Drug repurposing for viral variants may prove to be an efficient means to combat the mutating of COVID-19. As vaccine-resistant variants emerge, many patients with comorbidities require hospitalization due to sever complications. The fastest and cheapest route to discovering a new treatment is to check if any of the existing approved drugs are effective against COVID.
The search begins…
Recently, the FDA-approved drugs library was used for this purpose. To begin, first a simulation of each drug molecule docking with SARS-CoV-2 spike receptor-binding domain was run. The database contained around 2,500 drugs.
The spike receptor-binding domain was chosen for the simulation because it is already known that this domain plays a significant role in the entry of the virus into the host cell. The primary goal of this study is to find a drug that can impede the entry point, and thereby prevent infection from even beginning.
From the library of 2,500 drugs, 20 showed good results with the simulation and relatively high safety profiles. These 20 were carried on for further validation in the lab using a binding assay kit. The assay kit was also specific for the SARS-CoV-2 spike binding.
From the binding assay, 5 of the molecules continued to show promise as they consistently and significantly inhibit the binding of SARS-CoV-2 and the receptor. These 5 were carried on with in vitro work using Vero E6 cells. Each molecule was assessed for the required concentration and toxic concentration.
And then there were 3…
From the 5 molecules, 3 of them continued to show promise against SARS-CoV-2. These 3: argatroban, ranolazine, and glimepiride had a high selectivity index, and most interestingly, they each impacted different stages of the viral life cycle. Argatroban induced a direct virucidal effect; glimepiride inhibited viral replication; ranolazine inhibited viral adsorption onto the host cell.
This project has successfully identified 3 high-potential candidates for drug repurposing by weeding through the library of 2,500 already approved drugs. Further testing must also be done to develop the most safe and effective dosing, formulation, and potentially combination therapies to continue combating the new COVID variants.
Sobky S, Fawzy I, Ahmed M, et al. Drug repurposing of argatroban, glimepiride, and ranolazine shows anti-SARS-CoV-2 activity via diverse mechanisms. Heliyon. 2025 Jan 10;11(3):e41894. PMID: 39968139