tetano
Editor, Senior Moderator
Pharmaceuticals (Basel)
. 2021 Feb 24;14(3):178.
doi: 10.3390/ph14030178.
Evaluation of the Antiviral Activity of Sitagliptin-Glatiramer Acetate Nano-Conjugates against SARS-CoV-2 Virus
Nabil A Alhakamy[SUP] 1 2 3 4 [/SUP], Osama A A Ahmed[SUP] 1 2 3 [/SUP], Tarek S Ibrahim[SUP] 5 [/SUP], Hibah M Aldawsari[SUP] 1 2 3 [/SUP], Khalid Eljaaly[SUP] 6 7 [/SUP], Usama A Fahmy[SUP] 1 2 [/SUP], Ahmed L Alaofi[SUP] 8 [/SUP], Filippo Caraci[SUP] 9 10 [/SUP], Giuseppe Caruso[SUP] 9 [/SUP]
Affiliations
Abstract
The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. There is a current race for developing strategies to treat and/or prevent COVID-19 worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes COVID-19. The aim of the present work was to evaluate the efficacy of the combined complex (nano-conjugates) of two FDA-approved drugs, sitagliptin (SIT) and glatiramer acetate (GA), against a human isolate of the SARS-CoV-2 virus. SIT-GA nano-conjugates were prepared according to a full three-factor bilevel (2[SUP]3[/SUP]) factorial design. The SIT concentration (mM, X[SUB]1[/SUB]), GA concentration (mM, X[SUB]2[/SUB]), and pH (X[SUB]3[/SUB]) were selected as the factors. The particle size (nm, Y[SUB]1[/SUB]) and zeta potential (mV, Y[SUB]2[/SUB]) were assessed as responses. Characterization of the optimized formula for the Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) was carried out. In addition, the half-maximal inhibitory concentration (IC[SUB]50[/SUB]) in Vero-E6 epithelial cells previously infected with the virus was investigated. The results revealed that the optimized formula of the prepared complex was a 1:1 SIT:GA molar ratio at a pH of 10, which met the required criteria with a desirability value of 0.878 and had a particle size and zeta potential at values of 77.42 nm and 27.67 V, respectively. The SIT-GA nano-complex showed antiviral potential against an isolate of SARS-CoV-2 with IC50 values of 16.14, 14.09, and 8.52 ?M for SIT, GA, and SIT-GA nano-conjugates, respectively. Molecular docking has shown that the formula's components have a high binding affinity to the COVID 3CL protease, essential for coronavirus replication, paralleled by 3CL protease inhibition (IC[SUB]50[/SUB] = 2.87 ?M). An optimized formulation of SIT-GA could guarantee both enhanced deliveries to target cells and improved cellular uptake. Further clinical studies are being carried out to validate the clinical efficacy of the optimized formulation against SARS-CoV-2.
Keywords: 3CL protease; COVID-19; SARS-CoV-2; glatiramer acetate; nanoparticles; sitagliptin.
. 2021 Feb 24;14(3):178.
doi: 10.3390/ph14030178.
Evaluation of the Antiviral Activity of Sitagliptin-Glatiramer Acetate Nano-Conjugates against SARS-CoV-2 Virus
Nabil A Alhakamy[SUP] 1 2 3 4 [/SUP], Osama A A Ahmed[SUP] 1 2 3 [/SUP], Tarek S Ibrahim[SUP] 5 [/SUP], Hibah M Aldawsari[SUP] 1 2 3 [/SUP], Khalid Eljaaly[SUP] 6 7 [/SUP], Usama A Fahmy[SUP] 1 2 [/SUP], Ahmed L Alaofi[SUP] 8 [/SUP], Filippo Caraci[SUP] 9 10 [/SUP], Giuseppe Caruso[SUP] 9 [/SUP]
Affiliations
- PMID: 33668390
- DOI: 10.3390/ph14030178
Abstract
The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. There is a current race for developing strategies to treat and/or prevent COVID-19 worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes COVID-19. The aim of the present work was to evaluate the efficacy of the combined complex (nano-conjugates) of two FDA-approved drugs, sitagliptin (SIT) and glatiramer acetate (GA), against a human isolate of the SARS-CoV-2 virus. SIT-GA nano-conjugates were prepared according to a full three-factor bilevel (2[SUP]3[/SUP]) factorial design. The SIT concentration (mM, X[SUB]1[/SUB]), GA concentration (mM, X[SUB]2[/SUB]), and pH (X[SUB]3[/SUB]) were selected as the factors. The particle size (nm, Y[SUB]1[/SUB]) and zeta potential (mV, Y[SUB]2[/SUB]) were assessed as responses. Characterization of the optimized formula for the Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) was carried out. In addition, the half-maximal inhibitory concentration (IC[SUB]50[/SUB]) in Vero-E6 epithelial cells previously infected with the virus was investigated. The results revealed that the optimized formula of the prepared complex was a 1:1 SIT:GA molar ratio at a pH of 10, which met the required criteria with a desirability value of 0.878 and had a particle size and zeta potential at values of 77.42 nm and 27.67 V, respectively. The SIT-GA nano-complex showed antiviral potential against an isolate of SARS-CoV-2 with IC50 values of 16.14, 14.09, and 8.52 ?M for SIT, GA, and SIT-GA nano-conjugates, respectively. Molecular docking has shown that the formula's components have a high binding affinity to the COVID 3CL protease, essential for coronavirus replication, paralleled by 3CL protease inhibition (IC[SUB]50[/SUB] = 2.87 ?M). An optimized formulation of SIT-GA could guarantee both enhanced deliveries to target cells and improved cellular uptake. Further clinical studies are being carried out to validate the clinical efficacy of the optimized formulation against SARS-CoV-2.
Keywords: 3CL protease; COVID-19; SARS-CoV-2; glatiramer acetate; nanoparticles; sitagliptin.