{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:21:24Z","timestamp":1792783284914,"version":"4.5.0"},"reference-count":109,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of KwaZulu-Natal","id":[{"id":"https:\/\/ror.org\/04qzfn040","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Biochem Biophys"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There has been a compelling need to identify new therapeutic targets and agents owing to the increasing complexity of disease mechanisms. Angiotensin-converting enzyme 2 (ACE2), the primary host receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, plays a crucial role in the pathophysiology of COVID-19, making ACE2 a potential biological target. Identification of small molecules that can interact with ACE2 may offer insights into a host-targeted approach relevant to viral entry and ACE2-associated cellular pathways. The study evaluated allosteric interactions of selected flavonoids with ACE2, the cytotoxicity and metabolic effects of the promising candidate in A549 cells through computational and in vitro methods. Molecular docking identified flavonoid binding to ACE2, followed by a 120 ns molecular dynamics (MD) simulation to characterize the stability and dynamic behaviour of ACE2-flavonoid complexes. MM\/GBSA binding free energy calculations and per residue energy decomposition were performed to identify key interactions stabilizing ligand binding. The in silico analyses showed ARG255, PRO328, GLU357, GLU384, GLU388, and ARG500 as the key allosteric residues contributing to ACE2-flavonoid complex stability. Rutin exhibited the most favourable binding affinity, followed by isoquercetin. Based on computational findings, rutin was selected for evaluation in A549 cells to assess cytotoxicity, metabolic and mitochondrial effects using MTT assay, ATP quantification, mitochondrial membrane potential (MMP), CYP3A4 activity and LDH release for membrane integrity. In vitro analyses showed that rutin is non-cytotoxic up to 500\u00b5M, enhances ATP production without adversely affecting MMP and membrane integrity. These findings indicate that rutin formed stable interactions with ACE2, with the potential to influence cellular energy metabolism without inducing cytotoxicity and therapeutic benefits in conditions linked to mitochondrial dysfunction and metabolic stress. While direct ACE2 enzymatic modulation was not confirmed experimentally, these findings provide a mechanistic basis for further studies on ACE2-flavonoid interactions and their potential biological implications in ACE2-associated diseases.<\/jats:p>","DOI":"10.1007\/s12013-026-02093-1","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:20:08Z","timestamp":1780921208000},"page":"3873-3898","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Allosteric Interactions of Flavonoids with ACE2 and Potential Implications for COVID-19: Computational Insights, Metabolic and Mitochondrial Effects of Rutin in A549 Cells"],"prefix":"10.1007","volume":"84","author":[{"given":"Fave Y.","family":"Tata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mthokozisi B.","family":"Nxumalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent A.","family":"Obakachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hezekiel M.","family":"Kumalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 B.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"2093_CR1","doi-asserted-by":"publisher","unstructured":"Omrani, M., Keshavarz, M., Nejad Ebrahimi, S., Mehrabi, M., McGaw, L. J., Ali Abdalla, M., & Mehrbod, P. (2021). Potential Natural Products Against Respiratory Viruses: A Perspective to Develop Anti-COVID-19 Medicines. Frontiers in Pharmacology, 11. https:\/\/doi.org\/10.3389\/fphar.2020.586993","DOI":"10.3389\/fphar.2020.586993"},{"key":"2093_CR2","doi-asserted-by":"publisher","unstructured":"Haddad, M., Gaudreault, R., Sasseville, G., Nguyen, P. T., Wiebe, H., Van De Ven, T., Bourgault, S., Mousseau, N., & Ramassamy, C. (2022). Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity. International Journal Of Molecular Sciences, 23(5). https:\/\/doi.org\/10.3390\/ijms23052643","DOI":"10.3390\/ijms23052643"},{"issue":"6","key":"2093_CR3","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.arcmed.2020.05.012","volume":"51","author":"S Satarker","year":"2020","unstructured":"Satarker, S., & Nampoothiri, M. (2020). Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2. Archives of Medical Research, 51(6), 482\u2013491. https:\/\/doi.org\/10.1016\/j.arcmed.2020.05.012","journal-title":"Archives of Medical Research"},{"issue":"1","key":"2093_CR4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s40199-023-00461-3","volume":"31","author":"L Toigo","year":"2023","unstructured":"Toigo, L., Dos Santos Teodoro, E. I., Guidi, A. C., Gancedo, N. C., Petruco, M. V., Melo, E. B., Tonin, F. S., Fernandez-Llimos, F., Chierrito, D., De Mello, J. C. P., De Medeiros, D. C., Ara\u00fajo, A. C. C., & Sanches (2023). Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies. DARU Journal of Pharmaceutical Sciences, 31(1), 51\u201368. https:\/\/doi.org\/10.1007\/s40199-023-00461-3","journal-title":"DARU Journal of Pharmaceutical Sciences"},{"key":"2093_CR5","doi-asserted-by":"publisher","unstructured":"Sender, R., Bar-On, Y. M., Gleizer, S., Bernshtein, B., Flamholz, A., Phillips, R., & Milo, R. (2021). The total number and mass of SARS-CoV-2 virions. Pnas 118(25), e2024815118 . https:\/\/doi.org\/10.1073\/pnas.2024815118","DOI":"10.1073\/pnas.2024815118"},{"issue":"4","key":"2093_CR6","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.cell.2020.09.037","volume":"183","author":"L Piccoli","year":"2020","unstructured":"Piccoli, L., Park, Y. J., Tortorici, M. A., Czudnochowski, N., Walls, A. C., Beltramello, M., Silacci-Fregni, C., Pinto, D., Rosen, L. E., & Bowen, J. E. (2020). Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Cell, 183(4), 1024\u20131042.","journal-title":"Cell"},{"key":"2093_CR7","doi-asserted-by":"publisher","first-page":"173620","DOI":"10.1016\/j.ejphar.2020.173620","volume":"890","author":"A Yarmohammadi","year":"2021","unstructured":"Yarmohammadi, A., Yarmohammadi, M., Fakhri, S., & Khan, H. (2021). Targeting pivotal inflammatory pathways in COVID-19: A mechanistic review. European Journal of Pharmacology, 890, 173620. https:\/\/doi.org\/10.1016\/j.ejphar.2020.173620","journal-title":"European Journal of Pharmacology"},{"issue":"21","key":"2093_CR8","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1042\/cs20200899","volume":"134","author":"L Lubbe","year":"2020","unstructured":"Lubbe, L., Gyles, D., Oosthuizen, K., & Edward (2020). ACE2 and ACE: structure-based insights into mechanism, regulation and receptor recognition by SARS-CoV. Clinical Science, 134(21), 2851\u20132871. https:\/\/doi.org\/10.1042\/cs20200899","journal-title":"Clinical Science"},{"issue":"1","key":"2093_CR9","doi-asserted-by":"publisher","first-page":"2000912","DOI":"10.1183\/13993003.00912-2020","volume":"56","author":"NE Ingraham","year":"2020","unstructured":"Ingraham, N. E., Barakat, A. G., Reilkoff, R., Bezdicek, T., Schacker, T., Chipman, J. G., Tignanelli, C. J., & Puskarich, M. A. (2020). Understanding the renin\u2013angiotensin\u2013aldosterone\u2013SARS-CoV axis: a comprehensive review. European Respiratory Journal, 56(1), 2000912. https:\/\/doi.org\/10.1183\/13993003.00912-2020","journal-title":"European Respiratory Journal"},{"issue":"7","key":"2093_CR10","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/jmv.25785","volume":"92","author":"H Cheng","year":"2020","unstructured":"Cheng, H., Wang, Y., & Wang, G. Q. (2020). Organ-protective effect of angiotensin\u2010converting enzyme 2 and its effect on the prognosis of COVID\u201019. Journal of medical virology, 92(7), 726\u2013730.","journal-title":"Journal of medical virology"},{"key":"2093_CR11","doi-asserted-by":"publisher","first-page":"170766","DOI":"10.1016\/j.peptides.2022.170766","volume":"151","author":"AJ Turner","year":"2022","unstructured":"Turner, A. J., & Nalivaeva, N. N. (2022). Angiotensin-converting enzyme 2 (ACE2): Two decades of revelations and re-evaluation. Peptides, 151, 170766. https:\/\/doi.org\/10.1016\/j.peptides.2022.170766","journal-title":"Peptides"},{"key":"2093_CR12","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3389\/fpubh.2020.00216","volume":"8","author":"R Keni","year":"2020","unstructured":"Keni, R., Alexander, A., Nayak, P. G., Mudgal, J., & Nandakumar, K. (2020). COVID-19: emergence, spread, possible treatments, and global burden. Frontiers in public health, 8, 216.","journal-title":"Frontiers in public health"},{"key":"2093_CR13","doi-asserted-by":"publisher","unstructured":"Stein, R. A. (2020). The 2019 coronavirus: Learning curves, lessons, and the weakest link. International Journal of Clinical Practice 74(4), e13488. https:\/\/doi.org\/10.1111\/ijcp.13488","DOI":"10.1111\/ijcp.13488"},{"issue":"22","key":"2093_CR14","doi-asserted-by":"publisher","first-page":"22425","DOI":"10.18632\/aging.202225","volume":"12","author":"B Wang","year":"2020","unstructured":"Wang, B., Kovalchuk, A., Li, D., Rodriguez-Juarez, R., Ilnytskyy, Y., Kovalchuk, I., & Kovalchuk, O. (2020). In search of preventive strategies: novel high-CBD Cannabis sativa extracts modulate ACE2 expression in COVID-19 gateway tissues. Aging (Albany NY), 12(22), 22425\u201322444. https:\/\/doi.org\/10.18632\/aging.202225","journal-title":"Aging (Albany NY)"},{"key":"2093_CR15","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.yjmcc.2020.04.031","volume":"144","author":"S Gro\u00df","year":"2020","unstructured":"Gro\u00df, S., Jahn, C., Cushman, S., B\u00e4r, C., & Thum, T. (2020). SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications. Journal of Molecular and Cellular Cardiology, 144, 47\u201353. https:\/\/doi.org\/10.1016\/j.yjmcc.2020.04.031","journal-title":"Journal of Molecular and Cellular Cardiology"},{"key":"2093_CR16","doi-asserted-by":"publisher","unstructured":"Li, S., Jiang, L., Li, X., Lin, F., Wang, Y., Li, B., Jiang, T., An, W., Liu, S., Liu, H., Xu, P., Zhao, L., Zhang, L., Mu, J., Wang, H., Kang, J., Li, Y., Huang, L., Zhu, C., Zhao, S., Lu, J., Ji, J., & Zhao, J. (2020). Clinical and pathological investigation of patients with severe COVID-19. JCI Insight, 5(12). https:\/\/doi.org\/10.1172\/jci.insight.138070","DOI":"10.1172\/jci.insight.138070"},{"issue":"1","key":"2093_CR17","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s13063-022-06075-5","volume":"23","author":"G C\u00e1rdenas","year":"2022","unstructured":"C\u00e1rdenas, G., Ch\u00e1vez-Canales, M., Espinosa, A. M., Jord\u00e1n-R\u00edos, A., Malagon, D. A., Murillo, M. F. M., Araujo, L. V. T., Campos, R. L. B., Wong-Chew, R. M., Gonz\u00e1lez, L. E. R., et al. (2022). Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients. Trials, 23(1), 148. https:\/\/doi.org\/10.1186\/s13063-022-06075-5","journal-title":"Trials"},{"issue":"6","key":"2093_CR18","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/s2213-2600(22)00002-9","volume":"10","author":"JR Baker","year":"2022","unstructured":"Baker, J. R., Mahdi, M., NicolauJr., D. V., Ramakrishnan, S., Barnes, P. J., Simpson, J. L., Cass, S. P., Russell, R. E. K., Donnelly, L. E., & Bafadhel, M. (2022). Early Th2 inflammation in the upper respiratory mucosa as a predictor of severe COVID-19 and modulation by early treatment with inhaled corticosteroids: a mechanistic analysis. Lancet Respir Med, 10(6), 545\u2013556. https:\/\/doi.org\/10.1016\/s2213-2600(22)00002-9","journal-title":"Lancet Respir Med"},{"issue":"8","key":"2093_CR19","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1164\/rccm.200912-1840OC","volume":"182","author":"V Shenoy","year":"2010","unstructured":"Shenoy, V., Ferreira, A. J., Qi, Y., Fraga-Silva, R. A., D\u00edez-Freire, C., Dooies, A., Jun, J. Y., Sriramula, S., Mariappan, N., Pourang, D., Venugopal, C. S., Francis, J., Reudelhuber, T., Santos, R. A., Patel, J. M., Raizada, M. K., & Katovich, M. J. (2010). The angiotensin-converting enzyme 2\/angiogenesis-(1\u20137)\/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. American Journal Of Respiratory And Critical Care Medicine, 182(8), 1065\u20131072. https:\/\/doi.org\/10.1164\/rccm.200912-1840OC","journal-title":"American Journal Of Respiratory And Critical Care Medicine"},{"issue":"13","key":"2093_CR20","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.3390\/cells11132102","volume":"11","author":"AK Ciechanowicz","year":"2022","unstructured":"Ciechanowicz, A. K., Lay, W. X., Prado Paulino, J., Suchocki, E., Leszczak, S., Leszczak, C., & Kucia, M. (2022). Angiotensin 1\u20137 Stimulates Proliferation of Lung Bronchoalveolar Progenitors\u2014Implications for SARS-CoV-2 Infection. Cells, 11(13), 2102.","journal-title":"Cells"},{"issue":"7","key":"2093_CR21","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1681\/asn.2021091209","volume":"33","author":"L Hassler","year":"2022","unstructured":"Hassler, L., Wysocki, J., Gelarden, I., Sharma, I., Tomatsidou, A., Ye, M., Gula, H., Nicoleascu, V., Randall, G., Pshenychnyi, S., Khurram, N., Kanwar, Y., Missiakas, D., Henkin, J., Yeldandi, A., & Batlle, D. (2022). A Novel Soluble ACE2 Protein Provides Lung and Kidney Protection in Mice Susceptible to Lethal SARS-CoV-2 Infection. Journal Of The American Society Of Nephrology, 33(7), 1293\u20131307. https:\/\/doi.org\/10.1681\/asn.2021091209","journal-title":"Journal Of The American Society Of Nephrology"},{"issue":"4","key":"2093_CR22","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1164\/rccm.201712-2570OC","volume":"198","author":"J Zhang","year":"2018","unstructured":"Zhang, J., Dong, J., Martin, M., He, M., Gongol, B., Marin, T. L., Chen, L., Shi, X., Yin, Y., Shang, F., Wu, Y., Huang, H. Y., Zhang, J., Zhang, Y., Kang, J., Moya, E. A., Huang, H. D., Powell, F. L., Chen, Z., Thistlethwaite, P. A., Yuan, Z. Y., & John, Y. J. (2018). AMP-activated protein kinase phosphorylation of angiotensin-converting enzyme 2 in endothelium mitigates pulmonary hypertension. American Journal Of Respiratory And Critical Care Medicine, 198(4), 509\u2013520. https:\/\/doi.org\/10.1164\/rccm.201712-2570OC","journal-title":"American Journal Of Respiratory And Critical Care Medicine"},{"issue":"4","key":"2093_CR23","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.dsx.2020.05.013","volume":"14","author":"M Marhl","year":"2020","unstructured":"Marhl, M., Grubelnik, V., Magdi\u010d, M., & Markovi\u010d, R. (2020). Diabetes and metabolic syndrome as risk factors for COVID-19, Diabetes and Metabolic Syndrome. Clinical Research and Reviews, 14(4), 671\u2013677. https:\/\/doi.org\/10.1016\/j.dsx.2020.05.013","journal-title":"Clinical Research and Reviews"},{"key":"2093_CR24","doi-asserted-by":"publisher","first-page":"8896536","DOI":"10.1155\/2020\/8896536","volume":"2020","author":"E Nigro","year":"2020","unstructured":"Nigro, E., Perrotta, F., Polito, R., D\u2019Agnano, V., Scial\u00f2, F., Bianco, A., & Daniele, A. (2020). Metabolic Perturbations and Severe COVID-19 Disease: Implication of Molecular Pathways. Int J Endocrinol, 2020, 8896536. https:\/\/doi.org\/10.1155\/2020\/8896536","journal-title":"Int J Endocrinol"},{"issue":"7","key":"2093_CR25","doi-asserted-by":"publisher","first-page":"6049","DOI":"10.18632\/aging.103000","volume":"12","author":"B Wang","year":"2020","unstructured":"Wang, B., Li, R., Lu, Z., & Huang, Y. (2020). Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging (albany NY), 12(7), 6049.","journal-title":"Aging (albany NY)"},{"key":"2093_CR26","doi-asserted-by":"publisher","first-page":"113089","DOI":"10.1016\/j.biopha.2022.113089","volume":"151","author":"P Sharma","year":"2022","unstructured":"Sharma, P., Behl, T., Sharma, N., Singh, S., Grewal, A. S., Albarrati, A., Albratty, M., Meraya, A. M., & Bungau, S. (2022). COVID-19 and diabetes: Association intensify risk factors for morbidity and mortality. Biomedicine & Pharmacotherapy, 151, 113089. https:\/\/doi.org\/10.1016\/j.biopha.2022.113089","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"2093_CR27","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1007\/s11427-020-1643-8","volume":"63","author":"Y Liu","year":"2020","unstructured":"Liu, Y., Yang, Y., Zhang, C., Huang, F., Wang, F., Yuan, J., Wang, Z., Li, J., Li, J., & Feng, C. (2020). Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life Sciences, 63, 364\u2013374.","journal-title":"Science China Life Sciences"},{"issue":"7","key":"2093_CR28","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.4239\/wjd.v12.i7.1026","volume":"12","author":"R Viurcos-Sanabria","year":"2021","unstructured":"Viurcos-Sanabria, R., & Escobedo, G. (2021). Immunometabolic bases of type 2 diabetes in the severity of COVID-19. World J Diabetes, 12(7), 1026\u20131041. https:\/\/doi.org\/10.4239\/wjd.v12.i7.1026","journal-title":"World J Diabetes"},{"issue":"1","key":"2093_CR29","first-page":"5794350","volume":"2022","author":"YO Ali Abdalla","year":"2022","unstructured":"Ali Abdalla, Y. O., Subramaniam, B., Nyamathulla, S., Shamsuddin, N., Arshad, N. M., Mun, K. S., Awang, K., & Nagoor, N. H. (2022). Natural products for cancer therapy: a review of their mechanism of actions and toxicity in the past decade. Journal of Tropical Medicine, 2022(1), 5794350.","journal-title":"Journal of Tropical Medicine"},{"issue":"1","key":"2093_CR30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ajps.2017.08.004","volume":"13","author":"T Wang","year":"2018","unstructured":"Wang, T., Li, Q., & Bi, K. (2018). Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian Journal of Pharmaceutical Sciences, 13(1), 12\u201323. https:\/\/doi.org\/10.1016\/j.ajps.2017.08.004","journal-title":"Asian Journal of Pharmaceutical Sciences"},{"issue":"4","key":"2093_CR31","doi-asserted-by":"publisher","first-page":"2884","DOI":"10.3390\/cimb46040181","volume":"46","author":"B Hao","year":"2024","unstructured":"Hao, B., Yang, Z., Liu, H., Liu, Y., & Wang, S. (2024). Advances in flavonoid research: Sources, biological activities, and developmental prospectives. Current Issues in Molecular Biology, 46(4), 2884\u20132925.","journal-title":"Current Issues in Molecular Biology"},{"key":"2093_CR32","doi-asserted-by":"publisher","unstructured":"Kumar, S., Paul, P., Yadav, P., Kaul, R., Maitra, S. S., Jha, S. K., & Chaari, A. (2022). A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle. Computers in Biology and Medicine, 142. https:\/\/doi.org\/10.1016\/j.compbiomed.2022.105231","DOI":"10.1016\/j.compbiomed.2022.105231"},{"key":"2093_CR33","doi-asserted-by":"publisher","unstructured":"Al-Shuhaib, M. B. S., Hashim, H. O., & Al-Shuhaib, J. M. B. (2022). Epicatechin is a promising novel inhibitor of SARS-CoV-2 entry by disrupting interactions between angiotensin-converting enzyme type 2 and the viral receptor binding domain: A computational\/simulation study. Computers in Biology and Medicine, 141. https:\/\/doi.org\/10.1016\/j.compbiomed.2021.105155","DOI":"10.1016\/j.compbiomed.2021.105155"},{"key":"2093_CR34","doi-asserted-by":"publisher","unstructured":"Dejani, N. N., Elshabrawy, H. A., & Bezerra Filho, C. D. S. M. (2021). de Sousa, Anticoronavirus and immunomodulatory phenolic compounds: Opportunities and pharmacotherapeutic perspectives. Biomolecules, 11(8). https:\/\/doi.org\/10.3390\/biom11081254","DOI":"10.3390\/biom11081254"},{"issue":"11","key":"2093_CR35","doi-asserted-by":"publisher","first-page":"5175","DOI":"10.1080\/07391102.2020.1868340","volume":"40","author":"C Sakshi","year":"2022","unstructured":"Sakshi, C., Harikrishnan, A., Jayaraman, S., Choudhury, A. R., & Veena, V. (2022). Predictive medicinal metabolites from Momordica dioica against comorbidity related proteins of SARS-CoV-2 infections. Journal of Biomolecular Structure and Dynamics, 40(11), 5175\u20135188. https:\/\/doi.org\/10.1080\/07391102.2020.1868340","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"2093_CR36","doi-asserted-by":"publisher","unstructured":"Mouffouk, C., Mouffouk, S., Mouffouk, S., Hambaba, L., & Haba, H. (2021). Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2). European Journal of Pharmacology, 891. https:\/\/doi.org\/10.1016\/j.ejphar.2020.173759","DOI":"10.1016\/j.ejphar.2020.173759"},{"issue":"D1","key":"2093_CR37","doi-asserted-by":"publisher","first-page":"D488","DOI":"10.1093\/nar\/gkac1077","volume":"51","author":"SK Burley","year":"2023","unstructured":"Burley, S. K., Bhikadiya, C., Bi, C., Bittrich, S., Chao, H., Chen, L., Craig, P. A., Crichlow, G. V., Dalenberg, K., Duarte, J. M., & RCSB Protein Data Bank (RCSB. (2023). org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence\/machine learning. Nucleic Acids Research, 51(D1), D488\u2013D508.","journal-title":"Nucleic Acids Research"},{"issue":"11","key":"2093_CR38","doi-asserted-by":"publisher","first-page":"e4792","DOI":"10.1002\/pro.4792","volume":"32","author":"EC Meng","year":"2023","unstructured":"Meng, E. C., Goddard, T. D., Pettersen, E. F., Couch, G. S., Pearson, Z. J., Morris, J. H., & Ferrin, T. E. (2023). UCSF ChimeraX: Tools for structure building and analysis. Protein Science, 32(11), e4792.","journal-title":"Protein Science"},{"issue":"1","key":"2093_CR39","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","volume":"30","author":"EF Pettersen","year":"2021","unstructured":"Pettersen, E. F., Goddard, T. D., Huang, C. C., Meng, E. C., Couch, G. S., Croll, T. I., Morris, J. H., & Ferrin, T. E. (2021). UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein science, 30(1), 70\u201382.","journal-title":"Protein science"},{"issue":"2","key":"2093_CR40","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455\u2013461.","journal-title":"Journal of computational chemistry"},{"key":"2093_CR41","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1146\/annurev-biochem-030222-120000","volume":"93","author":"JM Paggi","year":"2024","unstructured":"Paggi, J. M., Pandit, A., & Dror, R. O. (2024). The art and science of molecular docking. Annual Review of Biochemistry, 93, 389\u2013410. https:\/\/doi.org\/10.1146\/annurev-biochem-030222-120000","journal-title":"Annual Review of Biochemistry"},{"issue":"1","key":"2093_CR42","doi-asserted-by":"publisher","first-page":"22","DOI":"10.24198\/ijcb.v2i1.46322","volume":"2","author":"U Baroroh","year":"2023","unstructured":"Baroroh, U., Biotek, M., Muscifa, Z. S., Destiarani, W., Rohmatullah, F. G., & Yusuf, M. (2023). Molecular interaction analysis and visualization of protein-ligand docking using Biovia Discovery Studio Visualizer. Indonesian Journal of Computational Biology (IJCB), 2(1), 22\u201330.","journal-title":"Indonesian Journal of Computational Biology (IJCB)"},{"key":"2093_CR43","doi-asserted-by":"publisher","unstructured":"Ugbaja, S. C., Mtambo, S. E., Mushebenge, A. G., Appiah-Kubi, P., Abubakar, B. H., Ntuli, M. L., & Kumalo, H. M. (2022). Structural Investigations and Binding Mechanisms of Oseltamivir Drug Resistance Conferred by the E119V Mutation in Influenza H7N9 Virus. Molecules, 27(14). https:\/\/doi.org\/10.3390\/molecules27144376","DOI":"10.3390\/molecules27144376"},{"key":"2093_CR44","doi-asserted-by":"publisher","first-page":"101920","DOI":"10.1016\/j.tube.2020.101920","volume":"121","author":"OI Akinpelu","year":"2020","unstructured":"Akinpelu, O. I., Lawal, M. M., Kumalo, H. M., & Mhlongo, N. N. (2020). Drug repurposing: Fusidic acid as a potential inhibitor of M. tuberculosis FtsZ polymerization \u2013 Insight from DFT calculations, molecular docking and molecular dynamics simulations. Tuberculosis, 121, 101920. https:\/\/doi.org\/10.1016\/j.tube.2020.101920","journal-title":"Tuberculosis"},{"issue":"9","key":"2093_CR45","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.1080\/07391102.2022.2062786","volume":"41","author":"A Sinyani","year":"2023","unstructured":"Sinyani, A., Idowu, K., Shunmugam, L., Kumalo, H. M., & Khan, R. (2023). A molecular dynamics perspective into estrogen receptor inhibition by selective flavonoids as alternative therapeutic options. Journal of Biomolecular Structure and Dynamics, 41(9), 4093\u20134105.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"6","key":"2093_CR46","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.neuron.2018.08.011","volume":"99","author":"SA Hollingsworth","year":"2018","unstructured":"Hollingsworth, S. A., & Dror, R. O. (2018). Molecular dynamics simulation for all. Neuron, 99(6), 1129\u20131143.","journal-title":"Neuron"},{"issue":"8","key":"2093_CR47","doi-asserted-by":"publisher","first-page":"e18103","DOI":"10.1002\/aic.18103","volume":"69","author":"Y Zhao","year":"2023","unstructured":"Zhao, Y., Gee, R., & Doherty, M. F. (2023). Morphology prediction for organic molecular crystals using various force fields in ADDICT. AIChE Journal, 69(8), e18103.","journal-title":"AIChE Journal"},{"issue":"73","key":"2093_CR48","doi-asserted-by":"publisher","first-page":"42210","DOI":"10.1039\/C8RA07346E","volume":"8","author":"L Shunmugam","year":"2018","unstructured":"Shunmugam, L., & Soliman, M. E. S. (2018). Targeting HCV polymerase: a structural and dynamic perspective into the mechanism of selective covalent inhibition. RSC advances, 8(73), 42210\u201342222.","journal-title":"RSC advances"},{"issue":"14","key":"2093_CR49","doi-asserted-by":"publisher","first-page":"4515","DOI":"10.3390\/molecules27144515","volume":"27","author":"SE Mtambo","year":"2022","unstructured":"Mtambo, S. E., & Kumalo, H. M. (2022). In Silico Drug Repurposing of FDA-Approved Drugs Highlighting Promacta as a Potential Inhibitor of H7N9 Influenza Virus. Molecules, 27(14), 4515.","journal-title":"Molecules"},{"issue":"8","key":"2093_CR50","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1021\/acs.jctc.5b00093","volume":"11","author":"BA Wells","year":"2015","unstructured":"Wells, B. A., & Chaffee, A. L. (2015). Ewald summation for molecular simulations. Journal of chemical theory and computation, 11(8), 3684\u20133695.","journal-title":"Journal of chemical theory and computation"},{"issue":"8","key":"2093_CR51","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1007\/s12033-023-00831-x","volume":"66","author":"AM da Fonseca","year":"2024","unstructured":"da Fonseca, A. M., Caluaco, B. J., Madureira, J. M. C., Cabongo, S. Q., Gaieta, E. M., Djata, F., Colares, R. P., Neto, M. M., Fernandes, C. F. C., & Marinho, G. S. (2024). Screening of potential inhibitors targeting the main protease structure of SARS-CoV-2 via molecular docking, and approach with molecular dynamics, RMSD, RMSF, H-bond, SASA and MMGBSA. Molecular Biotechnology, 66(8), 1919\u20131933.","journal-title":"Molecular Biotechnology"},{"key":"2093_CR52","doi-asserted-by":"publisher","first-page":"101920","DOI":"10.1016\/j.tube.2020.101920","volume":"121","author":"OI Akinpelu","year":"2020","unstructured":"Akinpelu, O. I., Lawal, M. M., Kumalo, H. M., & Mhlongo, N. N. (2020). Drug repurposing: Fusidic acid as a potential inhibitor of M. tuberculosis FtsZ polymerization\u2013Insight from DFT calculations, molecular docking and molecular dynamics simulations. Tuberculosis, 121, 101920.","journal-title":"Tuberculosis"},{"issue":"6","key":"2093_CR53","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1080\/07391102.2023.2294839","volume":"43","author":"S Zaib","year":"2025","unstructured":"Zaib, S., Rana, N., Ali, H. S., ur Rehman, M., Awwad, N. S., Ibrahium, H. A., & Khan, I. (2025). Identification of potential inhibitors targeting yellow fever virus helicase through ligand and structure-based computational studies. Journal of Biomolecular Structure and Dynamics, 43(6), 3031\u20133048.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"4","key":"2093_CR54","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1080\/07391102.2016.1165736","volume":"35","author":"N Chaudhary","year":"2017","unstructured":"Chaudhary, N., & Aparoy, P. (2017). Deciphering the mechanism behind the varied binding activities of COXIBs through Molecular Dynamic Simulations, MM-PBSA binding energy calculations and per-residue energy decomposition studies. Journal of Biomolecular Structure and Dynamics, 35(4), 868\u2013882.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"2093_CR55","doi-asserted-by":"publisher","unstructured":"Chaudhary, N., & Aparoy, P. (2020). Application of per-residue energy decomposition to identify the set of amino acids critical for in silico prediction of COX-2 inhibitory activity. Heliyon 6(10), e04944. https:\/\/doi.org\/10.1016\/j.heliyon.2020.e04944","DOI":"10.1016\/j.heliyon.2020.e04944"},{"issue":"16","key":"2093_CR56","doi-asserted-by":"publisher","first-page":"3437","DOI":"10.3390\/nu14163437","volume":"14","author":"MA Rhman","year":"2022","unstructured":"Rhman, M. A., Devnarain, N., Khan, R., & Owira, P. M. O. (2022). Synergism potentiates oxidative antiproliferative effects of naringenin and quercetin in MCF-7 breast cancer cells. Nutrients, 14(16), 3437.","journal-title":"Nutrients"},{"issue":"6","key":"2093_CR57","doi-asserted-by":"publisher","first-page":"483","DOI":"10.2174\/1389200043335397","volume":"5","author":"G Luo","year":"2004","unstructured":"Luo, G., Guenthner, T., Gan, L. S., & Humphreys, W. G. (2004). CYP3A4 induction by xenobiotics: biochemistry, experimental methods and impact on drug discovery and development. Current drug metabolism, 5(6), 483\u2013505.","journal-title":"Current drug metabolism"},{"issue":"11","key":"2093_CR58","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.3390\/biomedicines10112686","volume":"10","author":"LS Klyushova","year":"2022","unstructured":"Klyushova, L. S., Perepechaeva, M. L., & Grishanova, A. Y. (2022). The role of CYP3A in health and disease. Biomedicines, 10(11), 2686.","journal-title":"Biomedicines"},{"issue":"4","key":"2093_CR59","first-page":"703","volume":"22","author":"Z Nozhat","year":"2022","unstructured":"Nozhat, Z., Khalaji, M. S., Hedayati, M., & Kia, S. K. (2022). Different methods for cell viability and proliferation assay: essential tools in pharmaceutical studies, Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti. -Cancer Agents), 22(4), 703\u2013712.","journal-title":"-Cancer Agents)"},{"issue":"6","key":"2093_CR60","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3390\/cells13060493","volume":"13","author":"PT Morse","year":"2024","unstructured":"Morse, P. T., Arroum, T., Wan, J., Pham, L., Vaishnav, A., Bell, J., Pavelich, L., Malek, M. H., Sanderson, T. H., & Edwards, B. F. P. (2024). Phosphorylations and acetylations of cytochrome c control mitochondrial respiration, mitochondrial membrane potential, energy, ROS, and apoptosis. Cells, 13(6), 493.","journal-title":"Cells"},{"issue":"3","key":"2093_CR61","doi-asserted-by":"publisher","first-page":"480","DOI":"10.2174\/1570180819666220922103109","volume":"21","author":"MT Muhammed","year":"2024","unstructured":"Muhammed, M. T., & Aki-Yalcin, E. (2024). Molecular docking: principles, advances, and its applications in drug discovery. Letters in Drug Design & Discovery, 21(3), 480\u2013495.","journal-title":"Letters in Drug Design & Discovery"},{"issue":"40","key":"2093_CR62","doi-asserted-by":"publisher","first-page":"12899","DOI":"10.1039\/c0cp00151a","volume":"12","author":"SY Huang","year":"2010","unstructured":"Huang, S. Y., Grinter, S. Z., & Zou, X. (2010). Scoring functions and their evaluation methods for protein\u2013ligand docking: recent advances and future directions. Physical Chemistry Chemical Physics, 12(40), 12899\u201312908.","journal-title":"Physical Chemistry Chemical Physics"},{"issue":"2","key":"2093_CR63","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1080\/07391102.2020.1815584","volume":"40","author":"C Shivanika","year":"2022","unstructured":"Shivanika, C., Deepak Kumar, S., Ragunathan, V., Tiwari, P., Sumitha, A., Brindha, P., & Devi (2022). Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. Journal of Biomolecular Structure and Dynamics, 40(2), 585\u2013611. https:\/\/doi.org\/10.1080\/07391102.2020.1815584","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"20","key":"2093_CR64","doi-asserted-by":"publisher","first-page":"10250","DOI":"10.1080\/07391102.2021.1942213","volume":"40","author":"Z Aliakbar Tehrani","year":"2022","unstructured":"Aliakbar Tehrani, Z., Rul\u00ed\u0161ek, L., & \u010cern\u00fd, J. (2022). Molecular dynamics simulations provide structural insight into binding of cyclic dinucleotides to human STING protein. Journal of Biomolecular Structure and Dynamics, 40(20), 10250\u201310264.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"1","key":"2093_CR65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s44386-024-00001-2","volume":"1","author":"H Wei","year":"2024","unstructured":"Wei, H., & McCammon, J. A. (2024). Structure and dynamics in drug discovery. npj Drug Discovery, 1(1), 1\u20138.","journal-title":"npj Drug Discovery"},{"key":"2093_CR66","doi-asserted-by":"publisher","first-page":"135604","DOI":"10.1016\/j.molstruc.2023.135604","volume":"1286","author":"JCM Lobato","year":"2023","unstructured":"Lobato, J. C. M., da Silva Arouche, T., Del Nero, J., dos Santos Borges, R., & Neto, A. M. J. C. (2023). Interactions between carbon nanotubes and external structures of SARS-CoV-2 using molecular docking and molecular dynamics. Journal of Molecular Structure, 1286, 135604.","journal-title":"Journal of Molecular Structure"},{"issue":"1","key":"2093_CR67","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/s42003-022-03416-7","volume":"5","author":"I Yasuda","year":"2022","unstructured":"Yasuda, I., Endo, K., Yamamoto, E., Hirano, Y., & Yasuoka, K. (2022). Differences in ligand-induced protein dynamics extracted from an unsupervised deep learning approach correlate with protein\u2013ligand binding affinities. Communications biology, 5(1), 481.","journal-title":"Communications biology"},{"key":"2093_CR68","doi-asserted-by":"publisher","unstructured":"Madasu, P. K., & Chandran, T. (2024). Structural insights into the toxicity of type II ribosome inactivating proteins (RIPs): a molecular dynamics study. Journal of Biomolecular Structure and Dynamics, 1\u201312. https:\/\/doi.org\/10.1080\/07391102.2024.2419855","DOI":"10.1080\/07391102.2024.2419855"},{"issue":"S1","key":"2093_CR69","doi-asserted-by":"publisher","first-page":"S190","DOI":"10.1002\/mrc.953","volume":"39","author":"PA Frey","year":"2001","unstructured":"Frey, P. A. (2001). Strong hydrogen bonding in molecules and enzymatic complexes. Magnetic Resonance in Chemistry, 39(S1), S190\u2013S198.","journal-title":"Magnetic Resonance in Chemistry"},{"issue":"2","key":"2093_CR70","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3390\/biom13020235","volume":"13","author":"F Sebastiani","year":"2023","unstructured":"Sebastiani, F., Baroni, C., Patil, G., Dali, A., Becucci, M., Hofbauer, S., & Smulevich, G. (2023). The Role of the Hydrogen Bond Network in Maintaining Heme Pocket Stability and Protein Function Specificity of C. diphtheriae Coproheme Decarboxylase. Biomolecules, 13(2), 235.","journal-title":"Biomolecules"},{"issue":"3","key":"2093_CR71","doi-asserted-by":"publisher","first-page":"bbaa107","DOI":"10.1093\/bib\/bbaa107","volume":"22","author":"DD Wang","year":"2021","unstructured":"Wang, D. D., Zhu, M., & Yan, H. (2021). Computationally predicting binding affinity in protein\u2013ligand complexes: free energy-based simulations and machine learning-based scoring functions. Briefings in bioinformatics, 22(3), bbaa107.","journal-title":"Briefings in bioinformatics"},{"issue":"6","key":"2093_CR72","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.3390\/molecules28062583","volume":"28","author":"L Wang","year":"2023","unstructured":"Wang, L., Wang, Y., Yu, Y., Liu, D., Zhao, J., & Zhang, L. (2023). Deciphering Selectivity Mechanism of BRD9 and TAF1 (2) toward Inhibitors Based on Multiple Short Molecular Dynamics Simulations and MM-GBSA Calculations. Molecules, 28(6), 2583.","journal-title":"Molecules"},{"issue":"1","key":"2093_CR73","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1146\/annurev-physchem-040412-110047","volume":"64","author":"R Baron","year":"2013","unstructured":"Baron, R., & McCammon, J. A. (2013). Molecular recognition and ligand association. Annual review of physical chemistry, 64(1), 151\u2013175.","journal-title":"Annual review of physical chemistry"},{"key":"2093_CR74","doi-asserted-by":"crossref","unstructured":"Vel\u00e1squez, P. A., Hernandez, J. C., Galeano, E., Hincapi\u00e9-Garc\u00eda, J., & Rugeles, M. T. (2024). W. Zapata-Builes, Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review, Clinical Pharmacology: Advances and Applications 1\u201325.","DOI":"10.2147\/CPAA.S429064"},{"issue":"20","key":"2093_CR75","doi-asserted-by":"publisher","first-page":"11069","DOI":"10.3390\/ijms222011069","volume":"22","author":"R Kaul","year":"2021","unstructured":"Kaul, R., Paul, P., Kumar, S., B\u00fcsselberg, D., Dwivedi, V. D., & Chaari, A. (2021). Promising antiviral activities of natural flavonoids against SARS-CoV-2 targets: systematic review. International journal of molecular sciences, 22(20), 11069.","journal-title":"International journal of molecular sciences"},{"key":"2093_CR76","doi-asserted-by":"publisher","unstructured":"Agrawal, P. K., Agrawal, C., & Blunden, G. (2021). Rutin: A Potential Antiviral for Repurposing as a SARS-CoV-2 Main Protease (M\u2009<\u2009sup>pro) Inhibitor. Natural Product Communications, 16(4). https:\/\/doi.org\/10.1177\/1934578X21991723","DOI":"10.1177\/1934578X21991723"},{"key":"2093_CR77","doi-asserted-by":"publisher","unstructured":"Mohanasundaram, S., Karthikeyan, P., Sampath, V., Anbazhagan, M., Prabhu, S. V., Khaled, J. M., Thiruvengadam, M., & Docking, M. (2024). Dynamics Simulations, ADMET, and DFT Calculations: Combined In Silico Approach to Screen Natural Inhibitors of 3CL and PL Proteases of SARS-CoV-2, Cellular Microbiology (2024) 1\u201319. https:\/\/doi.org\/10.1155\/2024\/6647757","DOI":"10.1155\/2024\/6647757"},{"issue":"10","key":"2093_CR78","doi-asserted-by":"publisher","first-page":"e0240653","DOI":"10.1371\/journal.pone.0240653","volume":"15","author":"SA Cherrak","year":"2020","unstructured":"Cherrak, S. A., Merzouk, H., & Mokhtari-Soulimane, N. (2020). Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies. Plos One, 15(10), e0240653.","journal-title":"Plos One"},{"key":"2093_CR79","doi-asserted-by":"publisher","first-page":"556481","DOI":"10.3389\/fmolb.2020.556481","volume":"7","author":"Z Xu","year":"2020","unstructured":"Xu, Z., Yang, L., Zhang, X., Zhang, Q., Yang, Z., Liu, Y., Wei, S., & Liu, W. (2020). Discovery of potential flavonoid inhibitors against COVID-19 3CL proteinase based on virtual screening strategy. Frontiers in molecular biosciences, 7, 556481.","journal-title":"Frontiers in molecular biosciences"},{"key":"2093_CR80","doi-asserted-by":"crossref","unstructured":"Fu, Y., Zhao, J., & Chen, Z. (2018). Insights into the molecular mechanisms of protein-ligand interactions by molecular docking and molecular dynamics simulation: A case of oligopeptide binding protein, Computational and mathematical methods in medicine (2018).","DOI":"10.1155\/2018\/3502514"},{"issue":"1","key":"2093_CR81","doi-asserted-by":"publisher","first-page":"22195","DOI":"10.1038\/s41598-021-01690-9","volume":"11","author":"H Caohuy","year":"2021","unstructured":"Caohuy, H., Eidelman, O., Chen, T., Liu, S., Yang, Q., Bera, A., Walton, N. I., Wang, T. T., & Pollard, H. B. (2021). Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells. Scientific Reports, 11(1), 22195.","journal-title":"Scientific Reports"},{"issue":"3","key":"2093_CR82","doi-asserted-by":"publisher","first-page":"e06515","DOI":"10.1016\/j.heliyon.2021.e06515","volume":"7","author":"D Bhowmik","year":"2021","unstructured":"Bhowmik, D., Nandi, R., Prakash, A., & Kumar, D. (2021). Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis. Heliyon, 7(3), e06515. https:\/\/doi.org\/10.1016\/j.heliyon.2021.e06515","journal-title":"Heliyon"},{"issue":"11","key":"2093_CR83","doi-asserted-by":"publisher","first-page":"5331","DOI":"10.1128\/jvi.02274-10","volume":"85","author":"K Wu","year":"2011","unstructured":"Wu, K., Chen, L., Peng, G., Zhou, W., Pennell, C. A., Mansky, L. M., Geraghty, R. J., & Li, F. (2011). A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses. Journal of Virology, 85(11), 5331\u20135337. https:\/\/doi.org\/10.1128\/jvi.02274-10","journal-title":"Journal of Virology"},{"issue":"6","key":"2093_CR84","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1080\/07391102.2022.2032354","volume":"41","author":"GKRS Naresh","year":"2023","unstructured":"Naresh, G. K. R. S., & Guruprasad, L. (2023). Mutations in the receptor-binding domain of human SARS CoV-2 spike protein increases its affinity to bind human ACE-2 receptor. Journal of Biomolecular Structure and Dynamics, 41(6), 2368\u20132381. https:\/\/doi.org\/10.1080\/07391102.2022.2032354","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"3","key":"2093_CR85","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1021\/acs.jmedchem.1c01978","volume":"65","author":"Z Wang","year":"2022","unstructured":"Wang, Z., Huang, W., Zhou, K., Ren, X., & Ding, K. (2022). Targeting the non-catalytic functions: a new paradigm for kinase drug discovery? Journal of Medicinal Chemistry, 65(3), 1735\u20131748.","journal-title":"Journal of Medicinal Chemistry"},{"issue":"8","key":"2093_CR86","doi-asserted-by":"publisher","first-page":"4281","DOI":"10.3390\/ijms25084281","volume":"25","author":"N Raisinghani","year":"2024","unstructured":"Raisinghani, N., Alshahrani, M., Gupta, G., & Verkhivker, G. (2024). Ensemble-Based Mutational Profiling and Network Analysis of the SARS-CoV-2 Spike Omicron XBB Lineages for Interactions with the ACE2 Receptor and Antibodies: Cooperation of Binding Hotspots in Mediating Epistatic Couplings Underlies Binding Mechanism and Immune Escape. International Journal of Molecular Sciences, 25(8), 4281.","journal-title":"International Journal of Molecular Sciences"},{"issue":"6","key":"2093_CR87","doi-asserted-by":"publisher","first-page":"784","DOI":"10.2174\/1573409919666230726142418","volume":"20","author":"T Li","year":"2024","unstructured":"Li, T., Yan, Z., Zhou, W., Liu, Q., Liu, J., & Hua, H. (2024). Discovery of a Potential Allosteric Site in the SARS-CoV-2 Spike Protein and Targeting Allosteric Inhibitor to Stabilize the RBD Down State using a Computational Approach. Current Computer-Aided Drug Design, 20(6), 784\u2013797.","journal-title":"Current Computer-Aided Drug Design"},{"key":"2093_CR88","doi-asserted-by":"publisher","unstructured":"Alshahrani, M., Gupta, G., Xiao, S., Tao, P., & Verkhivker, G. (2023). Comparative Analysis of Conformational Dynamics and Systematic Characterization of Cryptic Pockets in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 Spike Complexes with the ACE2 Host Receptor: Confluence of Binding and Structural Plasticity in Mediating Networks of Conserved Allosteric Sites. Viruses, 15(10). https:\/\/doi.org\/10.3390\/v15102073","DOI":"10.3390\/v15102073"},{"key":"2093_CR89","doi-asserted-by":"publisher","first-page":"149825","DOI":"10.1016\/j.bbrc.2024.149825","volume":"709","author":"O Kalashnyk","year":"2024","unstructured":"Kalashnyk, O., Lykhmus, O., Sullivan, R., Komisarenko, S., & Skok, M. (2024). Agonists or positive allosteric modulators of \u03b17 nicotinic acetylcholine receptor prevent interaction of SARS-Cov-2 receptor-binding domain with astrocytoma cells. Biochemical and Biophysical Research Communications, 709, 149825.","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"24","key":"2093_CR90","doi-asserted-by":"publisher","first-page":"13497","DOI":"10.1080\/07391102.2021.1989040","volume":"40","author":"M Kumari","year":"2022","unstructured":"Kumari, M., Singh, R., & Subbarao, N. (2022). Exploring the interaction mechanism between potential inhibitor and multi-target Mur enzymes of mycobacterium tuberculosis using molecular docking, molecular dynamics simulation, principal component analysis, free energy landscape, dynamic cross-correlation matrices, vector movements, and binding free energy calculation. Journal of Biomolecular Structure and Dynamics, 40(24), 13497\u201313526.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"1","key":"2093_CR91","doi-asserted-by":"publisher","first-page":"014111","DOI":"10.1063\/1.4885338","volume":"141","author":"F Sittel","year":"2014","unstructured":"Sittel, F., Jain, A., & Stock, G. (2014). Principal component analysis of molecular dynamics: On the use of Cartesian vs. internal coordinates. The Journal of Chemical Physics, 141(1), 014111. https:\/\/doi.org\/10.1063\/1.4885338","journal-title":"The Journal of Chemical Physics"},{"key":"2093_CR92","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-19485-6_18","author":"S Mani","year":"2023","unstructured":"Mani, S., & Swargiary, G. (2023). In Vitro Cytotoxicity Analysis: MTT\/XTT, Trypan Blue Exclusion. Techniques in Life Science and Biomedicine for the Non-Expert. https:\/\/doi.org\/10.1007\/978-3-031-19485-6_18","journal-title":"Techniques in Life Science and Biomedicine for the Non-Expert"},{"key":"2093_CR93","unstructured":"Riss, T., Niles, A., Moravec, R., & Karassina, N. (2019). J. Vidugiriene, Cytotoxicity assays: in vitro methods to measure dead cells."},{"key":"2093_CR94","doi-asserted-by":"crossref","unstructured":"De Jong, W. H., Carraway, J. W., & Geertsma, R. E. In vivo and in vitro testing for the biological safety evaluation of biomaterials and medical devices, Biocompatibility and performance of medical devices, Elsevier2020, pp. 123\u2013166. (Reprinted from.","DOI":"10.1016\/B978-0-08-102643-4.00007-0"},{"key":"2093_CR95","doi-asserted-by":"publisher","unstructured":"Szymanski, L., Golaszewska, K., Wiatrowska, A., Dropik, M., Szymanski, P., Gromadka, B., Krakowiak, P., Wierzchowska, J., & Matak, D. (2022). ISO 10993 biological evaluation of novel hemostatic powder \u2013 4SEAL\u00ae. Biomaterials Research, 26(1). https:\/\/doi.org\/10.1186\/s40824-022-00258-6","DOI":"10.1186\/s40824-022-00258-6"},{"key":"2093_CR96","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/8867669","volume":"2020","author":"TT Hoai","year":"2020","unstructured":"Hoai, T. T., Yen, P. T., Dao, T. T. B., Long, L. H., Anh, D. X., Minh, L. H., Anh, B. Q., & Thuong, N. T. (2020). Evaluation of the Cytotoxic Effect of Rutin Prenanoemulsion in Lung and Colon Cancer Cell Lines. Journal of Nanomaterials, 2020, 1\u201311. https:\/\/doi.org\/10.1155\/2020\/8867669","journal-title":"Journal of Nanomaterials"},{"key":"2093_CR97","unstructured":"Riss,T. L., Moravec, R. A., Niles, A. L., Duellman, S., Benink, H. A., Worzella, T. J., & Minor, L. (2004). Cell Viability Assays. Assay Guidance Manual: Eli Lilly & Company and the National Center for Advancing Translational Sciences: Bethesda,MD, USA. 1\u201331. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23805433"},{"key":"2093_CR98","unstructured":"Farhana, A., & Lappin, S. L. Biochemistry, lactate dehydrogenase, Stat Pearls Publishing 2023. (Reprinted from)."},{"issue":"23","key":"2093_CR99","doi-asserted-by":"publisher","first-page":"7871","DOI":"10.3390\/molecules28237871","volume":"28","author":"AS Aloufi","year":"2023","unstructured":"Aloufi, A. S., Habotta, O. A., Abdelfattah, M. S., Habib, M. N., Omran, M. M., Ali, S. A., Abdel Moneim, A. E., Korany, S. M., & Alrajhi, A. M. (2023). Resistomycin Suppresses Prostate Cancer Cell Growth by Instigating Oxidative Stress, Mitochondrial Apoptosis, and Cell Cycle Arrest. Molecules, 28(23), 7871.","journal-title":"Molecules"},{"issue":"3","key":"2093_CR100","doi-asserted-by":"publisher","first-page":"e0150303","DOI":"10.1371\/journal.pone.0150303","volume":"11","author":"W Ye","year":"2016","unstructured":"Ye, W., Zheng, Y., Zhang, S., Yan, L., Cheng, H., & Wu, M. (2016). Oxamate Improves Glycemic Control and Insulin Sensitivity via Inhibition of Tissue Lactate Production in db\/db Mice. Plos One, 11(3), e0150303. https:\/\/doi.org\/10.1371\/journal.pone.0150303","journal-title":"Plos One"},{"issue":"2","key":"2093_CR101","doi-asserted-by":"publisher","first-page":"R227","DOI":"10.1152\/ajpregu.00226.2022","volume":"324","author":"HC Shen","year":"2023","unstructured":"Shen, H. C., Chen, Z. Q., Liu, X. C., Guan, J. F., Xie, D. Z., Li, Y. Y., & Xu, C. (2023). Sodium oxamate reduces lactate production to improve the glucose homeostasis of Micropterus salmoides fed high-carbohydrate diets. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 324(2), R227\u2013R241.","journal-title":"American Journal of Physiology-Regulatory Integrative and Comparative Physiology"},{"key":"2093_CR102","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.cofs.2016.02.002","volume":"8","author":"H Zhang","year":"2016","unstructured":"Zhang, H., & Tsao, R. (2016). Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Current Opinion in Food Science, 8, 33\u201342.","journal-title":"Current Opinion in Food Science"},{"issue":"6","key":"2093_CR103","doi-asserted-by":"publisher","first-page":"3264","DOI":"10.3390\/ijms25063264","volume":"25","author":"A Muscolo","year":"2024","unstructured":"Muscolo, A., Mariateresa, O., Giulio, T., & Mariateresa, R. (2024). Oxidative stress: the role of antioxidant phytochemicals in the prevention and treatment of diseases. International journal of molecular sciences, 25(6), 3264.","journal-title":"International journal of molecular sciences"},{"issue":"5","key":"2093_CR104","doi-asserted-by":"publisher","first-page":"103560","DOI":"10.1016\/j.drudis.2023.103560","volume":"28","author":"M Zhou","year":"2023","unstructured":"Zhou, M., Li, J., Xu, J., Zheng, L., & Xu, S. (2023). Exploring human CYP4 enzymes: Physiological roles, function in diseases and focus on inhibitors. Drug Discovery Today, 28(5), 103560.","journal-title":"Drug Discovery Today"},{"key":"2093_CR105","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.pbiomolbio.2024.09.003","volume":"193","author":"IM Mokhosoev","year":"2024","unstructured":"Mokhosoev, I. M., Astakhov, D. V., Terentiev, A. A., & Moldogazieva, N. T. (2024). Cytochrome P450 monooxygenase systems: Diversity and plasticity for adaptive stress response. Progress in Biophysics and Molecular Biology, 193, 19\u201334. https:\/\/doi.org\/10.1016\/j.pbiomolbio.2024.09.003","journal-title":"Progress in Biophysics and Molecular Biology"},{"issue":"1612","key":"2093_CR106","doi-asserted-by":"publisher","first-page":"20120431","DOI":"10.1098\/rstb.2012.0431","volume":"368","author":"DW Nebert","year":"2013","unstructured":"Nebert, D. W., Wikvall, K., & Miller, W. L. (2013). Human cytochromes P450 in health and disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 368(1612), 20120431.","journal-title":"Philosophical Transactions of the Royal Society B: Biological Sciences"},{"key":"2093_CR107","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.toxlet.2019.11.016","volume":"319","author":"J Bai","year":"2020","unstructured":"Bai, J., Li, L., Zhao, S., Fan, X., Zhang, J., Hu, M., Chen, Y., Sun, Y., Wang, B., & Jin, J. (2020). Heterotropic activation of flavonoids on cytochrome P450 3A4: A case example of alleviating dronedarone-induced cytotoxicity. Toxicology Letters, 319, 187\u2013196.","journal-title":"Toxicology Letters"},{"issue":"3","key":"2093_CR108","doi-asserted-by":"publisher","first-page":"644","DOI":"10.3390\/biomedicines12030644","volume":"12","author":"M Kond\u017ea","year":"2024","unstructured":"Kond\u017ea, M., Brizi\u0107, I., & Joki\u0107, S. (2024). Flavonoids as CYP3A4 Inhibitors In Vitro. Biomedicines, 12(3), 644.","journal-title":"Biomedicines"},{"issue":"2","key":"2093_CR109","first-page":"1","volume":"57","author":"BA Alyami","year":"2023","unstructured":"Alyami, B. A., Zaki, M., Youns, M., Amin, B., Abdou, R., Dawoud, M., & Attia, G. H. (2023). Rutin Inhibits Hepatic and Pancreatic Cancer Cell Proliferation by Inhibiting CYP3A4 and GST. Ind J Pharm Edu Res, 57(2), 1\u20138.","journal-title":"Ind J Pharm Edu Res"}],"container-title":["Cell Biochemistry and Biophysics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12013-026-02093-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12013-026-02093-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12013-026-02093-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:03:06Z","timestamp":1789635786000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12013-026-02093-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":109,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["2093"],"URL":"https:\/\/doi.org\/10.1007\/s12013-026-02093-1","relation":{},"ISSN":["1559-0283"],"issn-type":[{"value":"1559-0283","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]},"assertion":[{"value":"4 May 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}