The repurposed drugs suramin and quinacrine cooperatively inhibit sars-cov-2 3clpro in vitro

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorForschungszentrum Jülich-
Autor(es): dc.contributorHeinrich-Heine-Universität Düsseldorf-
Autor(es): dc.contributorFederal University of Tocantins-
Autor(es): dc.contributorFederal University of Mato Grosso do Sul-
Autor(es): dc.contributorForchungszentrum Jülich-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.creatorEberle, Raphael J.-
Autor(es): dc.creatorOlivier, Danilo S.-
Autor(es): dc.creatorAmaral, Marcos S.-
Autor(es): dc.creatorGering, Ian-
Autor(es): dc.creatorWillbold, Dieter-
Autor(es): dc.creatorArni, Raghuvir K. [UNESP]-
Autor(es): dc.creatorCoronado, Monika A. [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:47:04Z-
Data de disponibilização: dc.date.available2022-02-22T00:47:04Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2020-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/v13050873-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/206432-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/206432-
Descrição: dc.descriptionSince the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro ). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro . We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.-
Descrição: dc.descriptionUniversidade Federal de Mato Grosso do Sul-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionFundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionInstitute of Biological Information Processing (IBI-7 Structural Biochemistry) Forschungszentrum Jülich-
Descrição: dc.descriptionInstitut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf, Universitätsstraße-
Descrição: dc.descriptionCampus Cimba Federal University of Tocantins-
Descrição: dc.descriptionInstitute of Physics Federal University of Mato Grosso do Sul-
Descrição: dc.descriptionJuStruct: Jülich Centre for Structural Biology Forchungszentrum Jülich-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation IBILCE Universidade Estadual Paulista (UNESP)-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation IBILCE Universidade Estadual Paulista (UNESP)-
Descrição: dc.descriptionFAPESP: 2016/12904-0-
Descrição: dc.descriptionFAPESP: 2018/07572-3-
Descrição: dc.descriptionFAPESP: 2018/12659-0-
Descrição: dc.descriptionFAPESP: 2019/05614-3-
Descrição: dc.descriptionFundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul: 23/200.307/2014-
Descrição: dc.descriptionCNPq: 307338/2014-2-
Descrição: dc.descriptionCNPq: 401270/2014-9-
Descrição: dc.descriptionCNPq: 435913/2016-6-
Idioma: dc.languageen-
Relação: dc.relationViruses-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject3CLpro-
Palavras-chave: dc.subjectCOVID-19-
Palavras-chave: dc.subjectMain protease-
Palavras-chave: dc.subjectQuinacrine-
Palavras-chave: dc.subjectRepurposing approved drugs-
Palavras-chave: dc.subjectSARS-CoV-2-
Palavras-chave: dc.subjectSuramin-
Título: dc.titleThe repurposed drugs suramin and quinacrine cooperatively inhibit sars-cov-2 3clpro in vitro-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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