In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2
In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Despite containment measures, SARS-CoV-2 spread in Asia, Southern Europe, then in America and currently in Africa. Identifying effective antiviral...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/21/5064 |
| _version_ | 1797549147790770176 |
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| author | Mathieu Gendrot Julien Andreani Priscilla Jardot Sébastien Hutter Océane Delandre Manon Boxberger Joel Mosnier Marion Le Bideau Isabelle Duflot Isabelle Fonta Clara Rolland Hervé Bogreau Bernard La Scola Bruno Pradines |
| author_facet | Mathieu Gendrot Julien Andreani Priscilla Jardot Sébastien Hutter Océane Delandre Manon Boxberger Joel Mosnier Marion Le Bideau Isabelle Duflot Isabelle Fonta Clara Rolland Hervé Bogreau Bernard La Scola Bruno Pradines |
| author_sort | Mathieu Gendrot |
| collection | DOAJ |
| description | In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Despite containment measures, SARS-CoV-2 spread in Asia, Southern Europe, then in America and currently in Africa. Identifying effective antiviral drugs is urgently needed. An efficient approach to drug discovery is to evaluate whether existing approved drugs can be efficient against SARS-CoV-2. Doxycycline, which is a second-generation tetracycline with broad-spectrum antimicrobial, antimalarial and anti-inflammatory activities, showed in vitro activity on Vero E6 cells infected with a clinically isolated SARS-CoV-2 strain (IHUMI-3) with median effective concentration (EC<sub>50</sub>) of 4.5 ± 2.9 µM, compatible with oral uptake and intravenous administrations. Doxycycline interacted both on SARS-CoV-2 entry and in replication after virus entry. Besides its in vitro antiviral activity against SARS-CoV-2, doxycycline has anti-inflammatory effects by decreasing the expression of various pro-inflammatory cytokines and could prevent co-infections and superinfections due to broad-spectrum antimicrobial activity. Therefore, doxycycline could be a potential partner of COVID-19 therapies. However, these results must be taken with caution regarding the potential use in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results to actual clinical treatment in patients. In vivo evaluation in animal experimental models is required to confirm the antiviral effects of doxycycline on SARS-CoV-2 and more trials of high-risk patients with moderate to severe COVID-19 infections must be initiated. |
| first_indexed | 2024-03-10T15:10:34Z |
| format | Article |
| id | doaj.art-030339de52ff489da528e7f9e100d9ce |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:10:34Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-030339de52ff489da528e7f9e100d9ce2023-11-20T19:21:21ZengMDPI AGMolecules1420-30492020-10-012521506410.3390/molecules25215064In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2Mathieu Gendrot0Julien Andreani1Priscilla Jardot2Sébastien Hutter3Océane Delandre4Manon Boxberger5Joel Mosnier6Marion Le Bideau7Isabelle Duflot8Isabelle Fonta9Clara Rolland10Hervé Bogreau11Bernard La Scola12Bruno Pradines13Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceIHU Méditerranée Infection, 13005 Marseille, FranceIHU Méditerranée Infection, 13005 Marseille, FranceAix Marseille Univ, IRD, SSA, AP-HM, VITROME, 13005 Marseille, FranceUnité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceIHU Méditerranée Infection, 13005 Marseille, FranceUnité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceIHU Méditerranée Infection, 13005 Marseille, FranceIHU Méditerranée Infection, 13005 Marseille, FranceUnité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceIHU Méditerranée Infection, 13005 Marseille, FranceUnité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceIHU Méditerranée Infection, 13005 Marseille, FranceUnité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceIn December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Despite containment measures, SARS-CoV-2 spread in Asia, Southern Europe, then in America and currently in Africa. Identifying effective antiviral drugs is urgently needed. An efficient approach to drug discovery is to evaluate whether existing approved drugs can be efficient against SARS-CoV-2. Doxycycline, which is a second-generation tetracycline with broad-spectrum antimicrobial, antimalarial and anti-inflammatory activities, showed in vitro activity on Vero E6 cells infected with a clinically isolated SARS-CoV-2 strain (IHUMI-3) with median effective concentration (EC<sub>50</sub>) of 4.5 ± 2.9 µM, compatible with oral uptake and intravenous administrations. Doxycycline interacted both on SARS-CoV-2 entry and in replication after virus entry. Besides its in vitro antiviral activity against SARS-CoV-2, doxycycline has anti-inflammatory effects by decreasing the expression of various pro-inflammatory cytokines and could prevent co-infections and superinfections due to broad-spectrum antimicrobial activity. Therefore, doxycycline could be a potential partner of COVID-19 therapies. However, these results must be taken with caution regarding the potential use in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results to actual clinical treatment in patients. In vivo evaluation in animal experimental models is required to confirm the antiviral effects of doxycycline on SARS-CoV-2 and more trials of high-risk patients with moderate to severe COVID-19 infections must be initiated.https://www.mdpi.com/1420-3049/25/21/5064COVID-19SARS-CoV-2doxycyclinetreatmentprophylaxisantiviral |
| spellingShingle | Mathieu Gendrot Julien Andreani Priscilla Jardot Sébastien Hutter Océane Delandre Manon Boxberger Joel Mosnier Marion Le Bideau Isabelle Duflot Isabelle Fonta Clara Rolland Hervé Bogreau Bernard La Scola Bruno Pradines In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2 Molecules COVID-19 SARS-CoV-2 doxycycline treatment prophylaxis antiviral |
| title | In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2 |
| title_full | In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2 |
| title_fullStr | In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2 |
| title_full_unstemmed | In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2 |
| title_short | In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2 |
| title_sort | in vitro antiviral activity of doxycycline against sars cov 2 |
| topic | COVID-19 SARS-CoV-2 doxycycline treatment prophylaxis antiviral |
| url | https://www.mdpi.com/1420-3049/25/21/5064 |
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