Screening Anti-inflammatory, Anticoagulant, and Respiratory Agents for SARS-CoV-2 3CLpro Inhibition from Chemical Fingerprints Through a Deep Learning Approach.
Rev Invest Clin
; 74(1): 31-39, 2022 01 03.
Article
in English
| MEDLINE | ID: covidwho-1701042
ABSTRACT
BACKGROUND:
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiratory System Agents
/
Deep Learning
/
COVID-19 Drug Treatment
/
Anti-Inflammatory Agents
/
Anticoagulants
Type of study:
Etiology study
/
Experimental Studies
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Rev Invest Clin
Journal subject:
Medicine
Year:
2022
Document Type:
Article
Affiliation country:
Ric.21000282
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