Design And Synthesis of Peptidomimetics for Antiviral Activity Against SARS-CoV-2

Abstract

The new world pandemic that is currently being caused by the SARS-CoV-2 also necessitates the formulation of potential effective antivirals within the shortest duration. The research performed was aimed at planning, synthesizing, and also testing new peptidomimetic molecules that could have the capability of inhibition in relation to SARS-CoV-2 main protease (M pro). By molecular modeling and docking, rationally designed peptidomimetics, 20 structurally diverse peptidomimetics were synthesized in solution phase and microwave condition. Biological purity and structural integrity of such compounds were completely established by the NMR, FTIR, LC-MS and HPLC. Vero E 6 cell line in screen of SARS-CoV-2 antiviral exhibited the activity of five compounds (P-02, P-04, P-06, P-07, and P-08) with the best activity and the most active compound P-07 was with IC 50 = 1.8 mM, SI >55. The analysis of the statistical significance done using ANOVA and TUKEY test indicated that P-07 was superior to the other candidates. It has been demonstrated in this work that peptidomimetics and, specifically, P-07, can serve as an anti-SARS-CoV-2 therapeutic agent and that a computational design and the validation of experimental studies can be important aspects of anticancer anti-viral drug development.