Virtual screening: searching for future drugs

Now, the clinical approach of COVID-19 is based on the symptomatic treatments through anti-inflammatory agents (for instance, dexamethasone or cytokine inhibitors) combined with antibiotics to treat secondary infections. Recently, the antiviral ritonavir has been approved, but there is still a need for new medicines. Within the context of global health, it is urgent to develop SARS-CoV-2-specific antiviral therapeutics and this led to the application of several strategies to identify bioactive compounds that can be used as therapeutic agents (including the available drugs and natural products). In this context, the virtual screening is a reliable, fast and efficient procedure for finding bioactive compounds of large chemical collections against a specific molecular target.

As part of the study, the team conducted a virtual screening of the natural product database Selleck —a chemical library with nearly 2,000 compounds— for a series of conformations of the SARS-CoV-2 Mpro characterized with a molecular dynamics study.

As a result, the study presents the characterization of the dynamic profile of Mpro protease in its apo shape through conventional simulations (cMD) and Gaussian accelerated molecular dynamics (GaMD) simulations, and it defines a series of representative structures.

These structures were later used to carry out the ensemble docking, a bioinformatic method that enables the prediction and calculation using computational techniques of the most favourable position of interaction between a ligand and its target protein. Then, they carried out an iterative procedure which increased the length of cMD of protein-ligand complexes and calculated the free binding energy to select the most promising candidates.