Evaluation of the Antiviral Activity of Sitagliptin-Glatiramer Acetate Nano-Conjugates against SARS-CoV-2 Virus

Nabil A Alhakamy; Osama A A Ahmed; Tarek S Ibrahim; Hibah M Aldawsari; Khalid Eljaaly; Usama A Fahmy; Ahmed L Alaofi; Filippo Caraci; Giuseppe Caruso

doi:10.3390/ph14030178

Evaluation of the Antiviral Activity of Sitagliptin-Glatiramer Acetate Nano-Conjugates against SARS-CoV-2 Virus

Pharmaceuticals (Basel). 2021 Feb 24;14(3):178. doi: 10.3390/ph14030178.

Authors

Nabil A Alhakamy^{1

2

3

4}, Osama A A Ahmed^{1

2

3}, Tarek S Ibrahim⁵, Hibah M Aldawsari^{1

2

3}, Khalid Eljaaly^{6

7}, Usama A Fahmy^{1

2}, Ahmed L Alaofi⁸, Filippo Caraci^{9

10}, Giuseppe Caruso⁹

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
³ Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁴ King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Organic chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁷ Pharmacy Practice and Science Department, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
⁸ Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
⁹ Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.
¹⁰ Oasi Research Institute-IRCCS, 94018 Troina, Italy.

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 (2³) factorial design. The SIT concentration (mM, X₁), GA concentration (mM, X₂), and pH (X₃) were selected as the factors. The particle size (nm, Y₁) and zeta potential (mV, Y₂) 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 (IC₅₀) 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 µM 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 (IC₅₀ = 2.87 µM). 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.

Grants and funding

GCV19-21-1441/Deanship of Scientific Research (D.S.R.), King Abdulaziz University