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Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry

Morin-Dewaele et al., Scientific Reports, doi:10.1038/s41598-022-25399-5
Dec 2022  
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12th treatment shown to reduce risk in January 2021
 
*, now with p = 0.000000021 from 13 studies.
Lower risk for mortality, recovery, and cases.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
In Vitro study showing that desloratadine inhibits SARS-CoV-2 infection in Vero E6 cells, Calu-3 cells, and primary human nasal epithelial cells (HNECs) by blocking viral entry through the endosomal pathway. Authors screened 8 FDA-approved cationic amphiphilic drugs (CADs) and found that desloratadine was the most potent, with an EC50 of 0.7-0.9 μM. Desloratadine also inhibited the related coronaviruses HCoV-229E and HCoV-OC43, suggesting broad-spectrum anti-coronavirus activity. Time-of-addition experiments showed that desloratadine targets an early step of the SARS-CoV-2 lifecycle. In primary HNECs, desloratadine treatment significantly delayed viral RNA production, with maximal reduction after 72 hours. The results suggest desloratadine could potentially contribute to COVID-19 prophylaxis and therapy.
11 preclinical studies support the efficacy of antihistamine H1RAs for COVID-19:
Morin-Dewaele et al., 6 Dec 2022, France, peer-reviewed, 18 authors. Contact: hakim.ahmed-belkacem@inserm.fr.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperH1RAsAll
Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry
Margot Morin-Dewaele, Sophie Bartier, François Berry, Rozenn Brillet, Dennis Salomón López-Molina, Công Trung Nguyễn, Pascale Maille, Kevin Sereno, Quentin Nevers, Laurent Softic, Jean-Marie Vaugeois, Bruno Louis, Emilie Bequignon, Patrice Bruscella, André Coste, Jean-Michel Pawlotsky, Stéphane Jamain, Abdelhakim Ahmed-Belkacem
Scientific Reports, doi:10.1038/s41598-022-25399-5
The 2019 global coronavirus (COVID-19) pandemic has brought the world to a grinding halt, highlighting the urgent need for therapeutic and preventive solutions to slow the spread of emerging viruses. The objective of this study was to assess the anti-SARS-CoV-2 effectiveness of 8 FDAapproved cationic amphiphilic drugs (CADs). SARS-CoV-2-infected Vero cells, Calu-3 cells and primary Human Nasal Epithelial Cells (HNEC) were used to investigate the effects of CADs and revealed their antiviral mode of action. Among the CADs tested, desloratadine, a commonly used antiallergic, welltolerated with no major side effects, potently reduced the production of SARS-CoV-2 RNA in Vero-E6 cells. Interestingly, desloratadine was also effective against HCoV-229E and HCoV-OC43 showing that it possessed broad-spectrum anti-coronavirus activity. Investigation of its mode of action revealed that it targeted an early step of virus lifecycle and blocked SARS-CoV-2 entry through the endosomal pathway. Finally, the ex vivo kinetic of the antiviral effect of desloratadine was evaluated on primary Human Nasal Epithelial Cells (HNEC), showing a significant delay of viral RNA production with a maximal reduction reached after 72 h of treatment. Thus, this treatment could provide a substantial contribution to prophylaxis and systemic therapy of COVID-19 or other coronaviruses infections and requires further studies. Coronaviruses are a group of enveloped positive-sense RNA viruses. Until recently, most human infections were caused by four human coronaviruses (HCoV) inducing benign respiratory tract diseases, including HCoV-OC43, HCoV-229E, HCoV-NL63 and HKU1. In the last two decades, three zoonotic coronaviruses capable to induce severe lung disease with moderate to high lethality rates have emerged in human populations. The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) emerged in 2003 in China and caused a self-limiting outbreak 1 . In 2012, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in Saudi Arabia. This virus is rarely transmitted between humans, but has a very high lethality rate 2 . Lastly, the SARS-CoV-2, a hitherto unknown member of the Orthocoronavirinae subfamily, emerged in december 2019 in China and rapidly spread OPEN
Author contributions M.M-D.: acquisition, analysis, and interpretation of data; participation in the drafting of the manuscript. S.B.: contribution to the experimental design of experiments on primary nasal epithelial cells and acquisition, analysis, and interpretation of data, participation in the drafting of the manuscript. F.B.: acquisition, analysis, and interpretation of data. R.B. and D.L-M.: acquisition and analysis of data. C.T.N., P.M., K.S.: acquisition, analysis, and interpretation of histologic data. Q.N., L.S., J-M.V., B.L., J-M.P., A.C.: critical revision of the manuscript. E.B.: contribution to the experimental design of primary nasal epithelial, critical revision of the manuscript. P.B.: data analysis and interpretation, critical revision of the manuscript. S.J., A.A-B.: study supervision; analysis and interpretation of data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. Competing interests J-M.P. has served as an advisor and/or speaker for Abbvie, Gilead, Merck, Regulus, Assembly Biosciences, Arbutus and Memo Therapeutics. A.C. has participated in advisory boards for ALK, GSK and Sanofi. The rest of the authors have no competing interest. Additional information Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1038/ s41598-022-25399-5. Correspondence and requests for materials should be addressed to Reprints and permissions..
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The rest of the ' 'authors have no competing interest.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '21053'}
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