Identification of amentoflavone as a potent SARS-CoV-2 M^pro inhibitor: a combination of computational studies and in vitro biological evaluation

References

• Adams, R., & Yuan, H. C. (1933). The stereochemistry of diphenyls and analogous compounds. Chemical Reviews, 12(2), 261–338.
   Google Scholar
• Alesawy, M. S., Abdallah, A. E., Taghour, M. S., Elkaeed, E. B., Eissa, I. H., & Metwaly, A. M. (2021). In silico studies of some isoflavonoids as potential candidates against COVID-19 targeting human ACE2 (hACE2) and viral main protease (Mpro). Molecules, 26, 2806.
   PubMed Web of Science ®Google Scholar
• Alothaid, H., Aldughaim, M. SK., El Bakkouri, K., Mashhadi, SA., & Al-Qahtani, A. A. (2020). Similarities between the effect of SARS-CoV-2 and HCV on the Cellular level, and the possible role of ion channels in COVID19 progression: A review of potential targets for diagnosis and treatment. Channels, 14(1), 403–412.
   PubMed Web of Science ®Google Scholar
• Armen, R., Alonso, D. O., & Daggett, V. (2003). The role of α-, 310-, and π-helix in helix→coil transitions. Protein Science: A Publication of the Protein Society, 12(6), 1145–1157. https://doi.org/10.1110/ps.0240103
   PubMed Web of Science ®Google Scholar
• Barco, A., Feduchi, E., & Carrasco, L. (2000). Poliovirus protease 3Cpro kills cells by apoptosis. Apoptosis: An International Journal on Programmed Cell Death, 266(3), 513–524.
   Google Scholar
• Basilaia, M., Chen, M. H., Secka, J., & Gustafson, J. L. (2022). Atropisomerism in the pharmaceutically relevant realm. Accounts of Chemical Research, 55(20), 2904–2919.
   PubMed Web of Science ®Google Scholar
• Bauer, P., Hess, B., & Lindahl, E. (2022). GROMACS. Source code.
   Google Scholar
• Besler, B. H., Merz, K. M., & Kollman, P. A. (1990). Atomic charges derived from semiempirical methods. Journal of Computational Chemistry, 11(4), 431–439. https://doi.org/10.1002/jcc.540110404
   Web of Science ®Google Scholar
• Bhattacharya, P., Abualnaza, K. M, & Javed, S. (2023). Theoretical studies, spectroscopic investigation, molecular docking, molecular dynamics and MMGBSA calculations with 2‐hydrazinoquinoline, Journal of Molecular Structure, 1274, 134482.
   Web of Science ®Google Scholar
• Bian, L., Gao, F., Zhang, J., He, Q., Mao, Q., Xu, M., & Liang, Z. (2021). Effects of SARS-CoV-2 variants on vaccine efficacy and response strategies. Expert Review of Vaccines, 20, 365–373. https://doi.org/10.1016/j.ijantimicag.2020.105948
   PubMed Web of Science ®Google Scholar
• Birt, D. F., Hendrich, S., & Wang, W. (2001). Dietary agents in cancer prevention: Flavonoids and isoflavonoids. Pharmacology & Therapeutics, 90, 157–177. https://doi.org/10.1016/S1360-1385(99)01471-5
   PubMed Web of Science ®Google Scholar
• Blanco, R., Carrasco, L., & Ventoso, I. (2003). Cell killing by HIV-1 protease. Journal of Biological Chemistry, 278, 1086–1093.
   PubMed Web of Science ®Google Scholar
• Bringmann, G., Gulder, T., Gulder, T. A. M., & Breuning, M. (2010). Atroposelective total synthesis of axially chiral biaryl natural products. Chemical Reviews, 111, 563–639.
   Google Scholar
• Bringmann, G., Price Mortimer, A. J., Keller, P. A., Gresser, M. J., Garner, J., & Breuning, M. (2005). Atroposelective synthesis of axially chiral biaryl compounds. Angewandte Chemie International Edition, 44, 5384–5427.
   Google Scholar
• Case, D. A., Aktulga, H. M., Belfon, K., Ben-Shalom, I. Y., Brozell, S. R., Cerutti, D. S., Cheatham, T. E. III, Cisneros, C. A., Cruzeiro, V. WD., Darden, T. A., Duke, R. E., Giambasu, G., Gilson, M. K., Gohlke, H., Goetz, A. W., Harris, R., Izadi, S. A., Izmailov, S. A., Jin, C., … Kollman, P. A. (2021). Amber 2021. University of California. https://doi.org/10.3389/fmolb.2017.00087
   Google Scholar
• Chau, D. H. W., Yuan, J., Zhang, H., Cheung, P., Lim, T., Liu, Z., Sall, A., & Yang, D. (2007). Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage of eIF4GI but not DAP5/p97/NAT1. Apoptosis, 12, 513–524. https://doi.org/10.1007/s10495-006-0013-0
   PubMed Web of Science ®Google Scholar
• Chavda, V. P., Vuppu, S., Mishra, T., Kamaraj, S., Patel, A. B., Sharma N., & Chen, Z.-S. (2022). Recent review of COVID-19 management: Diagnosis, treatment and vaccination. Pharmacological Reports, 74, 1120–1148.
   PubMed Web of Science ®Google Scholar
• Cho, E., Rosa, M., Anjum, R., Mehmood, S., Soban, M., Mujtaba, M., Bux, K., Moin, S. T., Tanweer, M., Dantu, S., Pandini, A., Yin, J., Ma, H., Ramanathan, A., Islam, B., Mey, A., Bhowmik, D., & Haider, S. (2021). Dynamic profiling of β-coronavirus 3CL Mpro protease ligand-binding sites. Journal of Chemical Information and Modeling, 61, 3058–3073.
   PubMed Web of Science ®Google Scholar
• Citarella, A., Scala, A., Piperno, A., & Micale, N. (2021). SARS-CoV-2 Mpro: A potential target for peptidomimetics and small-molecule inhibitors, Biomolecules, 11, 607.
   PubMed Web of Science ®Google Scholar
• Coelho, A. C., & Díez, J. G. (2015). Biological risks and laboratory-acquired infections: A reality that cannot be ignored in health biotechnology. Frontiers in Bioengineering and Biotechnology, 3, 56. https://doi.org/10.3389/fbioe.2015.00056
   PubMed Web of Science ®Google Scholar
• Cooley, R. B., Arp, D. J., & Karplus, P. A. (2010). Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices that enhance protein functionality. Journal of Molecular Biology, 404(2), 232–246. https://doi.org/10.1016/j.jmb.2010.09.034
   PubMed Web of Science ®Google Scholar
• Cucinotta D., & Vanelli, M. (2020). WHO declares COVID-19 a pandemic. Acta Biomedica, 91, 157–160.
   PubMedGoogle Scholar
• Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. The Journal of Chemical Physics, 98(12), 10089–10092. https://doi.org/10.1063/1.464397
   Web of Science ®Google Scholar
• Das, A., & Mukhopadhyay, C. (2007). Application of principal component analysis in protein unfolding: An all-atom molecular dynamics simulation study. The Journal of Chemical Physics, 127, 165103.
   PubMed Web of Science ®Google Scholar
• David, C. C., & Jacobs, D. J. (2014). Principal component analysis: A method for determining the essential dynamics of proteins. Methods in Molecular Biology, 1084, 193–226.
   PubMedGoogle Scholar
• Debnath, P., Bhaumik, S., Sen, D., Muttineni, R. K., & Debnath, S. (2021). Identification of SARS-CoV-2 main protease inhibitors using structure based virtual screening and molecular dynamics simulation of DrugBank Database. ChemistrySelect, 6(20), 4991–5013. https://doi.org/10.1002/slct.202100854
   PubMed Web of Science ®Google Scholar
• Delgado, L., Heckmann, C. M., Di Pisa, F., Gourlay, L., & Paradisi, F. (2021). Release of soybean isoflavones by using a β-glucosidase from Alicyclobacillus herbarius. Chembiochem: A European Journal of Chemical Biology, 22(7), 1223–1231. https://doi.org/10.1002/cbic.202000688
   PubMed Web of Science ®Google Scholar
• Dey, D., Hossain, R., Biswas, P., Paul, P., Islam, M.A., Ema, T. I., Gain, B. K., Hasan, M. M., Bibi, S., Islam, M. T., Rahman, Md. A., & Kim, B. (2022). Amentoflavone derivatives significantly act towards the main protease (3CLPRO/MPRO) of SARS-CoV-2: In silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology. Molecular Diversity, 2, 857–871.
   Google Scholar
• Dill, K. A., & Chan, H. S. (1997). From levinthal to pathways to funnels: The “new view” of protein folding kinetics. Nature Structural Biology, 4, 10–19.
   PubMedGoogle Scholar
• Dixon, R. A., & Pasinetti, G. M. (2010). Flavonoids and isoflavonoids: From plant biology to agriculture and neuroscience. Plant Physiology, 154, 453–457.
   PubMed Web of Science ®Google Scholar
• Dixon, R. A., & Steele, C. L. (1999). Flavonoids and isoflavonoids – A gold mine for metabolic engineering. Trends in Plant Science, 4(10), 394–400.
   PubMed Web of Science ®Google Scholar
• Eberhardt, J., Santos-Martins, D., Tillack, A. F., & Forli, S. (2021). AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. Journal of Chemical Information and Modeling, 61(8), 3891–3898.
   PubMed Web of Science ®Google Scholar
• Eliel, E. L., Wilen, S. H., & Mander, L. N. (1994). Stereochemistry of organic compounds (pp. 1122–1153). John Wiley & Sons.
   Google Scholar
• Faheem, B. K., Kumar, K., Sekhar, S., Kunjiappan, J., Jamalis, R., Balana-Fouce, B. K., Tekwani, & Sankaranarayanan, M. (2020). Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19. Bioorganic Chemistry, 104, 104269.
   PubMed Web of Science ®Google Scholar
• Feoktistova, M., Geserick, P., & Leverkus, M. (2016). Crystal violet assay for determining viability of cultured cells. Cold Spring Harbor Protocols.
   Google Scholar
• Ganta, K. K., Mandal, A., Debnath, S., Hazra, B., & Chaubey, B. (2017). Anti-HCV activity from semi-purified methanolic root extracts of Valeriana wallichii. Phytotherapy Research: PTR, 31(3), 433–440. https://doi.org/10.1002/ptr.5765
   PubMed Web of Science ®Google Scholar
• Gasteiger, J., & Marsili, M. (1978). A new model for calculating atomic charges in molecules. Tetrahedron Letters, 19(34), 3181–3184. https://doi.org/10.1016/S0040-4039(01)94977-9
   Google Scholar
• Genheden, S., & Ryde, U. (2015). The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opinion on Drug Discovery, 10, 449–461.
   PubMed Web of Science ®Google Scholar
• Ghosh, A. K., Mishevich, J. L., Mesecar A., & Mitsuya, H. (2022). Recent drug development and medicinal chemistry approaches for the treatment of SARS-CoV-2 infection and COVID-19. ChemMedChem, 17, e202200440.
   PubMed Web of Science ®Google Scholar
• Gil, C., Ginex, T., Maestro, I., Nozal, V., Barrado-Gil, L., Cuesta-Geijo, M. A., Urquiza, J., Ramirez, D., Alonso, C., Campillo, N. E., & Martinez, A. (2020). COVID-19: Drug targets and potential treatments Journal of Medicinal Chemistry, 63(21), 12359–12386.
   PubMed Web of Science ®Google Scholar
• Glunz, P. W. (2018). Recent encounters with atropisomerism in drug discovery. Bioorganic & Medicinal Chemistry Letters, 28, 53–60.
   PubMed Web of Science ®Google Scholar
• Gontijo, V. S., dos Santos, M. H., & Viegas, C. (2017). Biological and chemical aspects of natural biflavonoids from plants: A brief review. Mini-Reviews in Medicinal Chemistry, 17, 834–862.
   PubMed Web of Science ®Google Scholar
• Han, R. M., Tian, Y. X., Liu, Y., Chen, C. H., Ai, X. C., Zhang, J. P., & Skibsted, L. H. (2009). Comparison of flavonoids and isoflavonoids as antioxidants. Journal of Agricultural and Food Chemistry, 57, 3780–3785.
   PubMed Web of Science ®Google Scholar
• Hardenbrook, N. J., & Zhang, P. (2022). A structural view of the SARS-CoV-2 virus and its assembly. Current Opinion in Virology, 52, 123–134.
   PubMed Web of Science ®Google Scholar
• Harju, M., & Haglund, P. (1999). Determination of the rotational energy barriers of atropisomeric polychlorinated biphenyls, Fresenius' Journal of Analytical Chemistry, 364, 219–223.
   Google Scholar
• Hayward, S., & de Groot, B. L. (2008). Normal modes and essential dynamics. Methods in Molecular Biology, 443, 89–106.
   Google Scholar
• Hirsch, D. R., Metrano, A. J., Stone, E. A., Storch, G., Miller, S. J., & Murelli, R. P. (2019). Troponoid atropisomerism: Studies on the configurational stability of tropone-amide chiral axes, Organic Letters, 21(7), 2412–2415.
   PubMed Web of Science ®Google Scholar
• Hollingsworth, S. A., & Dror, R. O. (2018). Molecular dynamics simulation for all. Neuron, 99, 1129–1143.
   PubMed Web of Science ®Google Scholar
• Huff, S., Kummetha, I. R., Tiwari, S. K., Huante, M. B., Clark, A. E., Wang, S., Bray, W., Smith, D., Carlin, A. F., Endsley, M., & Rana, T. M. (2022). Discovery and mechanisms of SARS-CoV-2 main protease inhibitors, Journal of Medicinal Chemistry, 65, 2866–2879. https://doi.org/10.1021/acs.jmedchem.1c00566
   PubMedGoogle Scholar
• Hu, B., Guo, H., Zhou, P., & Shi, Z.-L. (2021). Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology, 19, 141–154.
   PubMed Web of Science ®Google Scholar
• Hu, Q., Xiong, Y., Zhu, G.-H., Zhang, Y.-N., Zhang, Y.-W., Huang, P., & Ge, G.-B. (2022). The SARS-CoV-2 main protease (Mpro): Structure, function, and emerging therapies for COVID-19, Journal of Medicinal Chemistry, 3(4), e151.
   Google Scholar
• Huang, J., & MacKerell, A. D. (2013). CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR Data. Journal of Computational Chemistry, 34(25), 2135–2145. https://doi.org/10.1002/jcc.23354
   PubMed Web of Science ®Google Scholar
• Idrees, M., Khan, S., Memon, N. H., & Zhang, Z. (2021). Effect of the phytochemical agents against the SARS-CoV and some of them selected for application to COVID-19: A mini-review. Current Pharmaceutical Biotechnology, 22, 444–450. https://doi.org/10.3390/molecules28062735
   PubMed Web of Science ®Google Scholar
• Illanes-Álvarez, F., Márquez-Ruiz, D., Márquez-Coello, M., Cuesta-Sancho, S., & Girón-González, J. (2021). A. Similarities and differences between HIV and SARS-CoV-2. International Journal of Medical Sciences, 18, 846–851. https://doi.org/10.1080/19336950.2020.1837439
   PubMed Web of Science ®Google Scholar
• Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., Li, X., Zhang, L., Peng, C., Duan, Y., Yu, J., Wang, L., Yang, K., Liu, F., Rendi, J., Yang, X., You, T., Liu, X., …, Yang, H. (2020). Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 582, 289–293. https://doi.org/10.1073/pnas.2117142119
   PubMed Web of Science ®Google Scholar
• Jo, S., Kim, S., Shin, D. H,. & Kim, M. S. (2020). Inhibition of SARSCoV 3CL protease by flavonoids. Journal of Enzyme Inhibition and Medicinal Chemistry, 35, 145–151.
   PubMed Web of Science ®Google Scholar
• Jolliffe, I. T., & Cadima, J. (2016). Principal component analysis: A review and recent developments. Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences, 374(2065), 20150202. https://doi.org/10.1098/rsta.2015.0202
   PubMed Web of Science ®Google Scholar
• Justino, G. C., Nascimento, C. P., & Justino, M. C. (2021). Molecular dynamics simulations and analysis for bioinformatics undergraduate students. Biochemistry and Molecular Biology Education, 49(4), 570–582. https://doi.org/10.1002/bmb.21512
   PubMed Web of Science ®Google Scholar
• Kikuta, S. (2020). The cytotoxic effect of genistein, a soybean isoflavone, against cultured tribolium cells. Insects, 11(4), 241. https://doi.org/10.3390/insects11040241
   PubMed Web of Science ®Google Scholar
• Klotz, L. C., & Sylvester, E. J. (2014). The consequences of a lab escape of a potential pandemic pathogen. Frontiers in Public Health, 2, 116.
   PubMedGoogle Scholar
• Kopustinskiene, D. M., Jakstas, V., Savickas, A., & Bernatoniene, J. (2020). Flavonoids as anticancer agents. Nutrients, 12, 457.
   Google Scholar
• Krishnamoorthy, S., Swain, B., Verma, R. S., & Gunthe, S. S. (2020). SARS CoV, MERS-CoV, and 2019-nCoV viruses: An overview of origin, evolution, and genetic variations. Virus Disease, 31, 411–423. https://doi.org/10.1038/s41586-020-2008-3
   PubMedGoogle Scholar
• Kumarasamy, E., Raghunathan, R., Sibi, M. P., & Sivaguru, J. (2015). Nonbiaryl and heterobiaryl atropisomers: Molecular templates with promise for atropselective chemical transformations. Chemical Reviews, 115, 11239–11300.
   Google Scholar
• Kwok, S. C., Mant, C. T., & Hodges, R. S. (2002). Importance of secondary structural specificity determinants in protein folding: Insertion of a native β-sheet sequence into an α-helical coiled-coil. Protein Science: A Publication of the Protein Society, 11(6), 1519–1531. https://doi.org/10.1110/ps.4170102
   PubMed Web of Science ®Google Scholar
• LapPlante, S. R., Edwards, P. J., Fader, L. D., Jakalian, A., & Hucke, O. (2011). Revealing atropisomer axial chirality in drug discovery. ChemMedChem, 6, 505–513.
   PubMed Web of Science ®Google Scholar
• Lee, E., Shin, S., Lee, J.-Y., Lee, S., Kim, J.-K., Yoon, D.-Y., Woo, E.-R., & Kim, Y. (2012). Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisome proliferator-activated receptor γ activation. Bulletin of the Korean Chemical Society, 33(7), 2219–2223. https://doi.org/10.5012/bkcs.2012.33.7.2219
   Web of Science ®Google Scholar
• Lei, S., Chen, X., Wu, J., Duan X., & Men, K. (2022). Small molecules in the treatment of COVID-19. Signal Transduction and Targeted Therapy, 7, 387.
   PubMed Web of Science ®Google Scholar
• Liu, M., Liang, Z., Cheng, Z. J., Liu, L., Liu, Q., Mai, M., Chen, H., Lei, B., Yu, S., Chen, H., Zheng, P., & Sun, B. (2023). SARS-CoV-2 neutralising antibody therapies: Recent advances and future challenges. Reviews in Medical Virology, e2464.
   PubMed Web of Science ®Google Scholar
• Liu, S., Abboud, M., Mikhailov, V., Liu, X., Reinbold, R., & Schofield, C. J. (2023). Differentiating inhibition selectivity and binding affinity of isocitrate dehydrogenase 1 variant inhibitors. Journal of Medicinal Chemistry, 66(7), 5279–5288. https://doi.org/10.1021/acs.jmedchem.3c00203
   PubMed Web of Science ®Google Scholar
• Maisuradze, G. G., Liwo, A., & Scheraga, H. A. (2010). Relation between free energy landscapes of proteins and dynamics. Journal of Chemical Theory and Computation, 6, 583–595.
   PubMed Web of Science ®Google Scholar
• Maisuradze, G. G., Liwo, A., & Scheraga, H. A. (2009). Principal component analysis for protein folding dynamics. Journal of Molecular Biology, 385, 312–329.
   PubMed Web of Science ®Google Scholar
• Mandal, A., Biswas, D., & Hazra, B. (2021). Natural products from plants with prospective anti-HIV activity and relevant mechanisms of action. In Studies in natural products chemistry (Chapter 9, Vol. 66, pp. 225–271). Elsevier.
   Google Scholar
• Mandal, A., & Hazra, B. (2023). Medicinal plant molecules against hepatitis C virus: Current status and future prospect. Phytotherapy Research, 1–22. https://doi.org/10.1017/jns.2016.41
   Web of Science ®Google Scholar
• Mandal, A., Hazra, B., Prajapati, V. K., and Moundipa, P. F. (2022). Plant products for antiviral therapeutics, Frontiers in Pharmacology, 13, 1–4.
   Web of Science ®Google Scholar
• Mandal, A., Jha, A. K., & Hazra, B. (2021). Plant products as inhibitors of coronavirus 3CL protease, Frontiers in Pharmacology, 12, 1–16. https://doi.org/10.1016/j.bmcl.2020.127377
   Web of Science ®Google Scholar
• Mark, P., & Nilsson, L. (2001). Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K. The Journal of Physical Chemistry A, 105(43), 9954–9960. https://doi.org/10.1021/jp003020w
   Web of Science ®Google Scholar
• McCue, P., & Shetty, K. (2004). Health benefits of soy isoflavonoids and strategies for enhancement: A review. Critical Reviews in Food Science and Nutrition, 44, 361–367. https://doi.org/10.1080/10408690490509591
   PubMed Web of Science ®Google Scholar
• Meeko. (2023). https://github.com/forlilab/Meeko.
   Google Scholar
• Mereghetti, P., Riccardi, L., Brandsdal, B. O., Fantucci, P., Gioia, L. D., & Papaleo, E. (2010). Near native-state conformational landscape of psychrophilic and mesophilic enzymes: Probing the folding funnel model. The Journal of Physical Chemistry B, 114, 7609–7619.
   PubMed Web of Science ®Google Scholar
• Miadoková, E. (2004). Isoflavonoids—An overview of their biological activities and potential health benefits. Critical Reviews in Food Science and Nutrition, 2(5), 361–367.
   Google Scholar
• Monica, G. L., Bono, A., Lauria, A., & Martorana, A. (2022). Targeting SARSCoV-2 main protease for treatment of COVID-19: Covalent inhibitors structure-activity relationship insights and evolution perspectives. Journal of Medicinal Chemistry, 65, 12500–12534.
   PubMed Web of Science ®Google Scholar
• Moritsugu, K., Terada, T., & Kidera, A. (2017). Free-energy landscape of protein-ligand interactions coupled with protein structural changes. The Journal of Physical Chemistry B, 121(4), 731–740.
   PubMed Web of Science ®Google Scholar
• Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). Autodock4 and AutoDockTools4: Automated docking with selective receptor flexiblity. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256
   PubMed Web of Science ®Google Scholar
• Nose, S., & Klein, M. L. (1983). Constant pressure molecular dynamics for molecular systems. Molecular Physics, 50, 1055–1076. https://doi.org/10.1063/1.328693
   Web of Science ®Google Scholar
• Oki, M. (2007). Recent advances in atropisomerism. In N. L. Allinger, E. L. Eliel, & S. H. Wilen (Eds.), Topics in stereochemistry (Vol. 14, pp. 1–81). John Wiley & Sons, Inc.
   Google Scholar
• Onuchic, J. N., Schulten, Z. L., & Wolynes, P. G. (1997). Theory of protein folding: The energy landscape perspective. Annual Review of Physical Chemistry, 48, 545–600.
   PubMed Web of Science ®Google Scholar
• Osipiuk, J., Azizi, S. A., Dvorkin, S., Endres, M., Jedrzejczak, R., Jones, K. A., Kang, S., Kathayat, R. S., Kim, Y., Lisnyak, V. G., Maki, S. L., Nicolaescu, V., Taylor, C. A., Tesar, C., Zhang, Y.-A., Zhou, Z., Randall, G., Michalska, K., Snyder, S. A., …, Joachimiak, A. (2021). Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors. Nature Communications, 12(1), 743.
   PubMed Web of Science ®Google Scholar
• Panche, A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: An overview. Journal of Nutritional Science, 5, e47.
   PubMed Web of Science ®Google Scholar
• Papaleo, E., Mereghetti, P., Fantucci, P., Grandori, R., & De Gioia, L. (2009). Free-energy landscape, principal component analysis, and structural clustering to identify representative conformations from molecular dynamics simulations: The myoglobin case. Journal of Molecular Graphics and Modelling, 27, 889–899.
   PubMed Web of Science ®Google Scholar
• Park, H.-J., Park, J.-H., Moon, J.-O., Lee, K.-T., Jung, W.-T., Oh, S.-R., & Lee, H.-K. (1999). Isoflavone glycosides from the flowers of Pueraria thunbergiana. Phytochemistry, 51(1), 147–151. https://doi.org/10.1016/S0031-9422(98)00729-8
   Web of Science ®Google Scholar
• Parrinello, M., & Rahman, A. (1981). Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied Physics, 52(12), 7182–7190.
   Web of Science ®Google Scholar
• Patel, S., Sandha, K., Waingankar, A., Jain, P., & Abhyankar, A. (2023). Atropisomerism transforming anti-cancer drug discovery. Chemical Biology & Drug Design, 101, 138–157. https://doi.org/10.1021/acs.accounts.2c00500
   PubMed Web of Science ®Google Scholar
• Patel, D. C., Woods, R. M., Breitbach, Z. S., Berthod, A., & Armstrong, D. W. (2017). Thermal racemization of biaryl atropisomers. Tetrahedron: Asymmetry, 28, 1557–1561. https://doi.org/10.1021/acs.orglett.9b00707
   Google Scholar
• Pelter, M. W., Howell, M. T., Anderson, C., and Sayeed, A. (2020). Computational activity to visualize stereoisomers in molecules with an axis of chirality. Journal of Chemical Education, 97, 754–759.
   Web of Science ®Google Scholar
• Perreault, S., Chandrasekhar, J., & Patel, L. (2022). Atropisomerism in drug discovery: A medicinal chemistry perspective inspired by atropisomeric Class I PI3K inhibitors. Accounts of Chemical Research, 55, 2581–2593.
   PubMed Web of Science ®Google Scholar
• Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera–A visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25(13), 1605–1612. https://doi.org/10.1002/jcc.20084
   PubMed Web of Science ®Google Scholar
• Pietrucci, F. (2017). Strategies for the exploration of free energy landscapes: Unity in diversity and challenges ahead. Physical Review, 2, 32–45. https://doi.org/10.1021/acs.jpcb.6b11696
   Google Scholar
• Resnick, S. J., Iketani, S., Hong, S. J., Zask, A., Liu, H., Kim, S., Melore, S., Lin, F.-Y., Nair, M. S., Huang, Y., Lee, S., Tay, N. E. S., Rovis, T., Yang, H. W., Xing, L., Stockwell, B. R., Ho, D. D., & Chavez, A. (2021). Inhibitors of coronavirus 3CL proteases protect cells from protease-mediated cytotoxicity. Journal of Virology, 95(14), e0237420. https://doi.org/10.1128/JVI.02374-20
   PubMed Web of Science ®Google Scholar
• Riccardi, L., Nguyen, P. H., & Stock, G. (2012). Construction of the free energy landscape of peptide aggregation from molecular dynamics simulations. Journal of Chemical Theory and Computation, 8(4), 1471–1479.
   Google Scholar
• Rushton, G. T., Burns, W. G., Lavin, J. M., Chong, Y. S., Pellechia, P., & Shimizu, K. D. (2007). Determination of the rotational barrier for kinetically stable conformational isomers via NMR and 2D TLC, Journal of Chemical Education, 84, 1499.
   Google Scholar
• Sambrook, J., & Russell, D. W. (2001). Molecular cloning: A laboratory manual (3rd ed.). Cold Spring Harbor Laboratory Press.
   Google Scholar
• Sander, T., Freyss, J., von Korff, M., & Rufener, C. (2015). DataWarrior: An open-source program for chemistry aware data visualization and analysis. Journal of Chemical Information and Modeling, 55(2), 460–473. https://doi.org/10.1021/ci500588j
   PubMed Web of Science ®Google Scholar
• Santana, F. P. R., Thevenard, F., Gomes, K. S., Taguchi, L., Câmara, N. O. S., Stilhano, R. S., Ureshino, R. P., Prado C. M., and Lago, J. H. G. (2021). New perspectives on natural flavonoids on COVID-19- induced lung injuries. Phytotherapy Research, 35, 4988–5006.
   PubMed Web of Science ®Google Scholar
• Savi, C. D., Hughes D. L., & Kvaerno, L. (2020). Quest for a COVID-19 cure by repurposing small-molecule drugs: Mechanism of action, clinical development, synthesis at scale, and outlook for supply. Organic Process Research & Development, 24, 940–976.
   PubMed Web of Science ®Google Scholar
• Singh, A. V. (2021). Potential of amentoflavone with antiviral properties in COVID-19 treatment. Asian Biomedicine, 27, 153–159. https://doi.org/10.1007/s11030-022-10459-9
   Google Scholar
• Singh, U., & Kollman, C. (1984). An approach to computing electrostatic charges for molecules. Journal of Computational Chemistry, 5, 129–145.
   Web of Science ®Google Scholar
• Smith, D. E., Marquez, I., Lokensgard, M. E., Rheingold, A. L., Hecht, D. A., & Gustafson, J. L. (2015). Exploiting atropisomerism to increase the target selectivity of kinase inhibitors. Angewandte Chemie International Edition, 54, 11754–11759.
   PubMed Web of Science ®Google Scholar
• Smyth, J. E., Butler, N. M., & Keller, P. A. (2015). A twist of nature–the significance of atropisomers in biological systems. Natural Product Reports, 32, 1562–1583.
   PubMed Web of Science ®Google Scholar
• Sychrová, A., Koláriková, I., Žemlička, M., & Šmejkal, K. (2020). Natural compounds with dual antimicrobial and anti-inflammatory effects. Phytochemistry Reviews, 19, 1471–1502.
   Web of Science ®Google Scholar
• Talapatra, S. K., & Talapatra, B. (2015). Chemistry of plant natural products. Springer: Verlag Berlin Heidelberg. https://doi.org/10.1021/cr60042a003
   Google Scholar
• Toenjes, S. T., & Gustafson, J. L. (2018). Atropisomerism in medicinal chemistry: Challenges and opportunities. Future Medicinal Chemistry, 10, 409–422.
   PubMed Web of Science ®Google Scholar
• Toenjes, S. T., Heydari, B. S., Albright, S. T., Hazin, R., Ortiz, M. A., Piedrafita, F. J., & Gustafson, J. L. (2023). Controlling ibrutinib’s conformations about its heterobiaryl axis to increase BTK selectivity. ACS Medicinal Chemistry Letters, 14, 305–311.
   PubMed Web of Science ®Google Scholar
• Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31, 455–461. https://doi.org/10.1021/acs.jcim.1c00203
   Web of Science ®Google Scholar
• Ullah, A., Munir, S., Badshah, S. L., Khan, N., Ghani, L., Poulson, B. G., Emwas, A.-H., & Jaremko, M. (2020). Important flavonoids and their role as a therapeutic agent. Molecules, 25, 5243.
   Google Scholar
• Ullrich, S., & Nitsche, C. (2020). The SARS-CoV-2 main protease as drug target. Bioorganic & Medicinal Chemistry Letters, 30(17), 127377.
   PubMed Web of Science ®Google Scholar
• Ullrich, S., & Nitsche, C. (2022). SARS-CoV-2 papain-like protease: Structure, function and inhibition. ChemBioChem, 23, e202200327. https://doi.org/10.1038/s41467-021-21060-3
   PubMed Web of Science ®Google Scholar
• Valdés-Tresanco, M. S., Valdés-Tresanco, M. E., Valiente, P. A., & Moreno, E. (2021). gmx_MM-PBSA: A new tool to perform end-state free energy calculations with GROMACS. Journal of Chemical Theory and Computation, 17(10), 6281–6291. https://doi.org/10.1021/acs.jctc.1c00645
   PubMed Web of Science ®Google Scholar
• Wales, D. J. (2003). Energy landscapes. Cambridge University Press. https://doi.org/10.1021/ct200911w
   Google Scholar
• Wang, C., Greene, D., Xiao, L., Qi, R., & Luo, R. (2018). Recent developments and applications of the MM-PBSA method. Frontiers in Molecular Biosciences, 4, 87.
   PubMed Web of Science ®Google Scholar
• Wang, E., Sun, H., Wang, J., Wang, Z., Liu, H., Zhang, J. Z. H., & Hou, T. (2019). End-point binding free energy calculation with MM/PBSA and MM/GBSA: Strategies and applications in drug design. Chemical Reviews, 119(16), 9478–9508. https://doi.org/10.1021/acs.chemrev.9b00055
   PubMed Web of Science ®Google Scholar
• Wang, L., Wang, Y., Ye D., & Liu, Q. (2020). Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence. International Journal of Antimicrobial Agents, 55(6), 105948.
   PubMed Web of Science ®Google Scholar
• Wang, T., Li, Q., & Bi, K. (2018). Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian Journal of Pharmaceutical Sciences, 13, 12–23.
   PubMed Web of Science ®Google Scholar
• Wang, Z., Meng, L., Liu, X., Zhang, L., Yu, Z., & Wu, G. (2022). Recent progress toward developing axial chirality bioactive compounds. European Journal of Medicinal Chemistry, 243, 114700.
   Google Scholar
• WHO Coronavirus (COVID-19) Dashboard. (2023). https://covid19.who.int/
   Google Scholar
• Wu, C., Liu, Y., Yang, Y., Zhang, P., Zhong, W., Wang, Y., Wang, Q., Xu, Y., Li, M., Li, X., Zheng, M., Chen L., & Li, H. (2020). Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharmaceutica Sinica B, 10, 766–788. https://doi.org/10.1021/acs.jmedchem.0c00606
   PubMed Web of Science ®Google Scholar
• Wu, F., Zhao, S., Yu, B., Chen, Y. M., Wang, W., Song, Z. G., Hu, Y., Tao, Z. W., Tian, J. H., Pei, Y. Y., Yuan, M. L., Zhang, Y. L., Dai, F. H., Liu, Y., Wang, Q. M., Zheng, J. J., Xu, L., Holmes, E. C., & Zhang, Y. Z. (2020). A new coronavirus associated with human respiratory disease in China. Nature, 579(7798), 265–269.
   PubMed Web of Science ®Google Scholar
• Wu, J.-Y., Wang, T.-Y., Ding, H.-Y., Lee, C.-C., & Chang, T.-S. (2022). A novel soy isoflavone derivative, 3′-hydroxyglycitin, with potent antioxidant and anti-α-glucosidase activity. Plants, 11(17), 2202. https://doi.org/10.3390/plants11172202
   Google Scholar
• Xiong, X., Tang, N., Lai, X., Zhang, J., Wen, W., Li, X., Li, A., Wu, Y., & Liu, Z. (2021). Insights into amentoflavone: A natural multifunctional biflavonoid. Frontiers in Pharmacology, 12, 768708. https://doi.org/10.3389/fphar.2021.768708
   PubMed Web of Science ®Google Scholar
• Yan, W., Zheng, Y., Zeng, X., He B., & Cheng, W. (2022). Structural biology of SARS-CoV-2: Open the door for novel therapies. Signal Transduction and Targeted Therapy, 7.
   Web of Science ®Google Scholar
• Yang, H., & Rao, Z. (2021). Structural biology of SARS-CoV-2 and implications for therapeutic development. Nature Reviews Microbiology, 19, 685–700.
   PubMed Web of Science ®Google Scholar
• Yang, Y. D., Yang, B. B., & Li, L. (2022). A nonneglectable stereochemical factor in drug development: Atropisomerism. Chirality, 34, 1355–1370.
   PubMed Web of Science ®Google Scholar
• Yang, J. Y., Ma, Y. X., Liu, Y., Peng, X. J., & Chen, X. Z. (2023). A comprehensive review of natural flavonoids with anti-SARS-CoV-2 activity. Molecules, 28(6), 2735.
   Google Scholar
• Yea, J. & Ma, S. (2014). Conquering three-carbon axial chirality of allenes. Organic Chemistry Frontiers, 1, 1210–1224.
   Web of Science ®Google Scholar
• Yoshino, R., Yasuo, N., & Sekijima, M. (2020). Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates. Scientific Reports, 10, 1–8.
   PubMed Web of Science ®Google Scholar
• Yu, S., Yan, H., Zhang, L., Shan, M., Chen, P., Ding, A., & Li, S. F. Y. (2017). A review on the phytochemistry, pharmacology, and pharmacokinetics of amentoflavone, a naturally-occurring biflavonoid. Molecules, 22(2), 299.
   PubMed Web of Science ®Google Scholar
• Yuan, Y., Jiao, B., Qu, L., Yang D., & Liu, R. (2023). The development of COVID-19 treatment. Frontiers in Immunology, 14, 1125246.
   PubMedGoogle Scholar
• Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L., Becker, S., Rox, K., & Hilgenfeld, R. (2020). Crystal structure SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 368(6489), 409–412. https://doi.org/10.1126/science.abb3405
   PubMed Web of Science ®Google Scholar
• Zhao, Y., Zhu, Y., Liu, X., Jin, Z., Duan, Y., Zhang, Q., Wu, C., Feng, L., Du, X., Zhao, J., Shao, M., Zhang, B., Yang, X., Wu, L., Ji, X., Guddat, L.W., Yang, K., Rao, Z., & Yang, H. (2022). Structural basis for replicase polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2. Proceedings of the National Academy of Sciences of the United States of America, 119(16), e2117142119.
   PubMed Web of Science ®Google Scholar
• Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W., Si, H. R., Zhu, Y., Li, B., Huang, C. L., Chen, H. D., Chen, J., Luo, Y., Guo, H., Jiang, R. D., Liu, M. Q., Chen, Y., Shen, X. R., Wang, X., …, Shi, Z. L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature579, 270–273.
   PubMed Web of Science ®Google Scholar
• Zoete, V., Cuendet, M. A., Grosdidier, A., & Michielin, O. (2011). SwissParam: A fast force field generation tool for small organic molecules. Journal of Computational Chemistry, 32(11), 2359–2368. https://doi.org/10.1002/jcc.21816
   PubMed Web of Science ®Google Scholar