Design and synthesis of novel phe-phe hydroxyethylene derivatives as potential coronavirus main protease inhibitors

Khorsandi, Zahra; Afshinpour, Maral; Molaei, Fatemeh; Askandar, Rafee Habib; Keshavarzipour, Fariba; Abbasi, Maryam; Sadeghi-Aliabadi, Hojjat

In response to the current pandemic caused by the novel SARS-CoV-2, we design new compounds based on Lopinavir structure as an FDA-approved antiviral agent which is currently under more evaluation in clinical trials for COVID-19 patients. This is the first example of the preparation of Lopinavir isosteres from the main core of Lopinavir conducted to various heterocyclic fragments. It is proposed that main protease inhibitors play an important role in the cycle life of coronavirus. Thus, the protease inhibition effect of synthesized compounds was studied by molecular docking method. All of these 10 molecules, showing a good docking score compared. Molecular dynamics (MD) simulations also confirmed the stability of the best-designed compound in Mpro active site. Communicated by Ramaswamy H. Sarma