Fourteen immunomodulatory alkaloids and two prenylated phenylpropanoids with dual therapeutic approach for COVID-19: molecular docking and dynamics studies

References

• Abd El-Salam, M. J., Mekky, H., El-Naggar, E.M.B., Ghareeb, D., El-Demellawy, M., & El-Fiky, F. (2015). Hepatoprotective properties and biotransformation of berberine and berberrubine by cell suspension cultures of Dodonaea viscosa and Ocimum basilicum. South African Journal of Botany, 97, 191–195. https://doi.org/10.1016/j.sajb.2015.01.005
   Web of Science ®Google Scholar
• Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., & Lindahl, E. (2015). GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1–2, 19–25. https://doi.org/10.1016/j.softx.2015.06.001
   Google Scholar
• Ahmed, B., Ali Ashfaq, U., & Usman Mirza, M. J. N. P. R. (2018). Medicinal plant phytochemicals and their inhibitory activities against pancreatic lipase: Molecular docking combined with molecular dynamics simulation approach. Natural Product Research, 32(10), 1123–1129. https://doi.org/10.1080/14786419.2017.1320786
   PubMed Web of Science ®Google Scholar
• Alamri, M. A., Tahir Ul Qamar, M., Mirza, M. U., Bhadane, R., Alqahtani, S. M., Muneer, I., Froeyen, M., & Salo-Ahen, O. M. H. (2021). Pharmacoinformatics and molecular dynamics simulation studies reveal potential covalent and FDA-approved inhibitors of SARS-CoV-2 main protease 3CLpro. Journal of Biomolecular Structure & Dynamics, 39(13), 4936–4948. https://doi.org/10.1080/07391102.2020.1782768
   PubMed Web of Science ®Google Scholar
• Amin, S., Banerjee, S., Singh, S., Qureshi, I. A., Gayen, S., & Jha, T. J. M. D. (2021). First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: An endeavor on COVID-19 drug discovery. Molecular Diversity, 25(3), 1827–1838. https://doi.org/10.1007/s11030-020-10166-3
   PubMed Web of Science ®Google Scholar
• Amirkia, V., & Heinrich, M. J. P. L. (2014). Alkaloids as drug leads – A predictive structural and biodiversity-based analysis. Phytochemistry Letters, 10, xlviii–xlliii. https://doi.org/10.1016/j.phytol.2014.06.015
   Web of Science ®Google Scholar
• Anand, K., Ziebuhr, J., Wadhwani, P., Mesters, J. R., & Hilgenfeld, R. J. S. (2003). Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science (New York, N.Y.), 300(5626), 1763–1767. https://doi.org/10.1126/science.1085658
   PubMed Web of Science ®Google Scholar
• Anand, M., & Basavaraju, R. (2021). A review on phytochemistry and pharmacological uses of Tecoma stans (L.) Juss. ex Kunth. Journal of Ethnopharmacology, 265, 113270. https://doi.org/10.1016/j.jep.2020.113270
   Google Scholar
• Andrade, P. B., Valentão, P., & Pereira, D. M. (2017). Natural products targeting clinically relevant enzymes. John Wiley & Sons.
   Google Scholar
• Baglivo, M., Baronio, M., Natalini, G., Beccari, T., Chiurazzi, P., Fulcheri, E., Petralia, P., Michelini, S., Fiorentini, G., Miggiano, G. A., Morresi, A., Tonini, G., & Bertelli, M. (2020). Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: A possible strategy for reducing SARS-COV-2 infectivity?. Acta Biomedica, 91, 161. https://doi.org/10.23750/abm.v91i1.9402
   Google Scholar
• Barbera, N., Ayee, M. A. A., Akpa, B. S., & Levitan, I. (2018). Molecular dynamics simulations of Kir2.2 interactions with an ensemble of cholesterol molecules. Biophysical Journal, 115(7), 1264–1280. https://doi.org/10.1016/j.bpj.2018.07.041
   PubMed Web of Science ®Google Scholar
• Barceloux, D. G. J. D.-A.-M. (2009). Pepper and capsaicin (capsicum and piper species). Disease-a-Month: DM, 55(6), 380–390. https://doi.org/10.1016/j.disamonth.2009.03.008
   PubMedGoogle Scholar
• Batool, F., Mughal, E. U., Zia, K., Sadiq, A., Naeem, N., Javid, A., Ul-Haq, Z., & Saeed, M. (2022). Synthetic flavonoids as potential antiviral agents against SARS-CoV-2 main protease. Journal of Biomolecular Structure & Dynamics, 40(8), 3777–3788. https://doi.org/10.1080/07391102.2020.1850359
   PubMed Web of Science ®Google Scholar
• Berretta, A. A., Arruda, C., Miguel, F. G., Baptista, N., Nascimento, A. P., Marquele-Oliveira, F., Hori, J. I., Barud, H., Damaso, B., Ramos, C. J. S., Ferreira, R., & Bastos, J. K. (2017). Functional properties of Brazilian propolis: From chemical composition until the market (pp. 55–98). InTechOpen.
   Google Scholar
• Beserra, F. P., Gushiken, L. F. S., Hussni, M. F., Ribeiro, V. P., Bonamin, F., Jackson, C. J., Pellizzon, C. H., & Bastos, J. K. J. P. R. (2021). Artepillin C as an outstanding phenolic compound of Brazilian green propolis for disease treatment: A review on pharmacological aspects. Phytotherapy Research, 35(5), 2274–2286. https://doi.org/10.1002/ptr.6875
   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(4), 607. https://doi.org/10.3390/biom11040607
   PubMed Web of Science ®Google Scholar
• Coelho, G. R., Mendonça, R. Z., Vilar, K. d. S., Figueiredo, C. A., Badari, J. C., Taniwaki, N., Namiyama, G., Oliveira, M. I. d., Curti, S. P., Evelyn Silva, P., & Negri, G. (2015). Antiviral action of hydromethanolic extract of geopropolis from Scaptotrigona postica against antiherpes simplex virus (HSV). Evidence-Based Complementary and Alternative Medicine, 2015, 1–10.2015. https://doi.org/10.1155/2015/296086
   Web of Science ®Google Scholar
• Corbeil, C. R., Williams, C. I., & Labute, P. (2012). Variability in docking success rates due to dataset preparation. Journal of Computer-Aided Molecular Design, 26(6), 775–786. https://doi.org/10.1007/s10822-012-9570-1
   PubMed Web of Science ®Google Scholar
• Cordell, G. A., Quinn‐beattie, M. L., & Farnsworth, N. R. (2001). The potential of alkaloids in drug discovery. Phytotherapy Research: PTR, 15(3), 183–205. https://doi.org/10.1002/ptr.890
   PubMed Web of Science ®Google Scholar
• de Barros, M. P., Sousa, J. P. B., Bastos, J. K., & de Andrade, S. F. (2007). Effect of Brazilian green propolis on experimental gastric ulcers in rats. Journal of Ethnopharmacology, 110(3), 567–571. https://doi.org/10.1016/j.jep.2006.10.022
   PubMed Web of Science ®Google Scholar
• Ferreira, J. C., Fadl, S., Villanueva, A. J., & Rabeh, W. M. (2021a). Catalytic dyad residues His41 and Cys145 impact the catalytic activity and overall conformational fold of the main SARS-CoV-2 protease 3-chymotrypsin-like protease. Frontiers in Chemistry 9, 491. https://doi.org/10.3389/fchem.2021.692168
   Google Scholar
• Ferreira, J. C., & Rabeh, W. M. (2020). Biochemical and biophysical characterization of the main protease, 3-chymotrypsin-like protease (3CLpro) from the novel coronavirus SARS-CoV 2. Scientific Reports, 10, 1–10. https://doi.org/10.1038/s41598-020-79357-0
   Google Scholar
• Ferreira, J. C., Reis, M. B., Coelho, G. D. P., Gastaldello, G. H., Peti, A. P. F., Rodrigues, D. M., Bastos, J. K., Campo, V. L., Sorgi, C. A., Faccioli, L. H., Gardinassi, L. G., Tefé-Silva, C., & Zoccal, K. F. (2021b). Baccharin and p-coumaric acid from green propolis mitigate inflammation by modulating the production of cytokines and eicosanoids. Journal of Ethnopharmacology, 278, 114255. https://doi.org/10.1016/j.jep.2021.114255
   PubMed Web of Science ®Google Scholar
• Fielding, B. C., da Silva Maia Bezerra Filho, C., Ismail, N. S. M., & de Sousa, D. P. (2020). Alkaloids: Therapeutic potential against human coronaviruses. Molecules, 25(23), 5496. https://doi.org/10.3390/molecules25235496
   PubMed Web of Science ®Google Scholar
• Fu, L., Ye, F., Feng, Y., Yu, F., Wang, Q., Wu, Y., Zhao, C., Sun, H., Huang, B., Niu, P., Song, H., Shi, Y., Li, X., Tan, W., Qi, J., & Gao, G. F. (2020). Both boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease. Nature Communications, 11(1), 4417. https://doi.org/10.1038/s41467-020-18233-x
   PubMed Web of Science ®Google Scholar
• Gentile, D., Patamia, V., Scala, A., Sciortino, M. T., Piperno, A., & Rescifina, A. J. M. D. (2020). Putative inhibitors of SARS-CoV-2 main protease from a library of marine natural products: A virtual screening and molecular modeling study. Marine Drugs, 18(4), 225. https://doi.org/10.3390/md18040225
   PubMed Web of Science ®Google Scholar
• Grüter, T., Blusch, A., Motte, J., Sgodzai, M., Bachir, H., Klimas, R., Ambrosius, B., Gold, R., Ellrichmann, G., & Pitarokoili, K. J. J. O. N. (2020). Immunomodulatory and anti-oxidative effect of the direct trpv1 receptor agonist capsaicin on Schwann cells. Neuroinflammation, 17, 1–16. https://doi.org/10.1186/s12974-020-01821-5
   Google Scholar
• Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2), 271–280.e8. https://doi.org/10.1016/j.cell.2020.02.052
   PubMed Web of Science ®Google Scholar
• Horrigan, L. A., Kelly, J. P., & Connor, T. J. (2006). Immunomodulatory effects of caffeine: Friend or foe? Pharmacology & Therapeutics, 111(3), 877–892. https://doi.org/10.1016/j.pharmthera.2006.02.002
   PubMed Web of Science ®Google Scholar
• Huang, J., Rauscher, S., Nawrocki, G., Ran, T., Feig, M., DE Groot, B. L., Grubmüller, H., & Mackerell, A. D., Jr. (2017). CHARMM36m: An improved force field for folded and intrinsically disordered proteins. Nature Methods, 14(1), 71–73. https://doi.org/10.1038/nmeth.4067
   PubMed Web of Science ®Google Scholar
• Ibrahim, M. A., Abdeljawaad, K. A., Abdelrahman, A. H., & Hegazy, M.-E. F. (2021). Natural-like products as potential SARS-CoV-2 Mpro inhibitors: In-silico drug discovery. Journal of Biomolecular Structure & Dynamics, 39(15), 5722–5734. https://doi.org/10.1080/07391102.2020.1790037
   PubMed Web of Science ®Google Scholar
• Iqbal, N., Adhikari, A., Kanwal, N., Abdalla, O. M., Mesaik, M. A., & Musharraf, S. G. (2015). New immunomodulatory steroidal alkaloids from Sarcococa saligna. Phytochemistry Letters, 14, 203–208. https://doi.org/10.1016/j.phytol.2015.10.009
   Web of Science ®Google Scholar
• Israelachvili, J. N. (2011). Intermolecular and surface forces (Rev. 3rd ed.). Elsevier Science.
   Google Scholar
• Jantan, I., Ahmad, W., & Bukhari, S. N. A. (2015). Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials. Frontiers in Plant Sciences, 6, 655. https://doi.org/10.3389/fpls.2018.01178
   Google Scholar
• Jo, S., Kim, T., Iyer, V. G., & Im, W. (2008). CHARMM‐GUI: A web‐based graphical user interface for CHARMM. Journal of Computational Chemistry, 29(11), 1859–1865. https://doi.org/10.1002/jcc.20945
   PubMed Web of Science ®Google Scholar
• Kalmarzi, R. N., Naleini, S. N., Ashtary-Larky, D., Peluso, I., Jouybari, L., Rafi, A., Ghorat, F., Heidari, N., Sharifian, F., Mardaneh, J., Aiello, P., Helbi, S., & Kooti, W. (2019). Anti-inflammatory and immunomodulatory effects of barberry (Berberis vulgaris) and its main compounds. Oxidative Medicine and Cellular Longevity, 2019, 1–10. https://doi.org/10.1155/2019/6183965
   Web of Science ®Google Scholar
• Keretsu, S., Bhujbal, S. P., & Cho, S. J. (2020). Rational approach toward COVID-19 main protease inhibitors via molecular docking, molecular dynamics simulation and free energy calculation. Scientific Reports, 10, 1–14. https://doi.org/10.1038/s41598-020-74468-0
   Google Scholar
• Kumar, V., Sari, A. N., Meidinna, H. N., Kaul, A., Basu, B., Ishida, Y., Terao, K., Kaul, S. C., Vrati, S., Sundar, D., & Wadhwa, R. (2023), Computational and experimental evidence of the anti-COVID-19 potential of honeybee propolis ingredients, caffeic acid phenethyl ester and artepillin c. Phytotherapy Research. https://doi.org/10.1002/ptr.7717
   Google Scholar
• Koes, D. R., Baumgartner, M. P., & Camacho, C. J. (2013). Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise. Journal of Chemical Information and Modeling, 53(8), 1893–1904. https://doi.org/10.1021/ci300604z
   PubMed Web of Science ®Google Scholar
• Kumari, R., Kumar, R., Open Source Drug Discovery Consortium, & Lynn, A. (2014). g_mmpbsa—A GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. https://doi.org/10.1021/ci500020m
   PubMed Web of Science ®Google Scholar
• Kupferschmidt, K., & Cohen, J. (2020). Will novel virus go pandemic or be contained?: American Association for the Advancement of Science. Science, 367(6478), 610–611. https://doi.org/10.1126/science.367.6478.610
   PubMed Web of Science ®Google Scholar
• Peñaloza, E. M. C., Costa, S. S., & Herrera-Calderon, O. (2023). Medicinal plants in peru as a source of immunomodulatory drugs potentially useful against COVID-19. Revista Brasileira de Farmacognosia, 33, 237–258. https://doi.org/10.1007/s43450-023-00367-w
   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(1), 387. https://doi.org/10.1038/s41392-022-01249-8
   PubMed Web of Science ®Google Scholar
• Li, P., Wang, Y., Lavrijsen, M., Lamers, M. M., DE Vries, A. C., Rottier, R. J., Bruno, M. J., Peppelenbosch, M. P., Haagmans, B. L., & Pan, Q. (2022). SARS-CoV-2 Omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination. Cell Research, 32(3), 322–324. https://doi.org/10.1038/s41422-022-00618-w
   PubMed Web of Science ®Google Scholar
• Liu, C., Zhou, Q., Li, Y., Garner, L. V., Watkins, S. P., Carter, L. J., Smoot, J., Gregg, A. C., Daniels, A. D., & Jervey, S. (2020). Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Publications.
   Google Scholar
• Liu, K., Watanabe, E., & Kokubo, H. (2017). Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations. Journal of Computer-Aided Molecular Design, 31(2), 201–211. https://doi.org/10.1007/s10822-016-0005-2
   PubMed Web of Science ®Google Scholar
• Love, O., Pacheco Lima, M. C., Clark, C., Cornillie, S., Roalstad, S., & Cheatham, T. (2022). Evaluating the accuracy of the AMBER protein force fields in modeling dihydrofolate reductase structures: Misbalance in the conformational arrangements of the flexible loop domains. Journal of Biomolecular Structure and Dynamics, 15, 1–15. https://doi.org/10.1080/07391102.2022.2098823.
   Google Scholar
• Ma, C., Sacco, M. D., Hurst, B., Townsend, J. A., Hu, Y., Szeto, T., Zhang, X., Tarbet, B., Marty, M. T., Chen, Y., & Wang, J. (2020). Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Research, 30(8), 678–692. https://doi.org/10.1038/s41422-020-0356-z
   PubMed Web of Science ®Google Scholar
• Magnavacca, A., Sangiovanni, E., Racagni, G., & Dell’agli, M. (2022). The antiviral and immunomodulatory activities of propolis: An update and future perspectives for respiratory diseases. Medicinal Research Reviews, 42(2), 897–945. https://doi.org/10.1002/med.21866
   PubMed Web of Science ®Google Scholar
• Matsuyama, S., Kawase, M., Nao, N., Shirato, K., Ujike, M., Kamitani, W., Shimojima, M., & Fukushi, S. J. B. (2020). The Inhaled Steroid Ciclesonide Blocks SARS-CoV-2 RNA Replication by Targeting the Viral Replication-Transcription Complex in Cultured Cells. Virology, 95(1), e01648–20. https://doi.org/10.1128/JVI.01648-20.
   Google Scholar
• Mazzafera, P., Crozier, A., & Magalhães, A. C. J. P. (1991). Caffeine metabolism in coffea arabica and other species of coffee. Phytochemistry, 30, 3913–3916.
   Google Scholar
• Mohapatra, P. K., Chopdar, K. S., Dash, G. C., Mohanty, A. K., & Raval, M. K. (2023). In silico screening and covalent binding of phytochemicals of Ocimum sanctum against SARS-CoV-2 (COVID 19) main protease. Journal of Biomolecular Structure & Dynamics, 41(2), 435–444. https://doi.org/10.1080/07391102.2021.2007170
   PubMed Web of Science ®Google Scholar
• Molinari, G. J. P. B. (2009). Natural products in drug discovery: Present status and perspectives. Advances in Experimental Medicine and Biology, 655, 13–27. https://doi.org/10.1007/978-1-4419-1132-2_2.
   Google Scholar
• Murakami, N., Hayden, R., Hills, T., Al-Samkari, H., Casey, J., Del Sorbo, L., Lawler, P. R., Sise, M. E., & Leaf, D. E. (2023). Therapeutic advances in COVID-19. Nature Reviews. Nephrology, 19(1), 38–52. https://doi.org/10.1038/s41581-022-00642-4
   PubMed Web of Science ®Google Scholar
• Nawrocki, G., Leontyev, I., Sakipov, S., Darkhovskiy, M., Kurnikov, I., Pereyaslavets, L., Kamath, G., Voronina, E., Butin, O., Illarionov, A., Olevanov, M., Kostikov, A., Ivahnenko, I., Patel, D. S., Sankaranarayanan, S. K. R. S, Kurnikova, M. G., Lock, C., Crooks G. E., Levitt, M., . . . Fain, B. (2022). Protein-Ligand Binding Free-Energy Calculations with ARROW–A Purely First-Principles Parameterized Polarizable Force Field. Journal of Chemical Theory and Computation, 18(12), 7751–7763. https://doi.org/10.1021/acs.jctc.2c00930.
   Google Scholar
• Park, A. Y. J., Tran, D. Q., Schaal, J. B., Wang, M., Selsted, M. E., & Beringer, P. M. (2022). Preclinical pharmacokinetics and safety of intravenous RTD-1. Antimicrobial Agents and Chemotherapy, 66(3), e0212521. https://doi.org/10.1128/aac.02125-21
   PubMed Web of Science ®Google Scholar
• Pathak, N., & Khandelwal, S. (2009). Immunomodulatory role of piperine in cadmium induced thymic atrophy and splenomegaly in mice. Environmental Toxicology and Pharmacology, 28(1), 52–60. https://doi.org/10.1016/j.etap.2009.02.003
   PubMed Web of Science ®Google Scholar
• Qiao, J., Li, Y.-S., Zeng, R., Liu, F.-L., Luo, R.-H., Huang, C., Wang, Y.-F., Zhang, J., Quan, B., Shen, C., Mao, X., Liu, X., Sun, W., Yang, W., Ni, X., Wang, K., Xu, L., Duan, Z.-L., Zou, Q.-C., … Yang, S. (2021). SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model. Science (New York, N.Y.), 371(6536), 1374–1378. https://doi.org/10.1126/science.abf1611
   PubMed Web of Science ®Google Scholar
• Shen, P., Jiao, Y., Miao, L., Chen, J. H., & Momtazi‐Borojeni, A. A. (2020). Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management. Journal of Cellular and Molecular Medicine, 24(21), 12234–12245. https://doi.org/10.1111/jcmm.15803
   PubMed Web of Science ®Google Scholar
• Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., Liu, W., Bi, Y., & Gao, G. F. (2016). Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends in Microbiology, 24(6), 490–502. https://doi.org/10.1016/j.tim.2016.03.003
   PubMed Web of Science ®Google Scholar
• Sunitha, K., & Nagulu, M. (2018). In vitro screening of immunomodulatory activity of methanolic leaves extract of Tecoma stans. International Research Journal of Pharmacy and Medical Sciences, 2, 52–54.
   Google Scholar
• Thawabteh, A., Juma, S., Bader, M., Karaman, D., Scrano, L., Bufo, S. A., & Karaman, R. J. T. (2019). The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens. Toxins, 11(11), 656. https://doi.org/10.3390/toxins11110656
   PubMed Web of Science ®Google Scholar
• Vanommeslaeghe, K., & MacKerell, A. D. (2012). Automation of the CHARMM General Force Field (CGenFF) I: Bond perception and atom typing. Journal of Chemical Information and Modeling, 52(12), 3144–3154. https://doi.org/10.1021/ci300363c
   PubMed Web of Science ®Google Scholar
• Wang, E., Sun, H., Wang, J., Wang, Z., Liu, H., Zhang, J. Z., & 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
• Watanabe, A., de Almeida, M. O., Deguchi, Y., Kozuka, R., Arruda, C., Berreta, A. A., Bastos, J. K., Woo, J.-T., & Yonezawa, T. (2021). Effects of baccharin isolated from Brazilian green propolis on adipocyte differentiation and hyperglycemia in ob/ob diabetic mice. International Journal of Molecular Sciences, 22(13), 6954. https://doi.org/10.3390/ijms22136954
   PubMed Web of Science ®Google Scholar
• Xia, Z., Sacco, M., Hu, Y., Ma, C., Meng, X., Zhang, F., Szeto, T., Xiang, Y., Chen, Y., & Wang, J. (2021). Rational design of hybrid SARS-CoV-2 main protease inhibitors guided by the superimposed cocrystal structures with the peptidomimetic inhibitors GC-376, telaprevir, and boceprevir. ACS Pharmacology & Translational Science, 4(4), 1408–1421. https://doi.org/10.1021/acsptsci.1c00099
   PubMedGoogle Scholar
• Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Niu, P., Liu, X., Zhao, L., Dong, E., Song, C., Zhan, S., Lu, R., Li, H., Tan, W., & Liu, D. (2020). In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases, 71(15), 732–739. https://doi.org/10.1093/cid/ciaa237
   PubMed Web of Science ®Google Scholar
• Zhang, C., Wu, Z., Li, J.-W., Zhao, H., & Wang, G.-Q. (2020a). Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. International Journal of Antimicrobial Agents, 55(5), 105954. https://doi.org/10.1016/j.ijantimicag.2020.105954
   PubMed Web of Science ®Google Scholar
• Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L., Becker, S., Rox, K., & Hilgenfeld, R. (2020b). Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science (New York, N.Y.), 368(6489), 409–412. https://doi.org/10.1126/science.abb3405
   PubMed Web of Science ®Google Scholar
• Zhou, S., Hill, C. S., Sarkar, S., Tse, L. V., Woodburn, B. M. D., Schinazi, R. F., Sheahan, T. P., Baric, R. S., Heise, M. T., & Swanstrom, R. (2021). β-d-N4-hydroxycytidine inhibits SARS-CoV-2 through lethal mutagenesis but is also mutagenic to mammalian cells. The Journal of Infectious Diseases, 224(3), 415–419. https://doi.org/10.1093/infdis/jiab247
   PubMed Web of Science ®Google Scholar