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Computational Insights on the Potential of Some NSAIDs for Treating COVID-19: Priority Set and Lead Optimization
- Source :
- Molecules, Volume 26, Issue 12, Molecules, Vol 26, Iss 3772, p 3772 (2021)
- Publication Year :
- 2021
-
Abstract
- The discovery of drugs capable of inhibiting SARS-CoV-2 is a priority for human beings due to the severity of the global health pandemic caused by COVID-19. To this end, repurposing of FDA-approved drugs such as NSAIDs against COVID-19 can provide therapeutic alternatives that could be utilized as an effective safe treatment for COVID-19. The anti-inflammatory activity of NSAIDs is also advantageous in the treatment of COVID-19, as it was found that SARS-CoV-2 is responsible for provoking inflammatory cytokine storms resulting in lung damage. In this study, 40 FDA-approved NSAIDs were evaluated through molecular docking against the main protease of SARS-CoV-2. Among the tested compounds, sulfinpyrazone 2, indomethacin 3, and auranofin 4 were proposed as potential antagonists of COVID-19 main protease. Molecular dynamics simulations were also carried out for the most promising members of the screened NSAID candidates (2, 3, and 4) to unravel the dynamic properties of NSAIDs at the target receptor. The conducted quantum mechanical study revealed that the hybrid functional B3PW91 provides a good description of the spatial parameters of auranofin 4. Interestingly, a promising structure–activity relationship (SAR) was concluded from our study that could help in the future design of potential SARS-CoV-2 main protease inhibitors with expected anti-inflammatory effects as well. NSAIDs may be used by medicinal chemists as lead compounds for the development of potent SARS-CoV-2 (Mpro) inhibitors. In addition, some NSAIDs can be selectively designated for treatment of inflammation resulting from COVID-19.
- Subjects :
- Models, Molecular
medicine.medical_treatment
Indomethacin
Pharmaceutical Science
Pharmacology
DFT calculations
Ligands
01 natural sciences
Analytical Chemistry
QD241-441
Drug Discovery
skin and connective tissue diseases
Repurposing
Coronavirus 3C Proteases
0303 health sciences
drug repurposing
Anti-Inflammatory Agents, Non-Steroidal
Sulfinpyrazone
Molecular Docking Simulation
Drug repositioning
Cytokine release syndrome
Chemistry (miscellaneous)
docking
Molecular Medicine
Cytokine Release Syndrome
medicine.drug
Protein Binding
Auranofin
Molecular Dynamics Simulation
Antiviral Agents
Article
SARS-CoV-2 main protease
03 medical and health sciences
Structure-Activity Relationship
medicine
Structure–activity relationship
Humans
Protease Inhibitors
Physical and Theoretical Chemistry
030304 developmental biology
Protease
Binding Sites
010405 organic chemistry
business.industry
SARS-CoV-2
United States Food and Drug Administration
Organic Chemistry
Drug Repositioning
COVID-19
Computational Biology
medicine.disease
molecular dynamics
United States
0104 chemical sciences
COVID-19 Drug Treatment
Docking (molecular)
business
Databases, Chemical
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Molecules (Basel, Switzerland)
- Accession number :
- edsair.doi.dedup.....c19298a156df163f4ac75316b532c0b2