Drug repurposing and computational modeling for discovery of inhibitors of the main protease (M<sup>pro</sup>) of SARS-CoV-2.
Silva. José Rogério A JRA; Kruger. Hendrik G HG; Molfetta. Fábio A FA
Key Findings
- Molecular docking predicts triptorelin binds SARS‑CoV‑2 main protease with strong free energy
- Darunavir also shows strong predicted binding
- The study identifies structural features that could guide new inhibitor design
Practical Outcomes
- The result is not ready for any self‑treatment or supplement protocol; it simply points to a hypothesis that needs lab experiments and safety testing before any real‑world use.
Summary
A computer study found that the hormone drug triptorelin might stick to a key COVID‑19 virus enzyme, suggesting it could possibly block the virus, but this is only a virtual prediction and hasn't been tested in labs or people.
Abstract
The main protease (M<sup>pro</sup> or 3CL<sup>pro</sup>) is a conserved cysteine protease from the coronaviruses and started to be considered an important drug target for developing antivirals, as it produced a deadly outbreak of COVID-19. Herein, we used a combination of drug reposition and computational modeling approaches including molecular docking, molecular dynamics (MD) simulations, and the calculated binding free energy to evaluate a set of drugs in complex with the M<sup>pro</sup> enzyme. Particularly, our results show that darunavir and triptorelin drugs have favorable binding free energy (-63.70 and -77.28 kcal mol<sup>-1</sup>, respectively) in complex with the M<sup>pro</sup> enzyme. Based on the results, the structural and energetic features that explain why some drugs can be repositioned to inhibit M<sup>pro</sup> from SARS-CoV-2 were exposed. These features should be considered for the design of novel M<sup>pro</sup> inhibitors.
Study Information
pubmed
2021
2021-07-02T00:00:00.000Z
10.1039/d1ra03956c
16
79