Integrating State-Space Modeling, Parameter Estimation, Deep Learning, and Docking Techniques in Drug Repurposing: A Case Study on COVID-19 Cytokine Storm.
IF 4.7 2区 医学Q1 COMPUTER SCIENCE, INFORMATION SYSTEMS
Abhisek Bakshi, Kaustav Gangopadhyay, Sujit Basak, Rajat K De, Souvik Sengupta, Abhijit Dasgupta
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引用次数: 0
Abstract
Objective: This study addresses the significant challenges posed by emerging SARS-CoV-2 variants, particularly in developing diagnostics and therapeutics. Drug repurposing is investigated by identifying critical regulatory proteins impacted by the virus, providing rapid and effective therapeutic solutions for better disease management.
Materials and methods: We employed a comprehensive approach combining mathematical modeling and efficient parameter estimation to study the transient responses of regulatory proteins in both normal and virus-infected cells. Proportional-integral-derivative (PID) controllers were used to pinpoint specific protein targets for therapeutic intervention. Additionally, advanced deep learning models and molecular docking techniques were applied to analyze drug-target and drug-drug interactions, ensuring both efficacy and safety of the proposed treatments. This approach was applied to a case study focused on the cytokine storm in COVID-19, centering on Angiotensin-converting enzyme 2 (ACE2), which plays a key role in SARS-CoV-2 infection.
Results: Our findings suggest that activating ACE2 presents a promising therapeutic strategy, whereas inhibiting AT1R seems less effective. Deep learning models, combined with molecular docking, identified Lomefloxacin and Fostamatinib as stable drugs with no significant thermodynamic interactions, suggesting their safe concurrent use in managing COVID-19-induced cytokine storms.
Discussion: The results highlight the potential of ACE2 activation in mitigating lung injury and severe inflammation caused by SARS-CoV-2. This integrated approach accelerates the identification of safe and effective treatment options for emerging viral variants.
Conclusion: This framework provides an efficient method for identifying critical regulatory proteins and advancing drug repurposing, contributing to the rapid development of therapeutic strategies for COVID-19 and future global pandemics.
期刊介绍:
JAMIA is AMIA''s premier peer-reviewed journal for biomedical and health informatics. Covering the full spectrum of activities in the field, JAMIA includes informatics articles in the areas of clinical care, clinical research, translational science, implementation science, imaging, education, consumer health, public health, and policy. JAMIA''s articles describe innovative informatics research and systems that help to advance biomedical science and to promote health. Case reports, perspectives and reviews also help readers stay connected with the most important informatics developments in implementation, policy and education.