Computational and experimental approaches identify beta-blockers as potential SARS-CoV-2 spike inhibitors

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dc.creatorPuhl, Ana Cristina
dc.creatorSacramento, Carolina de Queiroz
dc.creatorTavella, Tatyana Almeida
dc.creatorDias, Gabriel Gonçalves
dc.creatorRodrigues, Natalia Fintelman
dc.creatorTemerozo, Jairo Ramos
dc.creatorDias, Suelen da Silva Gomes
dc.creatorRamos, Paulo Ricardo Pimenta da Silva
dc.creatorMerten, Eric M.
dc.creatorPearce, Kenneth H.
dc.creatorAndrade, Carolina Horta
dc.date.accessioned2024-11-19T13:01:22Z
dc.date.available2024-11-19T13:01:22Z
dc.date.issued2022
dc.description.abstractFinding 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-SARS-CoV-2 activity.
dc.identifier.citationPUHL, Ana Cristina et al. Computational and experimental approaches identify beta-blockers as potential SARS-CoV-2 spike inhibitors. ACS Omega, Washington, v. 7, n. 32, p. 27950-27958, 2022. DOI: 10.1021/acsomega.2c01707. Disponível em: https://pubs.acs.org/doi/10.1021/acsomega.2c01707. Acesso em: 21 out. 2024.
dc.identifier.doi10.1021/acsomega.2c01707
dc.identifier.issne- 2470-1343
dc.identifier.urihttps://pubs.acs.org/doi/10.1021/acsomega.2c01707
dc.identifier.urihttp://repositorio.bc.ufg.br//handle/ri/25919
dc.language.isoeng
dc.publisher.countryEstados unidos
dc.publisher.departmentFaculdade de Farmácia - FF (RMG)
dc.rightsAcesso Aberto
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAssays
dc.subjectCOVID-19
dc.subjectInfectious diseases
dc.subjectMolecular mechanics
dc.subjectSARS-CoV-2
dc.titleComputational and experimental approaches identify beta-blockers as potential SARS-CoV-2 spike inhibitors
dc.typeArtigo

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