Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/55211 |
Resumo: | Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina 27606, United States. |
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Phul, Ana C.Mottin, MelinaSacramento, Carolina Q.Tavella, Tatyana AlmeidaDias, Gabriel GonçalvesFintelman-Rodrigues, NataliaTemerozo, Jairo R.Dias, Suelen S. G.Ramos, Paulo Ricardo Pimenta da SilvaMerten, Eric M.Pearce, Kenneth H.Costa, Fabio Trindade MaranhãoPremkumar, LakshmananeSouza, Thiago Moreno L.Andrade, Carolina HortaEkins, Sean2022-10-20T17:56:44Z2022-10-20T17:56:44Z2022PUHL, Ana C. et al. Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors. ACS Omega, n.7, p. 27950-27958, 2022.2470-1343https://www.arca.fiocruz.br/handle/icict/5521110.1021/acsomega.2c01707engAmerican Chemical SocietyAbordagens Computacionais e ExperimentaisIdentificam Beta-BloqueadoresPotenciais inibidores de pico de SARS-CoV-2Computational and Experimental ApproachesIdentify Beta-BlockersPotential SARS-CoV‑2 Spike InhibitorsComputational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitorsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCollaborations Pharmaceuticals, Inc., Raleigh, North Carolina 27606, United States.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design de Medicamentos. Goiânia, GO, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia/ Centro de Desenvolvimento Tecnológico de Saúde / Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.Universidade de Campinas. Departamento de Genética, Evolução, Microbiologia e Imunologia. Laboratório de Doenças Tropicais. Campinas, SP, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Molecular Modelagem e Design de Medicamentos. Goiânia, GO. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia / Centro de Desenvolvimento Tecnológico de Saúde / Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. LabMol - Laboratório de Modelagem Molecular e Design de Fármacos. Goiânia, GO, Brasil.Center for Integrative Chemical Biology and Drug Discovery, Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.Center for Integrative Chemical Biology and Drug Discovery, Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27599, United StatesUniversidade de Campinas. Departamento de Genética, Evolução, Microbiologia e Imunologia. Laboratório de Doenças Tropicais Prof. Dr. Luiz Jacinto da Silva. Campinas, SP, Brasil.Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, United States.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia / Centro de Desenvolvimento Tecnológico de Saúde / Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças da População Negligenciadas. Rio de Janeiro, RJ, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design de Fármacos. Goiânia, GO, Brasil.Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina 27606, United States.Finding antivirals for SARS-CoV-2 is still a major challenge, and many computational and experimental approaches have been employed to find a solution to this problem. While the global vaccination campaigns are the primary driver of controlling the current pandemic, orally bioavailable small-molecule drugs and biologics are critical to overcome this global issue. Improved therapeutics and prophylactics are required to treat people with circulating and emerging new variants, addressing severe infection, and people with underlying or immunocompromised conditions. The SARS-CoV-2 envelope spike is a challenging target for viral entry inhibitors. Pindolol presented a good docking score in a previous virtual screening using computational docking calculations after screening a Food and Drug Administration (FDA)-approved drug library of 2400 molecules as potential candidates to block the SARS-CoV-2 spike protein interaction with the angiotensin-converting enzyme 2 (ACE-2). Here, we expanded the computational evaluation to identify five beta-blockers against SARS-CoV-2 using several techniques, such as microscale thermophoresis, NanoDSF, and in vitro assays in different cell lines. These data identified carvedilol with a Kd of 364 ± 22 nM for the SARS-CoV-2 spike and in vitro activity (EC50 of 7.57 μM, CC50 of 18.07 μM) against SARS-CoV-2 in Calu-3 cells. We have shown how we can apply multiple computational and experimental approaches to find molecules that can be further optimized to improve anti-SARSCoV- 2 activity.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALThiagoMSouza_NataliaRodrigues_etal_IOC_2022.pdfThiagoMSouza_NataliaRodrigues_etal_IOC_2022.pdfapplication/pdf3898095https://www.arca.fiocruz.br/bitstream/icict/55211/2/ThiagoMSouza_NataliaRodrigues_etal_IOC_2022.pdffdf71c443e6d4ba30dd875e04c9b5f62MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/55211/3/license.txt5a560609d32a3863062d77ff32785d58MD53icict/552112023-09-14 15:46:29.592oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-14T18:46:29Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors |
| title |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors |
| spellingShingle |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors Phul, Ana C. Abordagens Computacionais e Experimentais Identificam Beta-Bloqueadores Potenciais inibidores de pico de SARS-CoV-2 Computational and Experimental Approaches Identify Beta-Blockers Potential SARS-CoV‑2 Spike Inhibitors |
| title_short |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors |
| title_full |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors |
| title_fullStr |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors |
| title_full_unstemmed |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors |
| title_sort |
Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors |
| author |
Phul, Ana C. |
| author_facet |
Phul, Ana C. Mottin, Melina Sacramento, Carolina Q. Tavella, Tatyana Almeida Dias, Gabriel Gonçalves Fintelman-Rodrigues, Natalia Temerozo, Jairo R. Dias, Suelen S. G. Ramos, Paulo Ricardo Pimenta da Silva Merten, Eric M. Pearce, Kenneth H. Costa, Fabio Trindade Maranhão Premkumar, Lakshmanane Souza, Thiago Moreno L. Andrade, Carolina Horta Ekins, Sean |
| author_role |
author |
| author2 |
Mottin, Melina Sacramento, Carolina Q. Tavella, Tatyana Almeida Dias, Gabriel Gonçalves Fintelman-Rodrigues, Natalia Temerozo, Jairo R. Dias, Suelen S. G. Ramos, Paulo Ricardo Pimenta da Silva Merten, Eric M. Pearce, Kenneth H. Costa, Fabio Trindade Maranhão Premkumar, Lakshmanane Souza, Thiago Moreno L. Andrade, Carolina Horta Ekins, Sean |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Phul, Ana C. Mottin, Melina Sacramento, Carolina Q. Tavella, Tatyana Almeida Dias, Gabriel Gonçalves Fintelman-Rodrigues, Natalia Temerozo, Jairo R. Dias, Suelen S. G. Ramos, Paulo Ricardo Pimenta da Silva Merten, Eric M. Pearce, Kenneth H. Costa, Fabio Trindade Maranhão Premkumar, Lakshmanane Souza, Thiago Moreno L. Andrade, Carolina Horta Ekins, Sean |
| dc.subject.other.en_US.fl_str_mv |
Abordagens Computacionais e Experimentais Identificam Beta-Bloqueadores Potenciais inibidores de pico de SARS-CoV-2 |
| topic |
Abordagens Computacionais e Experimentais Identificam Beta-Bloqueadores Potenciais inibidores de pico de SARS-CoV-2 Computational and Experimental Approaches Identify Beta-Blockers Potential SARS-CoV‑2 Spike Inhibitors |
| dc.subject.en.en_US.fl_str_mv |
Computational and Experimental Approaches Identify Beta-Blockers Potential SARS-CoV‑2 Spike Inhibitors |
| description |
Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina 27606, United States. |
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2022 |
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2022-10-20T17:56:44Z |
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2022-10-20T17:56:44Z |
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2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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PUHL, Ana C. et al. Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors. ACS Omega, n.7, p. 27950-27958, 2022. |
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https://www.arca.fiocruz.br/handle/icict/55211 |
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2470-1343 |
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10.1021/acsomega.2c01707 |
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PUHL, Ana C. et al. Computational and Experimental Approaches Identify Beta-Blockers as Potential SARS-CoV‑2 Spike Inhibitors. ACS Omega, n.7, p. 27950-27958, 2022. 2470-1343 10.1021/acsomega.2c01707 |
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American Chemical Society |
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American Chemical Society |
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