Structure-based identification of potential SARS-CoV-2 main protease inhibitors

To address coronavirus disease (COVID-19), currently, no effective drug or vaccine is available. In this regard, molecular modeling approaches are highly useful to discover potential inhibitors of the main protease (M-pro) enzyme of SARS-CoV-2. Since, the M-pro enzyme plays key roles in mediating viral replication and transcription; therefore, it is considered as an attractive drug target to control SARS-CoV-2 infection. By using structure-based drug design, pharmacophore modeling, and virtual high throughput drug screening combined with docking and all-atom molecular dynamics simulation approach, we have identified five potential inhibitors of SARS-CoV-2 M-pro. MD simulation studies revealed that compound 54035018 binds to the M-pro with high affinity (Delta G (bind) -37.40 kcal/mol), and the complex is more stable in comparison with other protein-ligand complexes. We have identified promising leads to fight COVID-19 infection as these compounds fulfill all drug-likeness properties. However, experimental and clinical validations are required for COVID-19 therapy. Communicated by Ramaswamy H. Sarma

Automated summary

To address the lack of effective drugs or vaccines for COVID-19, researchers used molecular modeling methods to discover potential inhibitors of the SARS-CoV-2 M-pro enzyme. Through simulation studies, they identified five potential inhibitors, one of which showed high affinity and stability in binding to the M-pro. These compounds could be promising candidates for COVID-19 therapy, but further experimental and clinical validation is needed.