Author | Wang, Xuanting | |
Author | Sacramento, Carolina Q. | |
Author | Jockusch, Steffen | |
Author | Chaves, Otávio Augusto | |
Author | Tao, Chuanjuan | |
Author | Fintelman-Rodrigues, Natalia | |
Author | Chien, Minchen | |
Author | Temerozo, Jairo R. | |
Author | Li, Xiaoxu | |
Author | Kumar, Shiv | |
Author | Xie, Wei | |
Author | Patel, Dinshaw J. | |
Author | Meyer, Cindy | |
Author | Garzia, Aitor | |
Author | Tuschi, Thomas | |
Author | Bozza, Patricia T. | |
Author | Russo, James J. | |
Author | Souza, Thiago Moreno L. | |
Author | Ju, Jingyue | |
Access date | 2022-07-04T11:44:15Z | |
Available date | 2022-07-04T11:44:15Z | |
Document date | 2022 | |
Citation | 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. | pt_BR |
ISSN | 2399-3642 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/53619 | |
Language | eng | pt_BR |
Publisher | Springer Nature | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Combinação de medicamentos antivirais | pt_BR |
Subject in Portuguese | SARS-CoV-2 pilmerase | pt_BR |
Subject in Portuguese | COVID-19 | pt_BR |
Subject in Portuguese | Exonuclease | pt_BR |
Subject in Portuguese | Potencial terapêutico | pt_BR |
Subject in Portuguese | Cultura de células virais | pt_BR |
Title | Combination of antiviral drugs inhibits SARS-CoV- 2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture | pt_BR |
Type | Article | pt_BR |
DOI | 10.1038/s42003-022-03101-9 | |
Abstract | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027, USA / Department of Chemistry, Columbia University, New York, NY 10027, USA. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | Laboratory of Structural Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. | pt_BR |
Affilliation | Laboratory of Structural Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. | pt_BR |
Affilliation | Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10065, USA. | pt_BR |
Affilliation | Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10065, USA. | pt_BR |
Affilliation | Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10065, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Subject | COVID-19 | pt_BR |
Subject | Combination of antiviral drugs | pt_BR |
Subject | Inhibits SARS-CoV-2 polymerase and exonuclease | pt_BR |
Subject | Therapeutic potential | pt_BR |
Subject | Viral cell culture | pt_BR |