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

ABSTRACT: 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 (ΔG _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.

SUBMITTER: Khan S 

PROVIDER: S-EPMC7682383 | biostudies-literature |

REPOSITORIES: biostudies-literature