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Updated: Dec 16, 2025
Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
Published on: September 26, 2025
Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease
Emanuelle Machado Marinho1, João Batista de Andrade Neto2, Jacilene Silva3
1Department of Analytical Chemistry and Physical Chemistry, Group of Theoretical Chemistry (GQT), Science Center, Federal University of Ceará, Fortaleza, CE, 60.455-760, Brazil.
Abstract:
Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and that has now been declared a global pandemic by the World Health Organization. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In this context, this study aimed to evaluate in silico the molecular interactions of drugs with therapeutic indications for treatment of COVID-19 (Azithromycin, Baricitinib and Hydroxychloroquine) and drugs with similar structures (Chloroquine, Quinacrine and Ruxolitinib) in docking models from the SARS-CoV-2 main protease (M-pro) protein. The results showed that all inhibitors bound to the same enzyme site, more specifically in domain III of the SARS-CoV-2 main protease. Therefore, this study allows proposing the use of baricitinib and quinacrine, in combination with azithromycin; however, these computer simulations are just an initial step for conceiving new projects for the development of antiviral molecules.
Insights
This study used computer simulations to analyze drug interactions with the SARS-CoV-2 main protease. Researchers propose combining baricitinib and quinacrine with azithromycin for potential COVID-19 therapy.
Area of Science:
- Virology
- Computational Chemistry
- Pharmacology
Background:
- Coronavirus disease (COVID-19) is a global pandemic caused by an enveloped RNA virus.
- There is an urgent need for effective therapies and vaccines against COVID-19.
- The SARS-CoV-2 main protease (M-pro) is a key target for antiviral drug development.
Purpose of the Study:
- To evaluate the in silico molecular interactions of potential COVID-19 drugs with the SARS-CoV-2 main protease.
- To investigate drugs with existing therapeutic indications and structurally similar compounds.
- To identify promising drug candidates for further development against COVID-19.
Main Methods:
- Utilized molecular docking simulations to model drug-protein interactions.
- Focused on the SARS-CoV-2 main protease (M-pro) enzyme.
- Analyzed binding affinities and interaction sites of selected drugs.
Main Results:
- All tested inhibitors (Azithromycin, Baricitinib, Hydroxychloroquine, Chloroquine, Quinacrine, Ruxolitinib) bound to the same active site on the M-pro.
- The binding primarily occurred within domain III of the SARS-CoV-2 main protease.
- Baricitinib and Quinacrine showed potential for combined use with Azithromycin.
Conclusions:
- Computer simulations suggest potential synergistic effects of Baricitinib and Quinacrine with Azithromycin.
- These findings provide a basis for further experimental studies on novel antiviral drug development.
- In silico analysis is a valuable initial step in designing new therapeutic strategies against COVID-19.
