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

• Published in: Current research in microbial sciences 2022, Vol.3, p.100158-100158, Article 100158
• Main Authors: Volle, Romain, Murer, Luca, Petkidis, Anthony, Andriasyan, Vardan, Savi, Alessandro, Bircher, Cornelia, Meili, Nicole, Fischer, Lucy, Sequeira, Daniela Policarpo, Mark, Daniela Katharina, Gomez-Gonzalez, Alfonso, Greber, Urs F.
• Format: Article
• Language: English
• Subjects: Drug repurposing; Human nasal and bronchial epithelial explant cultures; Methylene blue; Mycophenolic acid; Niclosamide; Persistent infection; Posaconazole; SARS-CoV-2 variant of concern Omicron (BA.1)
• ISSN: 2666-5174; 2666-5174
• DOI: 10.1016/j.crmicr.2022.100158

•Methylene blue, mycophenolate, posaconazole and niclosamide inhibit SARS-CoV-2 VoC Omicron BA.1 infection of primary human airway organoids.•Inhibition occurs upon post-exposure drug treatment and without overt cell toxicity.•SARS-CoV-2 Omicron BA.1 infection of human airway organoids persists for at least three weeks without apparent cell lesion indicated by ORF1ab FISH staining of infected cells. 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) (Weiss et al., 2021, Murer et al., 2022). Our results here not only reinforce the 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 d, and maintains both intracellular and extracellular viral genomic RNA without overt toxicity, suggesting viral persistence. The data emphasize the potential of repurposable drugs against COVID-19. [Display omitted]