{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:59:15Z","timestamp":1791845955174,"version":"4.3.4"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>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 analyse 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jamia\/ocaf035","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T15:23:06Z","timestamp":1739287386000},"page":"193-209","source":"Crossref","is-referenced-by-count":6,"title":["Integrating state-space modeling, parameter estimation, deep learning, and docking techniques in drug repurposing: a case study on COVID-19 cytokine storm"],"prefix":"10.1093","volume":"33","author":[{"given":"Abhisek","family":"Bakshi","sequence":"first","affiliation":[{"name":"Department of Research and Development, Michelin India Private Limited , Pune, Maharashtra 411014,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaustav","family":"Gangopadhyay","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit","family":"Basak","sequence":"additional","affiliation":[{"name":"Department of Chemistry, GITAM (Deemed to be University) , Bengaluru, Karnataka 561203,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat K","family":"De","sequence":"additional","affiliation":[{"name":"Machine Intelligence Unit, Indian Statistical Institution , Kolkata, West Bengal 700108,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souvik","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Aliah University , Kolkata, West Bengal 700156,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6302-3512","authenticated-orcid":false,"given":"Abhijit","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105,","place":["United States"]},{"name":"Department of Computer Science and Engineering, SRM University AP , Amaravati, Andhra Pradesh 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