The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge The objective of the current work was to evaluate the efficacy of the combined complex of Sitagliptin (SIT) with melittin (MEL) against SARS-CoV-2 virus SIT-MEL nano-conjugates were optimized by a full three-factor bi-level (23) factorial design In addition, SIT concentration (mM, X1), MEL concentration (mM, X2), and pH (X3) were selected as the critical factors Particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses Characterization of the optimized formula for Fourier-transformed infrared (FTIR) was carried out The optimized formula showed particle size and zeta potential values of 77 42 nm and 27 67 mV, respectively When compared with SIT and MEL, the combination of SIT-MEL complex has shown anti-viral potential against isolate of SARS-CoV-2 with IC50 values of 8 439 muM with significant improvement (p &lt; 0 001) In addition, the complex showed IC50 in vitro 3CL-protease inhibition with IC50 7 216 microM Molecular docking has revealed that formula components have good predicted pocket accommodation of the SARS-CoV-2 3-CL protease An optimized formulation of SIT-MEL could guarantee both enhanced delivery to the target cells and the enhanced cellular uptake with promising activities against SARS-CoV-2
Repurposing of Sitagliptin- Melittin Optimized Nanoformula against SARS-CoV-2: Antiviral Screening and Molecular Docking Studies