A comparative study of 5-fluorouracil, doxorubicin, methotrexate, paclitaxel for their inhibition ability for Mpro of nCoV: Molecular docking and molecular dynamics simulations

The new corona virus (nCoV) is aetiological agent responsible for the viral pneumonia epidemic. Three is no specific therapeutic medicines available for the treatment of this condition and also effective treatment choices are few. In this work, authors tried to investigate few potential of repurposing drugs (5- fluorouracil, doxorubicin, methotrexate and paclitaxel) against the main protease (Mpro) of nCoV by the computational tools. Molecular docking was performed to screen out the best compound and doxorubicin was found to have minimum binding energy -121.89 kcal/mol. To further study, molecular dynamics (MD) simulations were performed at 300 K and the result successfully corroborate the energy obtained by molecular docking. Further, temperature dependent MD simulations of the best molecule, that is, doxorubicin based on results of docking, was performed to check the variation in structural changes in Mpro of nCoV at 290 K, 310 K, 320 K and 325 K. It is found that doxorubicin binds effectively with Mpro of nCoV at 290 K. Further, ADME properties of the 5- fluorouracil, doxorubicin, methotrexate and paclitaxel were also evaluated to understand the bioavailability.