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Updated: Nov 7, 2025
Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
Published on: September 26, 2025
A Study of 3CLpros as Promising Targets against SARS-CoV and SARS-CoV-2
Seri Jo1, Suwon Kim1, Jahyun Yoo1
1Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seoul 03760, Korea.
Abstract:
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), results in serious chaos all over the world. In addition to the available vaccines, the development of treatments to cure COVID-19 should be done quickly. One of the fastest strategies is to use a drug-repurposing approach. To provide COVID-19 patients with useful information about medicines currently being used in clinical trials, twenty-four compounds, including antiviral agents, were selected and assayed. These compounds were applied to verify the inhibitory activity for the protein function of 3CLpros (main proteases) of SARS-CoV and SARS-CoV-2. Among them, viral reverse-transcriptase inhibitors abacavir and tenofovir revealed a good inhibitory effect on both 3CLpros. Intriguingly, sildenafil, a cGMP-specific phosphodiesterase type 5 inhibitor also showed significant inhibitory function against them. The in silico docking study suggests that the active-site residues located in the S1 and S2 sites play key roles in the interactions with the inhibitors. The result indicates that 3CLpros are promising targets to cope with SAR-CoV-2 and its variants. The information can be helpful to design treatments to cure patients with COVID-19.
Insights
Drug repurposing identified potential COVID-19 treatments. Abacavir, tenofovir, and sildenafil showed inhibitory effects against SARS-CoV-2 main proteases, offering new therapeutic avenues for coronavirus disease 2019.
Area of Science:
- * Virology and Drug Discovery
- * Biochemistry and Molecular Biology
Background:
- * The global impact of coronavirus disease 2019 (COVID-19) necessitates rapid development of effective treatments.
- * Drug repurposing offers an accelerated strategy for identifying potential COVID-19 therapies.
Purpose of the Study:
- * To evaluate the inhibitory activity of selected compounds against SARS-CoV and SARS-CoV-2 main proteases (3CLpros).
- * To identify existing drugs that can be repurposed for COVID-19 treatment.
Main Methods:
- * Assay of twenty-four selected compounds for inhibitory activity against 3CLpros.
- * In silico molecular docking studies to analyze inhibitor-target interactions.
Main Results:
- * Viral reverse-transcriptase inhibitors abacavir and tenofovir demonstrated significant inhibition of both SARS-CoV and SARS-CoV-2 3CLpros.
- * Sildenafil, a phosphodiesterase type 5 inhibitor, also exhibited notable inhibitory effects.
- * In silico analysis indicated key roles for active-site residues in S1 and S2 sites in inhibitor binding.
Conclusions:
- * 3CLpros are validated as promising therapeutic targets for combating SARS-CoV-2 and its variants.
- * Abacavir, tenofovir, and sildenafil represent potential candidates for novel COVID-19 treatment strategies.
