With cases of the new coronavirus disease 2019 (COVID-19) climbing steeply everywhere from Milan to Manhattan , overwhelming one hospital after another and pushing the global death toll past 49,000(2020-4-3), the sprint to find treatments has dramatically accelerated. Drugs that stop the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could save the lives of severely ill patients, protect health care workers and others at high risk of infection, and reduce the time patients spend in hospital beds.
As a world-renowned supplier of small molecular compounds, TargetMol performed a Swiss-Model Homology Modelling process to generate reliable protein models or 3D protein structures of Spike-RBD, ACE2, Mpro (3CLpro), PLpro, nsp16, X domain, and RdRp (nsp12). These protein models provide sufficient information for virtual screening against key proteins of SARS-CoV-2.
In the first round of Surflex-Dock virtual screening, to accelerate virtual screening, the maximum quantity of conformations was reduced from 20 to 10, the maximum quantity of rotatable bonds was decreased from 100 to 50, and the options for pre-dock minimization and post-dock minimization of molecules were omitted. The top 500 conformations were selected according to the docking score for the 2nd round of Surflex docking module screening, while reset the parameters as default. Finally, the top 100 conformations according to docking score were selected for manual screening.
Our last step is to apply manual screening to the top 100 compounds, where these compounds were extracted for further analyzing the interactions between ligand and active site such as hydrogen-bond, electrostatic attraction, hydrophobic effect, π-π stacking, and Cation-π Interaction, etc., and whether the structure of ligand has enough rigidity (especially for protein-protein interaction in RBD-ACE2 system, i.e. rotatable quantity of bonds).
Based on the above virtual screening results, and combined with the recent clinical reports, we have also obtained some valuable potential drugs for SARS-CoV-2, which can reduce drug development cycle by using drug relocation strategy.
COVID-19 has now been declared a pandemic and new treatments are urgently needed as we enter a phase beyond containment. Scientists are endeavoring to find antivirals specific to the virus. As an expert in drug screening, TargetMol would like to share the virtual screening results with scientists all of the world in drug discovery to fight against this novel coronavirus.