Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1038/s42003-022-03101-9 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/53619 |
| Resumo: | Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA. |
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Wang, XuantingSacramento, Carolina Q.Jockusch, SteffenChaves, Otávio AugustoTao, ChuanjuanFintelman-Rodrigues, NataliaChien, MinchenTemerozo, Jairo R.Li, XiaoxuKumar, ShivXie, WeiPatel, Dinshaw J.Meyer, CindyGarzia, AitorTuschi, ThomasBozza, Patricia T.Russo, James J.Souza, Thiago Moreno L.Ju, Jingyue2022-07-04T11:44:15Z2022-07-04T11:44:15Z2022WANG, Xuanting et al. Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture. Communications Biology, v. 15, 154, p. 1-14, 2022.2399-3642https://www.arca.fiocruz.br/handle/icict/5361910.1038/s42003-022-03101-9engSpringer NatureCombinação de medicamentos antiviraisSARS-CoV-2 pilmeraseCOVID-19ExonucleasePotencial terapêuticoCultura de células viraisCOVID-19Combination of antiviral drugsInhibits SARS-CoV-2 polymerase and exonucleaseTherapeutic potentialViral cell cultureCombination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell cultureinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças da População Negligenciada. Rio de Janeiro, RJ, Brasil.Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemistry, Columbia University, New York, NY 10027, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças da População Negligenciada. Rio de Janeiro, RJ, Brasil.Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças da População Negligenciada. Rio de Janeiro, RJ, Brasil.Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.Laboratory of Structural Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.Laboratory of Structural Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10065, USA.Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10065, USA.Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10065, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA / Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY 10032, USA.SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/53619/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALJairoTemoerozo_NataliaFRodrigues_etal_IOC_2022.pdfJairoTemoerozo_NataliaFRodrigues_etal_IOC_2022.pdfapplication/pdf2804613https://www.arca.fiocruz.br/bitstream/icict/53619/2/JairoTemoerozo_NataliaFRodrigues_etal_IOC_2022.pdf69498688b96bd9bd7a9f4bbc7a47cf2cMD52icict/536192023-02-15 22:48:59.189oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-02-16T01:48:59Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture |
| title |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture |
| spellingShingle |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture Wang, Xuanting Combinação de medicamentos antivirais SARS-CoV-2 pilmerase COVID-19 Exonuclease Potencial terapêutico Cultura de células virais COVID-19 Combination of antiviral drugs Inhibits SARS-CoV-2 polymerase and exonuclease Therapeutic potential Viral cell culture |
| title_short |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture |
| title_full |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture |
| title_fullStr |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture |
| title_full_unstemmed |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture |
| title_sort |
Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture |
| author |
Wang, Xuanting |
| author_facet |
Wang, Xuanting Sacramento, Carolina Q. Jockusch, Steffen Chaves, Otávio Augusto Tao, Chuanjuan Fintelman-Rodrigues, Natalia Chien, Minchen Temerozo, Jairo R. Li, Xiaoxu Kumar, Shiv Xie, Wei Patel, Dinshaw J. Meyer, Cindy Garzia, Aitor Tuschi, Thomas Bozza, Patricia T. Russo, James J. Souza, Thiago Moreno L. Ju, Jingyue |
| author_role |
author |
| author2 |
Sacramento, Carolina Q. Jockusch, Steffen Chaves, Otávio Augusto Tao, Chuanjuan Fintelman-Rodrigues, Natalia Chien, Minchen Temerozo, Jairo R. Li, Xiaoxu Kumar, Shiv Xie, Wei Patel, Dinshaw J. Meyer, Cindy Garzia, Aitor Tuschi, Thomas Bozza, Patricia T. Russo, James J. Souza, Thiago Moreno L. Ju, Jingyue |
| author2_role |
author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Wang, Xuanting Sacramento, Carolina Q. Jockusch, Steffen Chaves, Otávio Augusto Tao, Chuanjuan Fintelman-Rodrigues, Natalia Chien, Minchen Temerozo, Jairo R. Li, Xiaoxu Kumar, Shiv Xie, Wei Patel, Dinshaw J. Meyer, Cindy Garzia, Aitor Tuschi, Thomas Bozza, Patricia T. Russo, James J. Souza, Thiago Moreno L. Ju, Jingyue |
| dc.subject.other.pt_BR.fl_str_mv |
Combinação de medicamentos antivirais SARS-CoV-2 pilmerase COVID-19 Exonuclease Potencial terapêutico Cultura de células virais |
| topic |
Combinação de medicamentos antivirais SARS-CoV-2 pilmerase COVID-19 Exonuclease Potencial terapêutico Cultura de células virais COVID-19 Combination of antiviral drugs Inhibits SARS-CoV-2 polymerase and exonuclease Therapeutic potential Viral cell culture |
| dc.subject.en.pt_BR.fl_str_mv |
COVID-19 Combination of antiviral drugs Inhibits SARS-CoV-2 polymerase and exonuclease Therapeutic potential Viral cell culture |
| description |
Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemical Engineering, Columbia University, New York, NY 10027, USA. |
| publishDate |
2022 |
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2022-07-04T11:44:15Z |
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2022-07-04T11:44:15Z |
| dc.date.issued.fl_str_mv |
2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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| dc.identifier.citation.fl_str_mv |
WANG, Xuanting et al. Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture. Communications Biology, v. 15, 154, p. 1-14, 2022. |
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https://www.arca.fiocruz.br/handle/icict/53619 |
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2399-3642 |
| dc.identifier.doi.none.fl_str_mv |
10.1038/s42003-022-03101-9 |
| identifier_str_mv |
WANG, Xuanting et al. Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture. Communications Biology, v. 15, 154, p. 1-14, 2022. 2399-3642 10.1038/s42003-022-03101-9 |
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Springer Nature |
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Springer Nature |
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