Cargando…
Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study,...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918080/ https://www.ncbi.nlm.nih.gov/pubmed/33670363 http://dx.doi.org/10.3390/v13020282 |
_version_ | 1783657846350544896 |
---|---|
author | Varghese, Finny S. van Woudenbergh, Esther Overheul, Gijs J. Eleveld, Marc J. Kurver, Lisa van Heerbeek, Niels van Laarhoven, Arjan Miesen, Pascal den Hartog, Gerco de Jonge, Marien I. van Rij, Ronald P. |
author_facet | Varghese, Finny S. van Woudenbergh, Esther Overheul, Gijs J. Eleveld, Marc J. Kurver, Lisa van Heerbeek, Niels van Laarhoven, Arjan Miesen, Pascal den Hartog, Gerco de Jonge, Marien I. van Rij, Ronald P. |
author_sort | Varghese, Finny S. |
collection | PubMed |
description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing. |
format | Online Article Text |
id | pubmed-7918080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79180802021-03-02 Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro Varghese, Finny S. van Woudenbergh, Esther Overheul, Gijs J. Eleveld, Marc J. Kurver, Lisa van Heerbeek, Niels van Laarhoven, Arjan Miesen, Pascal den Hartog, Gerco de Jonge, Marien I. van Rij, Ronald P. Viruses Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing. MDPI 2021-02-11 /pmc/articles/PMC7918080/ /pubmed/33670363 http://dx.doi.org/10.3390/v13020282 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Varghese, Finny S. van Woudenbergh, Esther Overheul, Gijs J. Eleveld, Marc J. Kurver, Lisa van Heerbeek, Niels van Laarhoven, Arjan Miesen, Pascal den Hartog, Gerco de Jonge, Marien I. van Rij, Ronald P. Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro |
title | Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro |
title_full | Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro |
title_fullStr | Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro |
title_full_unstemmed | Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro |
title_short | Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro |
title_sort | berberine and obatoclax inhibit sars-cov-2 replication in primary human nasal epithelial cells in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918080/ https://www.ncbi.nlm.nih.gov/pubmed/33670363 http://dx.doi.org/10.3390/v13020282 |
work_keys_str_mv | AT varghesefinnys berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT vanwoudenberghesther berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT overheulgijsj berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT eleveldmarcj berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT kurverlisa berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT vanheerbeekniels berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT vanlaarhovenarjan berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT miesenpascal berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT denhartoggerco berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT dejongemarieni berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro AT vanrijronaldp berberineandobatoclaxinhibitsarscov2replicationinprimaryhumannasalepithelialcellsinvitro |