Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays.
Identifieur interne : 001C16 ( Main/Exploration ); précédent : 001C15; suivant : 001C17Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays.
Auteurs : Brit J. Hart [États-Unis] ; Julie Dyall [États-Unis] ; Elena Postnikova [États-Unis] ; Huanying Zhou [États-Unis] ; Jason Kindrachuk [États-Unis] ; Reed F. Johnson [États-Unis] ; Gene G. Olinger [États-Unis] ; Matthew B. Frieman [États-Unis] ; Michael R. Holbrook [États-Unis] ; Peter B. Jahrling [États-Unis] ; Lisa Hensley [États-Unis]Source :
- The Journal of general virology [ 1465-2099 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
- pharmacologie : Acide mycophénolique, Interférons.
- physiologie : Coronaviridae.
- traitement médicamenteux : Infections à Coronaviridae.
- virologie : Infections à Coronaviridae.
- Animaux, Cellules Vero, Coronaviridae, Humains, Lignée cellulaire, Réplication virale.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Interferons, Mycophenolic Acid.
- drug effects : Coronaviridae, Virus Replication.
- drug therapy : Coronaviridae Infections.
- physiology : Coronaviridae.
- virology : Coronaviridae Infections.
- Animals, Cell Line, Chlorocebus aethiops, Humans, Vero Cells.
Abstract
The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC₅₀ of 1.37 U ml(-1), 41 times lower than the previously reported IC₅₀ (56.08 U ml(-1)) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml(-1). Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC₅₀ of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.
DOI: 10.1099/vir.0.061911-0
PubMed: 24323636
Affiliations:
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Johnson</name><affiliation wicri:level="2"><nlm:affiliation>Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Olinger, Gene G" sort="Olinger, Gene G" uniqKey="Olinger G" first="Gene G" last="Olinger">Gene G. Olinger</name><affiliation wicri:level="2"><nlm:affiliation>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Holbrook, Michael R" sort="Holbrook, Michael R" uniqKey="Holbrook M" first="Michael R" last="Holbrook">Michael R. Holbrook</name><affiliation wicri:level="2"><nlm:affiliation>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B" last="Jahrling">Peter B. Jahrling</name><affiliation wicri:level="2"><nlm:affiliation>Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Hensley, Lisa" sort="Hensley, Lisa" uniqKey="Hensley L" first="Lisa" last="Hensley">Lisa Hensley</name><affiliation wicri:level="2"><nlm:affiliation>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of general virology</title><idno type="eISSN">1465-2099</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Coronaviridae (drug effects)</term><term>Coronaviridae (physiology)</term><term>Coronaviridae Infections (drug therapy)</term><term>Coronaviridae Infections (virology)</term><term>Humans</term><term>Interferons (pharmacology)</term><term>Mycophenolic Acid (pharmacology)</term><term>Vero Cells</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide mycophénolique (pharmacologie)</term><term>Animaux</term><term>Cellules Vero</term><term>Coronaviridae ()</term><term>Coronaviridae (physiologie)</term><term>Humains</term><term>Infections à Coronaviridae (traitement médicamenteux)</term><term>Infections à Coronaviridae (virologie)</term><term>Interférons (pharmacologie)</term><term>Lignée cellulaire</term><term>Réplication virale ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Interferons</term><term>Mycophenolic Acid</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronaviridae</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronaviridae Infections</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acide mycophénolique</term><term>Interférons</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronaviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Coronaviridae</term><term>Humains</term><term>Lignée cellulaire</term><term>Réplication virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC₅₀ of 1.37 U ml(-1), 41 times lower than the previously reported IC₅₀ (56.08 U ml(-1)) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml(-1). Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC₅₀ of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Hart, Brit J" sort="Hart, Brit J" uniqKey="Hart B" first="Brit J" last="Hart">Brit J. Hart</name></region><name sortKey="Dyall, Julie" sort="Dyall, Julie" uniqKey="Dyall J" first="Julie" last="Dyall">Julie Dyall</name><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name><name sortKey="Hensley, Lisa" sort="Hensley, Lisa" uniqKey="Hensley L" first="Lisa" last="Hensley">Lisa Hensley</name><name sortKey="Holbrook, Michael R" sort="Holbrook, Michael R" uniqKey="Holbrook M" first="Michael R" last="Holbrook">Michael R. Holbrook</name><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B" last="Jahrling">Peter B. Jahrling</name><name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F" last="Johnson">Reed F. Johnson</name><name sortKey="Kindrachuk, Jason" sort="Kindrachuk, Jason" uniqKey="Kindrachuk J" first="Jason" last="Kindrachuk">Jason Kindrachuk</name><name sortKey="Olinger, Gene G" sort="Olinger, Gene G" uniqKey="Olinger G" first="Gene G" last="Olinger">Gene G. Olinger</name><name sortKey="Postnikova, Elena" sort="Postnikova, Elena" uniqKey="Postnikova E" first="Elena" last="Postnikova">Elena Postnikova</name><name sortKey="Zhou, Huanying" sort="Zhou, Huanying" uniqKey="Zhou H" first="Huanying" last="Zhou">Huanying Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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