Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
|
| Series: | Current Research in Microbial Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666517422000554 |
| _version_ | 1811202192821977088 |
|---|---|
| author | Romain Volle Luca Murer Anthony Petkidis Vardan Andriasyan Alessandro Savi Cornelia Bircher Nicole Meili Lucy Fischer Daniela Policarpo Sequeira Daniela Katharina Mark Alfonso Gomez-Gonzalez Urs F. Greber |
| author_facet | Romain Volle Luca Murer Anthony Petkidis Vardan Andriasyan Alessandro Savi Cornelia Bircher Nicole Meili Lucy Fischer Daniela Policarpo Sequeira Daniela Katharina Mark Alfonso Gomez-Gonzalez Urs F. Greber |
| author_sort | Romain Volle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:34:47Z |
| format | Article |
| id | doaj.art-d8ad84f357884e6f9c37c23057a20df8 |
| institution | Directory Open Access Journal |
| issn | 2666-5174 |
| language | English |
| last_indexed | 2024-04-12T02:34:47Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Microbial Sciences |
| spelling | doaj.art-d8ad84f357884e6f9c37c23057a20df82022-12-22T03:51:36ZengElsevierCurrent Research in Microbial Sciences2666-51742022-01-013100158Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoidsRomain Volle0Luca Murer1Anthony Petkidis2Vardan Andriasyan3Alessandro Savi4Cornelia Bircher5Nicole Meili6Lucy Fischer7Daniela Policarpo Sequeira8Daniela Katharina Mark9Alfonso Gomez-Gonzalez10Urs F. Greber11Department of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland; Life Science Zürich Graduate School, ETH and University of Zurich, 8057 Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland; Life Science Zürich Graduate School, ETH and University of Zurich, 8057 Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland; Life Science Zürich Graduate School, ETH and University of Zurich, 8057 Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland; Life Science Zürich Graduate School, ETH and University of Zurich, 8057 Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland; Life Science Zürich Graduate School, ETH and University of Zurich, 8057 Zurich, SwitzerlandDepartment of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2666517422000554SARS-CoV-2 variant of concern Omicron (BA.1)Drug repurposingMethylene blueMycophenolic acidPosaconazoleNiclosamide |
| spellingShingle | Romain Volle Luca Murer Anthony Petkidis Vardan Andriasyan Alessandro Savi Cornelia Bircher Nicole Meili Lucy Fischer Daniela Policarpo Sequeira Daniela Katharina Mark Alfonso Gomez-Gonzalez Urs F. Greber Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids Current Research in Microbial Sciences SARS-CoV-2 variant of concern Omicron (BA.1) Drug repurposing Methylene blue Mycophenolic acid Posaconazole Niclosamide |
| title | Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids |
| title_full | Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids |
| title_fullStr | Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids |
| title_full_unstemmed | Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids |
| title_short | Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids |
| title_sort | methylene blue mycophenolic acid posaconazole and niclosamide inhibit sars cov 2 omicron variant ba 1 infection of human airway epithelial organoids |
| topic | SARS-CoV-2 variant of concern Omicron (BA.1) Drug repurposing Methylene blue Mycophenolic acid Posaconazole Niclosamide |
| url | http://www.sciencedirect.com/science/article/pii/S2666517422000554 |
| work_keys_str_mv | AT romainvolle methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT lucamurer methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT anthonypetkidis methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT vardanandriasyan methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT alessandrosavi methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT corneliabircher methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT nicolemeili methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT lucyfischer methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT danielapolicarposequeira methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT danielakatharinamark methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT alfonsogomezgonzalez methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids AT ursfgreber methylenebluemycophenolicacidposaconazoleandniclosamideinhibitsarscov2omicronvariantba1infectionofhumanairwayepithelialorganoids |