivatives : Adenosine Monophosphate, Alanine.
- chemical , genetics : Carboxylesterase.
- chemical , therapeutic use : Adenosine Monophosphate, Alanine, Antiviral Agents, Interferon-beta, Lopinavir, Ritonavir.
- drug effects : Middle East Respiratory Syndrome Coronavirus, Virus Replication.
- drug therapy : Coronavirus Infections.
- pathology : Coronavirus Infections, Lung Injury.
- Animals, Drug Combinations, Drug Development, Female, Humans, Male, Mice, Mice, Knockout, Viral Load.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.
Url:
DOI: 10.1038/s41467-019-13940-6
PubMed: 31924756
PubMed Central: 6954302
Affiliations:
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Le document en format XML
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Chapel Hill, NC USA</nlm:aff>
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Chapel Hill, NC USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
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Foster City, CA USA</nlm:aff>
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</author>
<author><name sortKey="Babusis, Darius" sort="Babusis, Darius" uniqKey="Babusis D" first="Darius" last="Babusis">Darius Babusis</name>
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Foster City, CA USA</nlm:aff>
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<author><name sortKey="Clarke, Michael O" sort="Clarke, Michael O" uniqKey="Clarke M" first="Michael O." last="Clarke">Michael O. Clarke</name>
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Foster City, CA USA</nlm:aff>
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<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Spahn, Jamie E" sort="Spahn, Jamie E" uniqKey="Spahn J" first="Jamie E." last="Spahn">Jamie E. Spahn</name>
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<institution-id institution-id-type="GRID">grid.418227.a</institution-id>
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Foster City, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Bauer, Laura" sort="Bauer, Laura" uniqKey="Bauer L" first="Laura" last="Bauer">Laura Bauer</name>
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<institution-id institution-id-type="GRID">grid.418227.a</institution-id>
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Foster City, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Sellers, Scott" sort="Sellers, Scott" uniqKey="Sellers S" first="Scott" last="Sellers">Scott Sellers</name>
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<institution-id institution-id-type="GRID">grid.418227.a</institution-id>
<institution>Gilead Sciences, Inc,</institution>
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Foster City, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Foster City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Porter, Danielle" sort="Porter, Danielle" uniqKey="Porter D" first="Danielle" last="Porter">Danielle Porter</name>
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<institution-id institution-id-type="GRID">grid.418227.a</institution-id>
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Foster City, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Foster City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Feng, Joy Y" sort="Feng, Joy Y" uniqKey="Feng J" first="Joy Y." last="Feng">Joy Y. Feng</name>
<affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0402 1634</institution-id>
<institution-id institution-id-type="GRID">grid.418227.a</institution-id>
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Foster City, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Foster City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name>
<affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0402 1634</institution-id>
<institution-id institution-id-type="GRID">grid.418227.a</institution-id>
<institution>Gilead Sciences, Inc,</institution>
</institution-wrap>
Foster City, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Foster City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name>
<affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0402 1634</institution-id>
<institution-id institution-id-type="GRID">grid.418227.a</institution-id>
<institution>Gilead Sciences, Inc,</institution>
</institution-wrap>
Foster City, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Foster City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name>
<affiliation wicri:level="2"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 9916</institution-id>
<institution-id institution-id-type="GRID">grid.412807.8</institution-id>
<institution>Department of Pediatrics-Infectious Diseases, Department of Pathology, Microbiology and Immunology,</institution>
<institution>Vanderbilt University Medical Center,</institution>
</institution-wrap>
Nashville, TN USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000122483208</institution-id>
<institution-id institution-id-type="GRID">grid.10698.36</institution-id>
<institution>Department of Epidemiology,</institution>
<institution>University of North Carolina at Chapel Hill,</institution>
</institution-wrap>
Chapel Hill, NC USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Chapel Hill</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2020">2020</date>
</imprint>
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<term>Adenosine Monophosphate (therapeutic use)</term>
<term>Alanine (analogs & derivatives)</term>
<term>Alanine (therapeutic use)</term>
<term>Animals</term>
<term>Antiviral Agents (therapeutic use)</term>
<term>Carboxylesterase (genetics)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (pathology)</term>
<term>Drug Combinations</term>
<term>Drug Development</term>
<term>Female</term>
<term>Humans</term>
<term>Interferon-beta (therapeutic use)</term>
<term>Lopinavir (therapeutic use)</term>
<term>Lung Injury (pathology)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term>
<term>Ritonavir (therapeutic use)</term>
<term>Viral Load</term>
<term>Virus Replication (drug effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>AMP (analogues et dérivés)</term>
<term>AMP (usage thérapeutique)</term>
<term>Alanine (analogues et dérivés)</term>
<term>Alanine (usage thérapeutique)</term>
<term>Animaux</term>
<term>Antiviraux (usage thérapeutique)</term>
<term>Association médicamenteuse</term>
<term>Carboxylesterase (génétique)</term>
<term>Charge virale</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term>
<term>Femelle</term>
<term>Humains</term>
<term>Infections à coronavirus (anatomopathologie)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Interféron bêta (usage thérapeutique)</term>
<term>Lopinavir (usage thérapeutique)</term>
<term>Lésion pulmonaire (anatomopathologie)</term>
<term>Mâle</term>
<term>Ritonavir (usage thérapeutique)</term>
<term>Réplication virale ()</term>
<term>Souris</term>
<term>Souris knockout</term>
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<term>Alanine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carboxylesterase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Adenosine Monophosphate</term>
<term>Alanine</term>
<term>Antiviral Agents</term>
<term>Interferon-beta</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>AMP</term>
<term>Alanine</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Lésion pulmonaire</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Carboxylesterase</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Lung Injury</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>AMP</term>
<term>Alanine</term>
<term>Antiviraux</term>
<term>Interféron bêta</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Drug Combinations</term>
<term>Drug Development</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Association médicamenteuse</term>
<term>Charge virale</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Réplication virale</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en"><p id="Par1">Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.</p>
</div>
</front>
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<author><name sortKey="Lindenmann, J" uniqKey="Lindenmann J">J Lindenmann</name>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Channappanavar, R" uniqKey="Channappanavar R">R Channappanavar</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Li, K" uniqKey="Li K">K Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name>
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</analytic>
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</analytic>
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</analytic>
</biblStruct>
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</author>
</analytic>
</biblStruct>
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</author>
<author><name sortKey="Davis, Ic" uniqKey="Davis I">IC Davis</name>
</author>
</analytic>
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</author>
</analytic>
</biblStruct>
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</author>
</analytic>
</biblStruct>
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</author>
</analytic>
</biblStruct>
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</author>
</analytic>
</biblStruct>
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<biblStruct><analytic><author><name sortKey="Nair, Ab" uniqKey="Nair A">AB Nair</name>
</author>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Livak, Kj" uniqKey="Livak K">KJ Livak</name>
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<author><name sortKey="Schmittgen, Td" uniqKey="Schmittgen T">TD Schmittgen</name>
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<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Caroline du Nord</li>
<li>Tennessee</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Sheahan, Timothy P" sort="Sheahan, Timothy P" uniqKey="Sheahan T" first="Timothy P." last="Sheahan">Timothy P. Sheahan</name>
</region>
<name sortKey="Babusis, Darius" sort="Babusis, Darius" uniqKey="Babusis D" first="Darius" last="Babusis">Darius Babusis</name>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<name sortKey="Bauer, Laura" sort="Bauer, Laura" uniqKey="Bauer L" first="Laura" last="Bauer">Laura Bauer</name>
<name sortKey="Brown, Ariane J" sort="Brown, Ariane J" uniqKey="Brown A" first="Ariane J." last="Brown">Ariane J. Brown</name>
<name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name>
<name sortKey="Clarke, Michael O" sort="Clarke, Michael O" uniqKey="Clarke M" first="Michael O." last="Clarke">Michael O. Clarke</name>
<name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name>
<name sortKey="Feng, Joy Y" sort="Feng, Joy Y" uniqKey="Feng J" first="Joy Y." last="Feng">Joy Y. Feng</name>
<name sortKey="Hogg, Alison" sort="Hogg, Alison" uniqKey="Hogg A" first="Alison" last="Hogg">Alison Hogg</name>
<name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name>
<name sortKey="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R." last="Leist">Sarah R. Leist</name>
<name sortKey="Montgomery, Stephanie A" sort="Montgomery, Stephanie A" uniqKey="Montgomery S" first="Stephanie A." last="Montgomery">Stephanie A. Montgomery</name>
<name sortKey="Porter, Danielle" sort="Porter, Danielle" uniqKey="Porter D" first="Danielle" last="Porter">Danielle Porter</name>
<name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name>
<name sortKey="Sellers, Scott" sort="Sellers, Scott" uniqKey="Sellers S" first="Scott" last="Sellers">Scott Sellers</name>
<name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</name>
<name sortKey="Spahn, Jamie E" sort="Spahn, Jamie E" uniqKey="Spahn J" first="Jamie E." last="Spahn">Jamie E. Spahn</name>
<name sortKey="Won, John" sort="Won, John" uniqKey="Won J" first="John" last="Won">John Won</name>
</country>
</tree>
</affiliations>
</record>
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