In Vivo Activity of Amodiaquine against Ebola Virus Infection
During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the...
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| Veröffentlicht in: | Scientific reports 2019-12, Vol.9 (1), p.20199-12, Article 20199 |
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| creator | DeWald, Lisa Evans Johnson, Joshua C. Gerhardt, Dawn M. Torzewski, Lisa M. Postnikova, Elena Honko, Anna N. Janosko, Krisztina Huzella, Louis Dowling, William E. Eakin, Ann E. Osborn, Blaire L. Gahagen, Janet Tang, Liang Green, Carol E. Mirsalis, Jon C. Holbrook, Michael R. Jahrling, Peter B. Dyall, Julie Hensley, Lisa E. |
| description | During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral. |
| doi_str_mv | 10.1038/s41598-019-56481-0 |
| format | Article |
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In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-56481-0</identifier><identifier>PMID: 31882748</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/106 ; 631/326/596/2042 ; 64 ; 692/699/255/2514 ; Amodiaquine ; Amodiaquine - therapeutic use ; Animal diseases ; Animals ; Antimalarial agents ; Antiviral Agents - therapeutic use ; Artemether ; Artemisinin ; Artemisinins - therapeutic use ; Artesunate ; Disease Models, Animal ; Drug Combinations ; Ebola virus ; Ebolavirus ; Epidemics ; Female ; Hemorrhagic Fever, Ebola - drug therapy ; Humanities and Social Sciences ; Macaca mulatta ; Malaria ; Male ; multidisciplinary ; Public health ; Science ; Science (multidisciplinary) ; Vector-borne diseases</subject><ispartof>Scientific reports, 2019-12, Vol.9 (1), p.20199-12, Article 20199</ispartof><rights>The Author(s) 2019</rights><rights>2019. 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In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. 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In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31882748</pmid><doi>10.1038/s41598-019-56481-0</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-9165-148X</orcidid><orcidid>https://orcid.org/0000-0002-0824-2667</orcidid><orcidid>https://orcid.org/0000-0002-9856-4183</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/106 631/326/596/2042 64 692/699/255/2514 Amodiaquine Amodiaquine - therapeutic use Animal diseases Animals Antimalarial agents Antiviral Agents - therapeutic use Artemether Artemisinin Artemisinins - therapeutic use Artesunate Disease Models, Animal Drug Combinations Ebola virus Ebolavirus Epidemics Female Hemorrhagic Fever, Ebola - drug therapy Humanities and Social Sciences Macaca mulatta Malaria Male multidisciplinary Public health Science Science (multidisciplinary) Vector-borne diseases |
| title | In Vivo Activity of Amodiaquine against Ebola Virus Infection |
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