ABSTRACT
The outbreak of COVID-19 pandemic regarded as a major health/economic hazard. The importance of coming up with mechanisms for preventing or treating SARS-CoV-2infection has been felt across the world. This work aimed at examining the efficiency of Sitagliptin (SIT) and human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) against SARS-CoV-2 virus. 3CL-protease inhibition activity and docking studies were examined. According to the results, the prepared complex’s formula was as follows 1: 1 SIT: TAT molar ratio, whereas zeta potential and particle size values were at 34.17 mV and 97.19 nm, respectively. This combination did exhibit its antiviral potentiality against SARS-CoV-2 via IC50 values of 9.083 5.415, and 16.14 μM for TAT, SIT-TAT, and SIT, respectively. In addition, the complex SIT-TAT showed a significant (P < 0.001) viral-3CL-protease inhibitory effect. This was further confirmed via in silico study. Molecular docking investigation has shown promising binding affinity of the formula components towards SARS-CoV-2 main protease (3-CL).
ABSTRACT
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 µM with significant improvement (p < 0.001). In addition, the complex showed IC50 in vitro 3CL-protease inhibition with IC50 7.216 µM. 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.