Screening Anti-inflammatory, Anticoagulant, and Respiratory Agents for SARS-CoV-2 3CLpro Inhibition from Chemical Fingerprints Through a Deep Learning Approach



Título del documento: Screening Anti-inflammatory, Anticoagulant, and Respiratory Agents for SARS-CoV-2 3CLpro Inhibition from Chemical Fingerprints Through a Deep Learning Approach
Revista: Revista de investigación clínica
Base de datos: PERIÓDICA
Número de sistema: 000452987
ISSN: 0034-8376
Autores: 1
Instituciones: 1Universidade Federal da Bahia, Instituto Multidisciplinar em Saude, Vitoria da Conquista, Bahia. Brasil
Año:
Periodo: Ene-Feb
Volumen: 74
Número: 1
Paginación: 31-39
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Aplicado, descriptivo
Resumen en inglés Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), triggers a pathophysiological process linked not only to viral mechanisms of infectivity, but also to the pattern of host response. Drug repurposing is a promising strategy for rapid identification of treatments for SARS-CoV-2 infection, and several attractive molecular viral targets can be exploited. Among those, 3CL protease is a potential target of great interest. Objective: The objective of the study was to screen potential 3CLpro inhibitors compounds based on chemical fingerprints among anti-inflammatory, anticoagulant, and respiratory system agents. Methods: The screening was developed based on a drug property prediction framework, in which the evaluated property was the ability to inhibit the activity of the 3CLpro protein, and the predictions were performed using a dense neural network trained and validated on bioassay data. Results: On the validation and test set, the model obtained area under the curve values of 98.2 and 76.3, respectively, demonstrating high specificity for both sets (98.5% and 94.7%). Regarding the 1278 compounds screened, the model indicated four anti-inflammatory agents, two anticoagulants, and one respiratory agent as potential 3CLpro inhibitors. Conclusions: Those findings point to a possible desirable synergistic effect in the management of patients with COVID-19 and provide potential directions for in vitro and in vivo research, which are indispensable for the validation of their results
Disciplinas: Medicina
Palabras clave: Farmacología,
Fisiopatología,
COVID-19,
SARS-CoV-2,
Antiinflamatorios,
Anticoagulantes,
Proteasas virales
Keyword: Pharmacology,
Physiopathology,
COVID-19,
SARS-CoV-2,
Antiinflammatory agents,
Anticoagulants,
Viral proteases
Texto completo: Texto completo (Ver HTML) Texto completo (Ver PDF)