ABSTRACT
Background. The outbreak of COVID-19 pandemic in China regarded as a major health/economic hazard. The importance of coming up with mechanisms for preventing or treating COVID-19 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. Methods. SIT-TAT nano-conjugates were prepared according to a full three-factor bi-level (23) factorial design. SIT concentration (mM, X1), TAT concentration (mM, X2), and pH (X3) were selected as the factors. Particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses. Characterization of the optimized formula for Fourier-transformed infrared (FTIR) and Transmission electron microscope was carried out. In addition, IC50 in Vero E6 cells, In vitro 3CL-protease inhibition and docking tests were investigated. 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 (IC50 = 3.959 μM ± 0.011) in comparison to isolated components (IC50 = 10.93 μM ± 0.25) and TAT (IC50 = 8.128 μM ± 0.42). 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). Conclusion. While offering significant binding interactions with protein's key pocket residues, an optimized formulation of SIT-TAT could guarantee both the enhanced delivery to the target cells and the improved cellular uptake. The presented findings would guarantee further investigations regarding formula optimization against SARS-CoV-2.
ABSTRACT
Background and Objective: The outbreak of the COVID-19 pandemic in China regarded as a major health/economic hazard. The importance of coming up with mechanisms for preventing or treating SARS-CoV-2 infection 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. Materials and Methods: Antiviral activity against SARS-CoV-2 propagated in Vero E6 cells, 3CL-protease inhibition activity and docking studies were examined. Eight formulae have been created using Design-Expert® Software to find the smallest complex size with the highest charge. The optimized formula was obtained then tested for antiviral activity. Results: 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 inhibitor effect (IC50 = 3.959±0.011 µM) in comparison to isolated components (IC50 = 10.93±0.25 µM) and TAT (IC50 = 8.128±0.42 µM). 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). Conclusion: SIT-TAT could guarantee an enhanced delivery to the target cells, improved cellular uptake and synergistic blockage of the target active site. Results of this study confirm the efficacy of the Sitagliptin HIV TAT complex in the suppression of SARS-CoV2 virus multiplication.