Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissionsoup.com..
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in human with an overall case-fatality rate of >35%. Effective antivirals are crucial for improving the clinical outcome of MERS. Although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. We assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil [MMF], lopinavir/ritonavir, and interferon-β1b) in common marmosets with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated and interferon-β1b-treated animals had better outcome than the untreated animals, with improved clinical (mean clinical scores ↓50.9%-95.0% and ↓weight loss than the untreated animals), radiological (minimal pulmonary infiltrates), and pathological (mild bronchointerstitial pneumonia) findings, and lower mean viral loads in necropsied lung (↓0.59-1.06 log10 copies/glyceraldehyde 3-phosphate dehydrogenase [GAPDH]; P < .050) and extrapulmonary (↓0.11-1.29 log10 copies/GAPDH; P < .050 in kidney) tissues. In contrast, all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads (↑0.15-0.54 log10 copies/GAPDH) than the untreated animals. The mortality rate at 36 hours postinoculation was 67% (untreated and MMF-treated) versus 0-33% (lopinavir/ritonavir-treated and interferon-β1b-treated). Lopinavir/ritonavir and interferon-β1b alone or in combination should be evaluated in clinical trials. MMF alone may worsen MERS and should not be used.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:212 |
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| Enthalten in: |
The Journal of infectious diseases - 212(2015), 12 vom: 15. Dez., Seite 1904-13 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chan, Jasper Fuk-Woo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.03.2016 Date Revised 03.04.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1093/infdis/jiv392 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset |
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| 520 | |a © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in human with an overall case-fatality rate of >35%. Effective antivirals are crucial for improving the clinical outcome of MERS. Although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. We assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil [MMF], lopinavir/ritonavir, and interferon-β1b) in common marmosets with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated and interferon-β1b-treated animals had better outcome than the untreated animals, with improved clinical (mean clinical scores ↓50.9%-95.0% and ↓weight loss than the untreated animals), radiological (minimal pulmonary infiltrates), and pathological (mild bronchointerstitial pneumonia) findings, and lower mean viral loads in necropsied lung (↓0.59-1.06 log10 copies/glyceraldehyde 3-phosphate dehydrogenase [GAPDH]; P < .050) and extrapulmonary (↓0.11-1.29 log10 copies/GAPDH; P < .050 in kidney) tissues. In contrast, all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads (↑0.15-0.54 log10 copies/GAPDH) than the untreated animals. The mortality rate at 36 hours postinoculation was 67% (untreated and MMF-treated) versus 0-33% (lopinavir/ritonavir-treated and interferon-β1b-treated). Lopinavir/ritonavir and interferon-β1b alone or in combination should be evaluated in clinical trials. MMF alone may worsen MERS and should not be used | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a lopinavir | |
| 650 | 4 | |a mycophenolate | |
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| 700 | 1 | |a Yao, Yanfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yeung, Man-Lung |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Linlin |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Lilong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fengdi |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Chong |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Pin |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Jian-Piao |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Hin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Honglin |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
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