Programme

P.56 -- Poster, VCTP-47

Date: Thursday, 4 August 2022

Time: 08:30 - 10:00

Investigating the structural features of SRAS-CoV-2 Mpro binding site bound covalent ligands at physiological temperature

Hien T. T. Lai, Agata Kranjc, Toan T. Nguyen

Key Laboratory for Multiscale Simulation of Complex Systems, and Department of Theoretical Physics, University of Science, Vietnam National University – Hanoi 334 Nguyen Trai street, Thanh Xuan, Hanoi, Vietnam

The SARS-CoV-2 pandemic was firstly detected at the end of December 2019 in China, and quickly spread around the world, has been heavy threating global health. Although various COVID-19 vaccines and drugs are approved, developing antiviral drugs and vaccines against COVID-19 virus with high effectiveness is a long-term measure. The SARS-CoV-2 Mpro protein plays important roles in replication and transcription to this viral cycle life, together with three other targets for developing potential drugs treatment to COVID-19 patients. In this research, we investigate the SARS-CoV-2 Mpro binding site bound covalent ligands, 11a and 11b at physiology temperature (310K) using all-atom simulations, then compare to their X-ray experimental structures (at 273K) for understanding the thermodynamic features. We found that conformations of both Mpro proteins and covalent ligands are stable during 500ns of the simulation time. The ligand 11b are more flexible conformation than ligand 11a, meaning that both of them are potential leader compounds for binding to Mpro binding site against SARS-CoV-2, and the covalent ligand 11a has higher binding affinity, as their experiment reported. In addition, the configures of side chains, specially, the catalytic residue H41 and E166, located in the binding sites of Mpro protein are changed a bit in our simulations for easier binding to the ligands and stable structure, while these thermodynamics features are not found in experimental structures. These results are a root for developing candidate drugs against SARS-CoV-2 and other viral strains in the future.

Presenter: Nguyễn Thế Toàn