Therapeutic switching of metronidazole anti-cancerous compounds as anti SARS-COV-2 inhibitors: integration of QSAR, molecular docking, MD simulation and ADMET analysis

The global economy and public health are seriously at risk because of the COVID-19 outbreak brought on by the SARS-CoV-2. Currently, there is no specific medication available to treat COVID-19 patients. A quick method used to find out the treatment of newly developing infectious diseases like SARS COV-2 by drug repurposing. Metronidazole (3-methyl-5-nitroimidazole) is a synthetic, azomycin derivative having strong bacteriocidal and antiparasitic properties. Metronidazole (MTZ) derivatives are commercially broad spectrum containing pertinent antibacterial activity and a reasonable safety profile. MTZ structures were designed using chemdraw professional and subjected to field base and atom base QSAR and displayed good results by identifying 9 compounds as active. Molecular docking was performed with 9 proteins from which highest docking score was ranged from − 6.305 to − 8.044 of MT35 with 7aot as compared to standard drug (Lopinavir, showed docking score − 5.504 with same protein). Docking was further validated by redocking by RMSD score in range of 2 Å. MMGB/SA results showed the negative binding energy values of docked protein–ligand complexes comparable to standard drug and MD stimulation were also performed for the structure flexibility showed 1.00 Å RMSF for three protein at maximum fluctuation. Selected drug (MT35) showed good ADME properties which may need to be synthesized followed by in vitro and in vivo study against SARS-CoV-2. Graphical Abstract