Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2Omicron variant BA.1 infection of human airway epithelial explant cultures

Sublineages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron variants continue to amass mutations in the spike (S) glycoprotein, which leads to immune evasion and rapid spread of the virus across the human population. Here we demonstrate the susceptibility of the Omicron varia...

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Bibliographic Details
Published in:bioRxiv 2022-03
Main Authors: Volle, Romain, Murer, Luca, Petkidis, Anthony, Andriasyan, Vardan, Savi, Alessandro, Bircher, Cornelia, Meili, Nicole, Fisher, Lucy, Daniela Policarpo Sequeira, Daniela Katharina Mark, Alfonso Gomez Gonzalez, Greber, Urs F
Format: Article
Language:English
Subjects:
Clinical trials
Coronaviruses
COVID-19
Immunosuppressive agents
Methylene blue
Mycophenolic acid
Niclosamide
Posaconazole
Respiratory tract
Severe acute respiratory syndrome coronavirus 2
Toxicity
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Summary:Sublineages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron variants continue to amass mutations in the spike (S) glycoprotein, which leads to immune evasion and rapid spread of the virus across the human population. Here we demonstrate the susceptibility of the Omicron variant BA.1 (B.1.1.529.1) to four repurposable drugs, Methylene blue (MB), Mycophenolic acid (MPA), Posaconazole (POS), and Niclosamide (Niclo) in post-exposure treatments of primary human airway cell cultures. MB, MPA, POS, and Niclo are known to block infection of human nasal and bronchial airway epithelial explant cultures (HAEEC) with the Wuhan strain, and four variants of concern (VoC), Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28), Delta (B.1.617.2) (1, 2). Our results not only show broad anti-coronavirus effects of MB, MPA, POS and Niclo, but also demonstrate that the Omicron variant BA.1 (B.1.1.529.1) sheds infectious virus from HAEEC over at least 15 days, and maintains both intracellular and extracellular viral genomic RNA without overt toxicity, suggesting viral persistence. The data underscore the broad effects of MB, MPA, POS, and Niclo against SARS-CoV-2 and the currently circulating VoC, and reinforce the concept of repurposing drugs in clinical trials against COVID-19. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2022.03.30.486461