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In silico studies of Mpro and PLpro from SARS-CoV-2 and a new class of cephalosporin drugs containing 1,2,4-thiadiazole.
Delgado, Cássia Pereira; Rocha, João Batista Teixeira; Orian, Laura; Bortoli, Marco; Nogara, Pablo Andrei.
  • Delgado CP; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS 97105-900 Brazil.
  • Rocha JBT; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS 97105-900 Brazil.
  • Orian L; Dipartimento di Scuenze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131 Padua, Italy.
  • Bortoli M; Institut de Química Computacionali Catàlisi (IQCC), Departament de Química, Facultat de Ciències, Universitat de Girona, C/M. A. Capmany 69, 17003 Girona, Spain.
  • Nogara PA; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS 97105-900 Brazil.
Struct Chem ; 33(6): 2205-2220, 2022.
Article in English | MEDLINE | ID: covidwho-2014356
ABSTRACT
The SARS-CoV-2 proteases Mpro and PLpro are important targets for the development of antivirals against COVID-19. The functional group 1,2,4-thiadiazole has been indicated to inhibit cysteinyl proteases, such as papain and cathepsins. Of note, the 1,2,4-thiadiazole moiety is found in a new class of cephalosporin FDA-approved antibiotics ceftaroline fosamil, ceftobiprole, and ceftobiprole medocaril. Here we investigated the interaction of these new antibiotics and their main metabolites with the SARS-CoV-2 proteases by molecular docking, molecular dynamics (MD), and density functional theory (DFT) calculations. Our results indicated the PLpro enzyme as a better in silico target for the new antibacterial cephalosporins. The results with ceftaroline fosamil and the dephosphorylate metabolite compounds should be tested as potential inhibitor of PLpro, Mpro, and SARS-CoV-2 replication in vitro. In addition, the data here reported can help in the design of new potential drugs against COVID-19 by exploiting the S atom reactivity in the 1,2,4-thiadiazole moiety. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-02036-5.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Struct Chem Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Struct Chem Year: 2022 Document Type: Article