Upgrading nirmatrelvir to inhibit SARS-CoV-2 Mpro via DeepFrag and free energy calculations

Chúng tôi vui mừng thông báo rằng TS. Ngô Sơn Tùng và các đồng nghiệp gần đây đã xuất bản công trình của họ có tựa đề "Upgrading nirmatrelvir to inhibit SARS-CoV-2 Mpro via DeepFrag and free energy calculations" trên tạp chí Journal of Molecular Graphics and Modelling.

Tóm tắt:

The first oral drug for the treatment of COVID-19, Paxlovid, has been authorized; however, nirmatrelvir, a major component of the drug, is reported to be associated with some side effects. Moreover, the appearance of many novel variants raises concerns about drug resistance, and designing new potent inhibitors to prevent viral replication is thus urgent. In this context, using a hybrid approach combining machine learning (ML) and free energy simulations, 6 compounds obtained by modifying nirmatrelvir were proposed to bind strongly to SARS-CoV-2 Mpro. The structural modification of nirmatrelvir significantly enhances the electrostatic interaction free energy between the protein and ligand and slightly decreases the vdW term. However, the vdW term is the most important factor in controlling the ligand-binding affinity. In addition, the modified nirmatrelvir might be less toxic to the human body than the original inhibitor.