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Details

Autor(en) / Beteiligte
Titel
Clofazimine broadly inhibits coronaviruses including SARS-CoV-2
Ist Teil von
  • Nature (London), 2021-05, Vol.593 (7859), p.418-423
Ort / Verlag
England: Nature Publishing Group
Erscheinungsjahr
2021
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012 . Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile -possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.
Sprache
Englisch
Identifikatoren
ISSN: 0028-0836
eISSN: 1476-4687
DOI: 10.1038/s41586-021-03431-4
Titel-ID: cdi_proquest_journals_2531705321
Format
Schlagworte
Adenosine Monophosphate - analogs & derivatives, Adenosine Monophosphate - pharmacology, Adenosine Monophosphate - therapeutic use, Alanine - analogs & derivatives, Alanine - pharmacology, Alanine - therapeutic use, Animals, Anti-Inflammatory Agents - pharmacokinetics, Anti-Inflammatory Agents - pharmacology, Anti-Inflammatory Agents - therapeutic use, Antiviral Agents - pharmacokinetics, Antiviral Agents - pharmacology, Antiviral Agents - therapeutic use, Bioavailability, Biological Availability, Cell Fusion, Cell Line, Clofazimine, Clofazimine - pharmacokinetics, Clofazimine - pharmacology, Clofazimine - therapeutic use, Coronaviridae, Coronavirus - classification, Coronavirus - drug effects, Coronavirus - growth & development, Coronavirus - pathogenicity, Coronaviruses, COVID-19, Cricetinae, DNA helicase, DNA Helicases - antagonists & inhibitors, Dosage and administration, Drug Synergism, Female, Glycoproteins, Health services, Humans, Inflammation, Leprosy, Life Cycle Stages - drug effects, Male, Mesocricetus, Middle East respiratory syndrome, Mortality, Pandemics, Pathogenesis, Pre-Exposure Prophylaxis, Respiratory diseases, Respiratory tract, SARS-CoV-2 - drug effects, SARS-CoV-2 - growth & development, Severe acute respiratory syndrome, Severe acute respiratory syndrome coronavirus 2, Shedding, Species Specificity, Spike glycoprotein, Spike Glycoprotein, Coronavirus - antagonists & inhibitors, Transcription, Genetic - drug effects, Transcription, Genetic - genetics, Viral diseases, Zoonoses

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