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Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines
COVID-19 is marked by extensive damage to the respiratory system, often accompanied by systemic manifestations, due to both viral cytopathic effects and hyperinflammatory syndrome. Therefore, the development of new therapeutic strategies or drug repurposing aiming to control virus replication and in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Authors. Published by Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250893/ https://www.ncbi.nlm.nih.gov/pubmed/35798224 http://dx.doi.org/10.1016/j.antiviral.2022.105373 |
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author | Bezerra, Bruno Braz Silva, Gustavo Peixoto Duarte da Coelho, Sharton Vinicius Antunes Correa, Isadora Alonso Souza, Marcos Romario Matos de Macedo, Keylla Vitória Gomes Matos, Bruna Machado Tanuri, Amilcar Matassoli, Flavio Lemos Costa, Luciana Jesus da Hildreth, James E.K. Arruda, Luciana Barros de |
author_facet | Bezerra, Bruno Braz Silva, Gustavo Peixoto Duarte da Coelho, Sharton Vinicius Antunes Correa, Isadora Alonso Souza, Marcos Romario Matos de Macedo, Keylla Vitória Gomes Matos, Bruna Machado Tanuri, Amilcar Matassoli, Flavio Lemos Costa, Luciana Jesus da Hildreth, James E.K. Arruda, Luciana Barros de |
author_sort | Bezerra, Bruno Braz |
collection | PubMed |
description | COVID-19 is marked by extensive damage to the respiratory system, often accompanied by systemic manifestations, due to both viral cytopathic effects and hyperinflammatory syndrome. Therefore, the development of new therapeutic strategies or drug repurposing aiming to control virus replication and inflammation are required to mitigate the impact of the disease. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent with antiviral activity that has been demonstrated against enveloped viruses in in vitro and in vivo experimental models. We also demonstrated that HP-BCD has an immunomodulatory effect, inhibiting the production of selected proinflammatory cytokines induced by microbial products. Importantly, this drug has been used in humans for decades as an excipient in drug delivery systems and as a therapeutic agent in the treatment of Niemann pick C disease. The safety profile for this compound is well established. Here, we investigated whether HP-BCD would affect SARS-CoV-2 replication and virus-induced inflammatory response, using established cell lines and primary human cells. Treating virus or cells with HP-BCD significantly inhibited SARS-CoV-2 replication with a high selective index. A broad activity against distinct SARS-CoV-2 variants was evidenced by a remarkable reduction in the release of infectious particles. The drug did not alter ACE2 surface expression, but affected cholesterol accumulation into intracellular replication complexes, lowering virus RNA and protein levels, and reducing virus-induced cytopathic effects. Virus replication was also impaired by HP-BCD in Calu-3 pulmonary cell line and human primary monocytes, in which not only the virus, but also the production of proinflammatory cytokines were significantly inhibited. Given the pathophysiology of COVID-19 disease, these data indicate that the use HP-BCD, which inhibits both SARS-CoV2 replication and production of proinflammatory cytokines, as a potential COVID-19 therapeutic warrants further investigation. |
format | Online Article Text |
id | pubmed-9250893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Authors. Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92508932022-07-05 Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines Bezerra, Bruno Braz Silva, Gustavo Peixoto Duarte da Coelho, Sharton Vinicius Antunes Correa, Isadora Alonso Souza, Marcos Romario Matos de Macedo, Keylla Vitória Gomes Matos, Bruna Machado Tanuri, Amilcar Matassoli, Flavio Lemos Costa, Luciana Jesus da Hildreth, James E.K. Arruda, Luciana Barros de Antiviral Res Article COVID-19 is marked by extensive damage to the respiratory system, often accompanied by systemic manifestations, due to both viral cytopathic effects and hyperinflammatory syndrome. Therefore, the development of new therapeutic strategies or drug repurposing aiming to control virus replication and inflammation are required to mitigate the impact of the disease. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent with antiviral activity that has been demonstrated against enveloped viruses in in vitro and in vivo experimental models. We also demonstrated that HP-BCD has an immunomodulatory effect, inhibiting the production of selected proinflammatory cytokines induced by microbial products. Importantly, this drug has been used in humans for decades as an excipient in drug delivery systems and as a therapeutic agent in the treatment of Niemann pick C disease. The safety profile for this compound is well established. Here, we investigated whether HP-BCD would affect SARS-CoV-2 replication and virus-induced inflammatory response, using established cell lines and primary human cells. Treating virus or cells with HP-BCD significantly inhibited SARS-CoV-2 replication with a high selective index. A broad activity against distinct SARS-CoV-2 variants was evidenced by a remarkable reduction in the release of infectious particles. The drug did not alter ACE2 surface expression, but affected cholesterol accumulation into intracellular replication complexes, lowering virus RNA and protein levels, and reducing virus-induced cytopathic effects. Virus replication was also impaired by HP-BCD in Calu-3 pulmonary cell line and human primary monocytes, in which not only the virus, but also the production of proinflammatory cytokines were significantly inhibited. Given the pathophysiology of COVID-19 disease, these data indicate that the use HP-BCD, which inhibits both SARS-CoV2 replication and production of proinflammatory cytokines, as a potential COVID-19 therapeutic warrants further investigation. The Authors. Published by Elsevier B.V. 2022-09 2022-07-04 /pmc/articles/PMC9250893/ /pubmed/35798224 http://dx.doi.org/10.1016/j.antiviral.2022.105373 Text en © 2022 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Bezerra, Bruno Braz Silva, Gustavo Peixoto Duarte da Coelho, Sharton Vinicius Antunes Correa, Isadora Alonso Souza, Marcos Romario Matos de Macedo, Keylla Vitória Gomes Matos, Bruna Machado Tanuri, Amilcar Matassoli, Flavio Lemos Costa, Luciana Jesus da Hildreth, James E.K. Arruda, Luciana Barros de Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines |
title | Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines |
title_full | Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines |
title_fullStr | Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines |
title_full_unstemmed | Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines |
title_short | Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines |
title_sort | hydroxypropyl-beta-cyclodextrin (hp-bcd) inhibits sars-cov-2 replication and virus-induced inflammatory cytokines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250893/ https://www.ncbi.nlm.nih.gov/pubmed/35798224 http://dx.doi.org/10.1016/j.antiviral.2022.105373 |
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