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image of Cyclin Dependent Kinases in Antiviral Drug Discovery

Abstract

Cyclin-dependent kinases that are responsible for cell cycle control, have been studied for over 30 years as therapeutic targets for the treatment of cancer and inflammation. In the past twenty years, their activities in various viral infections have been investigated in the search of novel therapeutic strategies in the treatment of viral infections. The interest in evaluating the antiviral activity of cyclin-dependent kinase inhibitors is closely linked to their role as host factors in viral replication. Due to the development of viral resistance, the strategies directed toward the targeting host machinery are still under investigation. This review is dedicated to the analysis of the molecular mechanisms of viral infection control by cyclin-dependent kinases that may reveal the potential mechanisms of action for their inhibitors and regulators as antiviral agents. We also consider recent efforts and achievements in the development of potential antiviral agents based on the cyclin-dependent kinase inhibitors and regulators, including their effects on various viruses, side effects, and toxicities.

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2025-03-31

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References

  1. Schirripa A. Sexl V. Kollmann K. Cyclin-dependent kinase inhibitors in malignant hematopoiesis. Front. Oncol. 2022 12 916682 10.3389/fonc.2022.916682 36033505
    [Google Scholar]
  2. Canavese M. Santo L. Raje N. Cyclin dependent kinases in cancer. Cancer Biol. Ther. 2012 13 7 451 457 10.4161/cbt.19589 22361734
    [Google Scholar]
  3. Ghafouri-Fard S. Khoshbakht T. Hussen B.M. Dong P. Gassler N. Taheri M. Baniahmad A. Dilmaghani N.A. A review on the role of cyclin dependent kinases in cancers. Cancer Cell Int. 2022 22 1 325 10.1186/s12935‑022‑02747‑z 36266723
    [Google Scholar]
  4. Zhang M. Zhang L. Hei R. Li X. Cai H. Wu X. Zheng Q. Cai C. CDK inhibitors in cancer therapy, an overview of recent development. Am. J. Cancer Res. 2021 11 5 1913 1935 34094661
    [Google Scholar]
  5. Boffo S. Damato A. Alfano L. Giordano A. CDK9 inhibitors in acute myeloid leukemia. J. Exp. Clin. Cancer Res. 2018 37 1 36 10.1186/s13046‑018‑0704‑8 29471852
    [Google Scholar]
  6. Luan Y. Li X. Luan Y. Luo J. Dong Q. Ye S. Li Y. Li Y. Jia L. Yang J. Yang D.H. Therapeutic challenges in peripheral T-cell lymphoma. Mol. Cancer 2024 23 1 2 10.1186/s12943‑023‑01904‑w 38178117
    [Google Scholar]
  7. Buisson R. Niraj J. Rodrigue A. Ho C.K. Kreuzer J. Foo T.K. Hardy E.J.L. Dellaire G. Haas W. Xia B. Masson J.Y. Zou L. Coupling of homologous recombination and the checkpoint by ATR. Mol. Cell 2017 65 2 336 346 10.1016/j.molcel.2016.12.007 28089683
    [Google Scholar]
  8. Juric V. Murphy B. Cyclin-dependent kinase inhibitors in brain cancer: Current state and future directions. Cancer Drug Resist. 2020 3 1 48 62 10.20517/cdr.2019.105 35582046
    [Google Scholar]
  9. Hajjo R. Sabbah D.A. Abusara O.H. Kharmah R. Bardaweel S. Targeting human proteins for antiviral drug discovery and repurposing efforts: A focus on protein kinases. Viruses 2023 15 2 568 10.3390/v15020568 36851782
    [Google Scholar]
  10. Yu Y. Deng Y.Q. Zou P. Wang Q. Dai Y. Yu F. Du L. Zhang N.N. Tian M. Hao J.N. Meng Y. Li Y. Zhou X. Fuk-Woo Chan J. Yuen K.Y. Qin C.F. Jiang S. Lu L. A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses. Nat. Commun. 2017 8 1 15672 10.1038/ncomms15672 28742068
    [Google Scholar]
  11. Wang L. Liang R. Gao Y. Li Y. Deng X. Xiang R. Zhang Y. Ying T. Jiang S. Yu F. Development of small-molecule inhibitors against Zika virus infection. Front. Microbiol. 2019 10 2725 10.3389/fmicb.2019.02725 31866959
    [Google Scholar]
  12. Zheng C. Tang Y.D. The emerging roles of the CDK/cyclin complexes in antiviral innate immunity. J. Med. Virol. 2022 94 6 2384 2387 10.1002/jmv.27554 34964486
    [Google Scholar]
  13. Yan Y. Tang Y. Zheng C. When cyclin-dependent kinases meet viral infections, including SARS-CoV-2. J. Med. Virol. 2022 94 7 2962 2968 10.1002/jmv.27719 35288942
    [Google Scholar]
  14. Rice A.P. Roles of CDKs in RNA polymerase II transcription of the HIV-1 genome. Transcription 2019 10 2 111 117 10.1080/21541264.2018.1542254 30375919
    [Google Scholar]
  15. Fan Y. Sanyal S. Bruzzone R. Breaking bad: How viruses subvert the cell cycle. Front. Cell. Infect. Microbiol. 2018 8 396 10.3389/fcimb.2018.00396 30510918
    [Google Scholar]
  16. Boeing S. Rigault C. Heidemann M. Eick D. Meisterernst M. RNA polymerase II C-terminal heptarepeat domain Ser-7 phosphorylation is established in a mediator-dependent fashion. J. Biol. Chem. 2010 285 1 188 196 10.1074/jbc.M109.046565 19901026
    [Google Scholar]
  17. Meinhart A. Cramer P. Recognition of RNA polymerase II carboxy-terminal domain by 3′-RNA-processing factors. Nature 2004 430 6996 223 226 10.1038/nature02679 15241417
    [Google Scholar]
  18. Wang S. Fischer P. Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology. Trends Pharmacol. Sci. 2008 29 6 302 313 10.1016/j.tips.2008.03.003 18423896
    [Google Scholar]
  19. Hong S. DNA damage response is hijacked by human papillomaviruses to complete their life cycle. J. Zhejiang Univ. Sci. B 2017 18 3 215 232 10.1631/jzus.B1600306 28271657
    [Google Scholar]
  20. Hartwell L.H. Culotti J. Reid B. Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc. Natl. Acad. Sci. USA 1970 66 2 352 359 10.1073/pnas.66.2.352 5271168
    [Google Scholar]
  21. Hartwell L.H. Mortimer R.K. Culotti J. Culotti M. Genetic control of the cell division cycle in yeast: V. genetic analysis of cdc mutants. Genetics 1973 74 2 267 286 10.1093/genetics/74.2.267 17248617
    [Google Scholar]
  22. Hartwell L.H. Culotti J. Pringle J.R. Reid B.J. Genetic control of the cell division cycle in yeast. Science 1974 183 4120 46 51 10.1126/science.183.4120.46 4587263
    [Google Scholar]
  23. Nurse P. Fission yeast cell cycle mutants and the logic of eukaryotic cell cycle control. Mol. Biol. Cell 2020 31 26 2871 2873 10.1091/mbc.E20‑10‑0623 33320707
    [Google Scholar]
  24. Liu J. Kipreos E.T. Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs): differential conservation of CAKs in yeast and metazoa. Mol. Biol. Evol. 2000 17 7 1061 1074 10.1093/oxfordjournals.molbev.a026387 10889219
    [Google Scholar]
  25. Malumbres M. Cyclin-dependent kinases. Genome Biol. 2014 15 6 122 10.1186/gb4184 25180339
    [Google Scholar]
  26. King R.W. Jackson P.K. Kirschner M.W. Mitosis in transition. Cell 1994 79 4 563 571 10.1016/0092‑8674(94)90542‑8 7954823
    [Google Scholar]
  27. Sherr C.J. G1 phase progression: Cycling on cue. Cell 1994 79 4 551 555 10.1016/0092‑8674(94)90540‑1 7954821
    [Google Scholar]
  28. Stillman B. Cell cycle control of DNA replication. Science 1996 274 5293 1659 1663 10.1126/science.274.5293.1659 8939847
    [Google Scholar]
  29. Hardcastle I.R. Golding B.T. Griffin R.J. Designing inhibitors of cyclin-dependent kinases. Annu. Rev. Pharmacol. Toxicol. 2002 42 1 325 348 10.1146/annurev.pharmtox.42.090601.125940 11807175
    [Google Scholar]
  30. Song X. Fang C. Dai Y. Sun Y. Qiu C. Lin X. Xu R. Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer. Br. J. Cancer 2024 130 8 1239 1248 10.1038/s41416‑024‑02589‑8 38355840
    [Google Scholar]
  31. Offermann A. Joerg V. Becker F. Roesch M.C. Kang D. Lemster A.L. Tharun L. Behrends J. Merseburger A.S. Culig Z. Sailer V. Brägelmann J. Kirfel J. Perner S. Inhibition of cyclin-dependent kinase 8/cyclin-dependent kinase 19 suppresses its pro-oncogenic effects in prostate cancer. Am. J. Pathol. 2022 192 5 813 823 10.1016/j.ajpath.2022.01.010 35181333
    [Google Scholar]
  32. Mounika P. Gurupadayya B. Kumar H.Y. Namitha B. An overview of CDK enzyme inhibitors in cancer therapy. Curr. Cancer Drug Targets 2023 23 8 603 619 10.2174/1568009623666230320144713 36959160
    [Google Scholar]
  33. Łukasik P. Załuski M. Gutowska I. Cyclin-Dependent Kinases (CDK) and their role in diseases development–review. Int. J. Mol. Sci. 2021 22 6 2935 10.3390/ijms22062935 33805800
    [Google Scholar]
  34. Quandt E. Ribeiro M.P.C. Clotet J. Atypical cyclins: the extended family portrait. Cell. Mol. Life Sci. 2020 77 2 231 242 10.1007/s00018‑019‑03262‑7 31420702
    [Google Scholar]
  35. Massacci G. Perfetto L. Sacco F. The Cyclin-dependent kinase 1: more than a cell cycle regulator. Br. J. Cancer 2023 129 11 1707 1716 10.1038/s41416‑023‑02468‑8 37898722
    [Google Scholar]
  36. Do P.A. Lee C.H. The role of CDK5 in tumours and tumour microenvironments. Cancers 2020 13 1 101 10.3390/cancers13010101 33396266
    [Google Scholar]
  37. Singh K. Cyclin dependent kinase as significant target for cancer treatment. CCTR 2012 8 3 225 235 10.2174/157339412802653164
    [Google Scholar]
  38. Wei P. Garber M.E. Fang S.M. Fischer W.H. Jones K.A. A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 1998 92 4 451 462 10.1016/S0092‑8674(00)80939‑3 9491887
    [Google Scholar]
  39. Yang X. Gold M.O. Tang D.N. Lewis D.E. Aguilar-Cordova E. Rice A.P. Herrmann C.H. TAK, an HIV Tat-associated kinase, is a member of the cyclin-dependent family of protein kinases and is induced by activation of peripheral blood lymphocytes and differentiation of promonocytic cell lines. Proc. Natl. Acad. Sci. USA 1997 94 23 12331 12336 10.1073/pnas.94.23.12331 9356449
    [Google Scholar]
  40. Mancebo H.S.Y. Lee G. Flygare J. Tomassini J. Luu P. Zhu Y. Peng J. Blau C. Hazuda D. Price D. Flores O. P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro. Genes Dev. 1997 11 20 2633 2644 10.1101/gad.11.20.2633 9334326
    [Google Scholar]
  41. Clark E. Santiago F. Deng L. Chong S. de la Fuente C. Wang L. Fu P. Stein D. Denny T. Lanka V. Mozafari F. Okamoto T. Kashanchi F. Loss of G(1)/S checkpoint in human immunodeficiency virus type 1-infected cells is associated with a lack of cyclin-dependent kinase inhibitor p21/Waf1. J. Virol. 2000 74 11 5040 5052 10.1128/JVI.74.11.5040‑5052.2000 10799578
    [Google Scholar]
  42. Pauls E. Ruiz A. Badia R. Permanyer M. Gubern A. Riveira-Muñoz E. Torres-Torronteras J. Álvarez M. Mothe B. Brander C. Crespo M. Menéndez-Arias L. Clotet B. Keppler O.T. Martí R. Posas F. Ballana E. Esté J.A. Cell cycle control and HIV-1 susceptibility are linked by CDK6-dependent CDK2 phosphorylation of SAMHD1 in myeloid and lymphoid cells. J. Immunol. 2014 193 4 1988 1997 10.4049/jimmunol.1400873 25015816
    [Google Scholar]
  43. Cribier A. Descours B. Valadão A.L.C. Laguette N. Benkirane M. Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction activity toward HIV-1. Cell Rep. 2013 3 4 1036 1043 10.1016/j.celrep.2013.03.017 23602554
    [Google Scholar]
  44. Ballana E. Esté J.A. SAMHD1: at the crossroads of cell proliferation, immune responses, and virus restriction. Trends Microbiol. 2015 23 11 680 692 10.1016/j.tim.2015.08.002 26439297
    [Google Scholar]
  45. Ruiz A. Pauls E. Badia R. Torres-Torronteras J. Riveira-Muñoz E. Clotet B. Martí R. Ballana E. Esté J.A. Cyclin D3-dependent control of the dNTP pool and HIV-1 replication in human macrophages. Cell Cycle 2015 14 11 1657 1665 10.1080/15384101.2015.1030558 25927932
    [Google Scholar]
  46. Martinat C. Cormier A. Tobaly-Tapiero J. Palmic N. Casartelli N. Mahboubi B. Coggins S.A.A. Buchrieser J. Persaud M. Diaz-Griffero F. Espert L. Bossis G. Lesage P. Schwartz O. Kim B. Margottin-Goguet F. Saïb A. Zamborlini A. SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells. Nat. Commun. 2021 12 1 4582 10.1038/s41467‑021‑24802‑5 34321470
    [Google Scholar]
  47. Guo S. Lei X. Chang Y. Zhao J. Wang J. Dong X. Liu Q. Zhang Z. Wang L. Yi D. Ma L. Li Q. Zhang Y. Ding J. Liang C. Li X. Guo F. Wang J. Cen S. SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis. Signal Transduct. Target. Ther. 2022 7 1 400 10.1038/s41392‑022‑01239‑w 36575184
    [Google Scholar]
  48. Izumiya Y. Lin S.F. Ellison T.J. Levy A.M. Mayeur G.L. Izumiya C. Kung H.J. Cell cycle regulation by Kaposi’s sarcoma-associated herpesvirus K-bZIP: direct interaction with cyclin-CDK2 and induction of G1 growth arrest. J. Virol. 2003 77 17 9652 9661 10.1128/JVI.77.17.9652‑9661.2003 12915577
    [Google Scholar]
  49. Saxena N. Kumar V. The HBx oncoprotein of hepatitis B virus deregulates the cell cycle by promoting the intracellular accumulation and re-compartmentalization of the cellular deubiquitinase USP37. PLoS One 2014 9 10 e111256 10.1371/journal.pone.0111256 25347529
    [Google Scholar]
  50. Sato Y. Watanabe T. Suzuki C. Abe Y. Masud H.M.A.A. Inagaki T. Yoshida M. Suzuki T. Goshima F. Adachi J. Tomonaga T. Murata T. Kimura H. S-like-phase cyclin-dependent kinases stabilize the Epstein-Barr Virus BDLF4 protein to temporally control late gene transcription. J. Virol. 2019 93 8 e01707-18 10.1128/JVI.01707‑18 30700607
    [Google Scholar]
  51. Schütz M. Cordsmeier A. Wangen C. Horn A.H.C. Wyler E. Ensser A. Sticht H. Marschall M. The interactive complex between cytomegalovirus kinase vCDK/pUL97 and host factors CDK7–Cyclin H determines individual patterns of transcription in infected cells. Int. J. Mol. Sci. 2023 24 24 17421 10.3390/ijms242417421 38139252
    [Google Scholar]
  52. Spaziani A. Alisi A. Sanna D. Balsano C. Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1. J. Biol. Chem. 2006 281 16 10983 10989 10.1074/jbc.M512536200 16446363
    [Google Scholar]
  53. Gutierrez-Chamorro L. Felip E. Ezeonwumelu I.J. Margelí M. Ballana E. Cyclin-dependent kinases as emerging targets for developing novel antiviral therapeutics. Trends Microbiol. 2021 29 9 836 848 10.1016/j.tim.2021.01.014 33618979
    [Google Scholar]
  54. Li Y. Zhang J. Gao W. Zhang L. Pan Y. Zhang S. Wang Y. Insights on structural characteristics and ligand binding mechanisms of CDK2. Int. J. Mol. Sci. 2015 16 5 9314 9340 10.3390/ijms16059314 25918937
    [Google Scholar]
  55. Peyressatre M. Prével C. Pellerano M. Morris M. Targeting cyclin-dependent kinases in human cancers: from small molecules to Peptide inhibitors. Cancers (Basel) 2015 7 1 179 237 10.3390/cancers7010179 25625291
    [Google Scholar]
  56. Knight J.D.R. Qian B. Baker D. Kothary R. Conservation, variability and the modeling of active protein kinases. PLoS One 2007 2 10 e982 10.1371/journal.pone.0000982 17912359
    [Google Scholar]
  57. Guendel I. Agbottah E.T. Kehn-Hall K. Kashanchi F. Inhibition of human immunodeficiency virus type-1 by cdk inhibitors. AIDS Res. Ther. 2010 7 1 7 10.1186/1742‑6405‑7‑7 20334651
    [Google Scholar]
  58. Sedlacek H. Czech J. Naik R. Kaur G. Worland P. Losiewicz M. Parker B. Carlson B. Smith A. Senderowicz A. Sausville E. Flavopiridol (L86 8275; NSC 649890), a new kinase inhibitor for tumor therapy. Int. J. Oncol. 1996 9 6 1143 1168 10.3892/ijo.9.6.1143 21541623
    [Google Scholar]
  59. Julve M. Clark J.J. Lythgoe M.P. Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma. Expert Opin. Pharmacother. 2021 22 3 351 361 10.1080/14656566.2020.1828348 33030382
    [Google Scholar]
  60. Perwitasari O. Yan X. O’Donnell J. Johnson S. Tripp R.A. Repurposing kinase inhibitors as antiviral agents to control Influenza A virus replication. Assay Drug Dev. Technol. 2015 13 10 638 649 10.1089/adt.2015.0003.drrr 26192013
    [Google Scholar]
  61. Badshah S.L. Faisal S. Muhammad A. Poulson B.G. Emwas A.H. Jaremko M. Antiviral activities of flavonoids. Biomed. Pharmacother. 2021 140 111596 10.1016/j.biopha.2021.111596 34126315
    [Google Scholar]
  62. Chao S.H. Fujinaga K. Marion J.E. Taube R. Sausville E.A. Senderowicz A.M. Peterlin B.M. Price D.H. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. J. Biol. Chem. 2000 275 37 28345 28348 10.1074/jbc.C000446200 10906320
    [Google Scholar]
  63. Schang L.M. Discovery of the antiviral activities of pharmacologic cyclin-dependent kinase inhibitors: from basic to applied science. Expert Rev. Anti Infect. Ther. 2005 3 2 145 149 10.1586/14787210.3.2.145 15918771
    [Google Scholar]
  64. Holcakova J. Tomasec P. Bugert J.J. Wang E.C.Y. Wilkinson G.W.G. Hrstka R. Krystof V. Strnad M. Vojtesek B. The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties. Antivir. Chem. Chemother. 2010 20 3 133 142 10.3851/IMP1460 20054100
    [Google Scholar]
  65. Baker A. Gregory G.P. Verbrugge I. Kats L. Hilton J.J. Vidacs E. Lee E.M. Lock R.B. Zuber J. Shortt J. Johnstone R.W. The CDK9 inhibitor dinaciclib exerts potent apoptotic and antitumor effects in preclinical models of MLL-rearranged acute myeloid leukemia. Cancer Res. 2016 76 5 1158 1169 10.1158/0008‑5472.CAN‑15‑1070 26627013
    [Google Scholar]
  66. Johnson A.J. Yeh Y-Y. Smith L.L. Wagner A.J. Hessler J. Gupta S. Flynn J. Jones J. Zhang X. Bannerji R. Grever M.R. Byrd J.C. The novel cyclin-dependent kinase inhibitor dinaciclib (SCH727965) promotes apoptosis and abrogates microenvironmental cytokine protection in chronic lymphocytic leukemia cells. Leukemia 2012 26 12 2554 2557 10.1038/leu.2012.144 22791353
    [Google Scholar]
  67. Hossain D.M.S. Javaid S. Cai M. Zhang C. Sawant A. Hinton M. Sathe M. Grein J. Blumenschein W. Pinheiro E.M. Chackerian A. Dinaciclib induces immunogenic cell death and enhances anti-PD1–mediated tumor suppression. J. Clin. Invest. 2018 128 2 644 654 10.1172/JCI94586 29337311
    [Google Scholar]
  68. Bouhaddou M. Memon D. Meyer B. White K.M. Rezelj V.V. Correa Marrero M. Polacco B.J. Melnyk J.E. Ulferts S. Kaake R.M. Batra J. Richards A.L. Stevenson E. Gordon D.E. Rojc A. Obernier K. Fabius J.M. Soucheray M. Miorin L. Moreno E. Koh C. Tran Q.D. Hardy A. Robinot R. Vallet T. Nilsson-Payant B.E. Hernandez-Armenta C. Dunham A. Weigang S. Knerr J. Modak M. Quintero D. Zhou Y. Dugourd A. Valdeolivas A. Patil T. Li Q. Hüttenhain R. Cakir M. Muralidharan M. Kim M. Jang G. Tutuncuoglu B. Hiatt J. Guo J.Z. Xu J. Bouhaddou S. Mathy C.J.P. Gaulton A. Manners E.J. Félix E. Shi Y. Goff M. Lim J.K. McBride T. O’Neal M.C. Cai Y. Chang J.C.J. Broadhurst D.J. Klippsten S. De wit E. Leach A.R. Kortemme T. Shoichet B. Ott M. Saez-Rodriguez J. tenOever B.R. Mullins R.D. Fischer E.R. Kochs G. Grosse R. García-Sastre A. Vignuzzi M. Johnson J.R. Shokat K.M. Swaney D.L. Beltrao P. Krogan N.J. The global phosphorylation landscape of SARS-CoV-2 infection. Cell 2020 182 3 685 712.e19 10.1016/j.cell.2020.06.034 32645325
    [Google Scholar]
  69. Gargouri M. Alzwi A. Abobaker A. Cyclin dependent kinase inhibitors as a new potential therapeutic option in management of COVID-19. Med. Hypotheses 2021 146 110380 10.1016/j.mehy.2020.110380 33213999
    [Google Scholar]
  70. Shirsath N.P. Manohar S.M. Joshi K.S. P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines. Mol. Cancer 2012 11 1 77 10.1186/1476‑4598‑11‑77 23075291
    [Google Scholar]
  71. De Azevedo W.F. Jr Mueller-Dieckmann H.J. Schulze-Gahmen U. Worland P.J. Sausville E. Kim S.H. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc. Natl. Acad. Sci. USA 1996 93 7 2735 2740 10.1073/pnas.93.7.2735 8610110
    [Google Scholar]
  72. Alessandri A.L. Duffin R. Leitch A.E. Lucas C.D. Sheldrake T.A. Dorward D.A. Hirani N. Pinho V. de Sousa L.P. Teixeira M.M. Lyons J.F. Haslett C. Rossi A.G. Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One 2011 6 9 e25683 10.1371/journal.pone.0025683 21984938
    [Google Scholar]
  73. Rigas A.C. Robson C.N. Curtin N.J. Therapeutic potential of CDK inhibitor NU2058 in androgen-independent prostate cancer. Oncogene 2007 26 55 7611 7619 10.1038/sj.onc.1210586 17599054
    [Google Scholar]
  74. Ali A. Ghosh A. Nathans R.S. Sharova N. O’Brien S. Cao H. Stevenson M. Rana T.M. Identification of flavopiridol analogues that selectively inhibit positive transcription elongation factor (P-TEFb) and block HIV-1 replication. ChemBioChem 2009 10 12 2072 2080 10.1002/cbic.200900303 19603446
    [Google Scholar]
  75. Zhang Y. Guo J. Liu Y. Qu Y. Li Y.Q. Mu Y. Li W. An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase. Int. J. Biol. Macromol. 2024 265 Pt 1 130644 10.1016/j.ijbiomac.2024.130644 38462102
    [Google Scholar]
  76. Sarkar A. Mandal K. Repurposing an antiviral drug against SARS-CoV-2 main protease. Angew. Chem. Int. Ed. 2021 60 44 23492 23494 10.1002/anie.202107481 34545983
    [Google Scholar]
  77. Bogdanow B. Schmidt M. Weisbach H. Gruska I. Vetter B. Imami K. Ostermann E. Brune W. Selbach M. Hagemeier C. Wiebusch L. Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis. Nat. Commun. 2020 11 1 4845 10.1038/s41467‑020‑18542‑1 32973148
    [Google Scholar]
  78. Filgueira de Azevedo W. Jr Canduri F. Freitas da Silveira N.J. Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol. Biochem. Biophys. Res. Commun. 2002 293 1 566 571 10.1016/S0006‑291X(02)00266‑8 12054639
    [Google Scholar]
  79. Shah M. Nunes M.R. Stearns V. CDK4/6 inhibitors: Game changers in the management of hormone receptor–positive advanced breast cancer? Oncology (Williston Park) 2018 32 5 216 222 29847850
    [Google Scholar]
  80. Xu J. Xue Y. Zhou R. Shi P.Y. Li H. Zhou J. Drug repurposing approach to combating coronavirus: Potential drugs and drug targets. Med. Res. Rev. 2021 41 3 1375 1426 10.1002/med.21763 33277927
    [Google Scholar]
  81. Jeon S. Ko M. Lee J. Choi I. Byun S.Y. Park S. Shum D. Kim S. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. Antimicrob. Agents Chemother. 2020 64 7 e00819-20 10.1128/AAC.00819‑20 32366720
    [Google Scholar]
  82. Castellví M. Felip E. Ezeonwumelu I. Badia R. Garcia-Vidal E. Pujantell M. Gutiérrez-Chamorro L. Teruel I. Martínez-Cardús A. Clotet B. Riveira-Muñoz E. Margelí M. Esté J. Ballana E. Pharmacological modulation of SAMHD1 activity by CDK4/6 inhibitors improves anticancer therapy. Cancers (Basel) 2020 12 3 713 10.3390/cancers12030713 32197329
    [Google Scholar]
  83. Schor S. Einav S. Repurposing of kinase inhibitors as broad-spectrum antiviral drugs. DNA Cell Biol. 2018 37 2 63 69 10.1089/dna.2017.4033 29148875
    [Google Scholar]
  84. Pauls E. Badia R. Torres-Torronteras J. Ruiz A. Permanyer M. Riveira-Muñoz E. Clotet B. Marti R. Ballana E. Esté J.A. Palbociclib, a selective inhibitor of cyclin-dependent kinase4/6, blocks HIV-1 reverse transcription through the control of sterile α motif and HD domain-containing protein-1 (SAMHD1) activity. AIDS 2014 28 15 2213 2222 10.1097/QAD.0000000000000399 25036183
    [Google Scholar]
  85. Xue Y. Mei H. Chen Y. Griffin J.D. Liu Q. Weisberg E. Yang J. Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS-CoV-2. MedComm 2023 4 3 e254 10.1002/mco2.254 37193304
    [Google Scholar]
  86. Bahadur Gurung A. Ajmal Ali M. Elshikh M.S. Aref I. Amina M. Lee J. An in silico approach unveils the potential of antiviral compounds in preclinical and clinical trials as SARS-CoV-2 omicron inhibitors. Saudi J. Biol. Sci. 2022 29 6 103297 10.1016/j.sjbs.2022.103297 35475118
    [Google Scholar]
  87. Wang S. Sun Q. Xu Y. Pei J. Lai L. A transferable deep learning approach to fast screen potent antiviral drugs against SARS-CoV-2. bioRxiv 2020 2020 271569 10.1101/2020.08.28.271569
    [Google Scholar]
  88. Syrigos G.V. Feige M. Dirlam A. Businger R. Gruska I. Wiebusch L. Hamprecht K. Schindler M. Abemaciclib restricts HCMV replication by suppressing pUL97-mediated phosphorylation of SAMHD1. Antiviral Res. 2023 217 105689 10.1016/j.antiviral.2023.105689 37516154
    [Google Scholar]
  89. Wild M. Kicuntod J. Seyler L. Wangen C. Bertzbach L.D. Conradie A.M. Kaufer B.B. Wagner S. Michel D. Eickhoff J. Tsogoeva S.B. Bäuerle T. Hahn F. Marschall M. Combinatorial drug treatments reveal promising anticytomegaloviral profiles for clinically relevant Pharmaceutical Kinase Inhibitors (PKIs). Int. J. Mol. Sci. 2021 22 2 575 10.3390/ijms22020575 33430060
    [Google Scholar]
  90. Jiang L. Yu Y. Li Z. Gao Y. Zhang H. Zhang M. Cao W. Peng Q. Chen X. BMS-265246, a cyclin-dependent kinase inhibitor, inhibits the infection of Herpes Simplex Virus Type 1. Viruses 2023 15 8 1642 10.3390/v15081642 37631985
    [Google Scholar]
  91. Fang G. Chen H. Cheng Z. Tang Z. Wan Y. Azaindole derivatives as potential kinase inhibitors and their SARs elucidation. Eur. J. Med. Chem. 2023 258 115621 10.1016/j.ejmech.2023.115621 37423125
    [Google Scholar]
  92. Zhao L. Yan Y. Dai Q. Wang Z. Yin J. Xu Y. Wang Z. Guo X. Li W. Cao R. Zhong W. The CDK1 inhibitor, Ro-3306, is a potential antiviral candidate against influenza virus infection. Antiviral Res. 2022 201 105296 10.1016/j.antiviral.2022.105296 35367281
    [Google Scholar]
  93. Singh R. Bhardwaj V. Das P. Purohit R. Natural analogues inhibiting selective cyclin-dependent kinase protein isoforms: a computational perspective. J. Biomol. Struct. Dyn. 2020 38 17 5126 5135 10.1080/07391102.2019.1696709 31760872
    [Google Scholar]
  94. Yu D. Wagner S. Schütz M. Jeon Y. Seo M. Kim J. Brückner N. Kicuntod J. Tillmanns J. Wangen C. Hahn F. Kaufer B.B. Neipel F. Eickhoff J. Klebl B. Nam K. Marschall M. An antiherpesviral host-directed strategy based on CDK7 covalently binding drugs: Target-selective, picomolar-dose, cross-virus reactivity. Pharmaceutics 2024 16 2 158 10.3390/pharmaceutics16020158 38399219
    [Google Scholar]
  95. Hutterer C. Eickhoff J. Milbradt J. Korn K. Zeitträger I. Bahsi H. Wagner S. Zischinsky G. Wolf A. Degenhart C. Unger A. Baumann M. Klebl B. Marschall M. A novel CDK7 inhibitor of the Pyrazolotriazine class exerts broad-spectrum antiviral activity at nanomolar concentrations. Antimicrob. Agents Chemother. 2015 59 4 2062 2071 10.1128/AAC.04534‑14 25624324
    [Google Scholar]
  96. Yamamoto M. Onogi H. Kii I. Yoshida S. Iida K. Sakai H. Abe M. Tsubota T. Ito N. Hosoya T. Hagiwara M. CDK9 inhibitor FIT-039 prevents replication of multiple DNA viruses. J. Clin. Invest. 2014 124 8 3479 3488 10.1172/JCI73805 25003190
    [Google Scholar]
  97. Tanaka T. Okuyama-Dobashi K. Murakami S. Chen W. Okamoto T. Ueda K. Hosoya T. Matsuura Y. Ryo A. Tanaka Y. Hagiwara M. Moriishi K. Inhibitory effect of CDK9 inhibitor FIT-039 on hepatitis B virus propagation. Antiviral Res. 2016 133 156 164 10.1016/j.antiviral.2016.08.008 27515132
    [Google Scholar]
  98. Porter D.C. Farmaki E. Altilia S. Schools G.P. West D.K. Chen M. Chang B.D. Puzyrev A.T. Lim C. Rokow-Kittell R. Friedhoff L.T. Papavassiliou A.G. Kalurupalle S. Hurteau G. Shi J. Baran P.S. Gyorffy B. Wentland M.P. Broude E.V. Kiaris H. Roninson I.B. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc. Natl. Acad. Sci. USA 2012 109 34 13799 13804 10.1073/pnas.1206906109 22869755
    [Google Scholar]
  99. Kokinos E.K. Tsymbal S.A. Galochkina A.V. Bezlepkina S.A. Nikolaeva J.V. Vershinina S.O. Shtro A.A. Tatarskiy V.V. Shtil A.A. Broude E.V. Roninson I.B. Dukhinova M. Inhibition of cyclin-dependent kinases 8/19 restricts bacterial and virus-induced inflammatory responses in monocytes. Viruses 2023 15 6 1292 10.3390/v15061292 37376593
    [Google Scholar]
  100. Horvath R.M. Brumme Z.L. Sadowski I. Small molecule inhibitors of transcriptional cyclin-dependent kinases impose HIV-1 latency, presenting “block and lock” treatment strategies. Antimicrob. Agents Chemother. 2024 68 3 e01072-23 10.1128/aac.01072‑23 38319085
    [Google Scholar]
  101. Ivanov S. Lagunin A. Filimonov D. Tarasova O. Network-based analysis of OMICs data to understand the HIV–host interaction. Front. Microbiol. 2020 11 1314 10.3389/fmicb.2020.01314 32625189
    [Google Scholar]
  102. Vansant G. Bruggemans A. Janssens J. Debyser Z. Block-and-lock strategies to cure HIV infection. Viruses 2020 12 1 84 10.3390/v12010084 31936859
    [Google Scholar]
  103. Olson C.M. Liang Y. Leggett A. Park W.D. Li L. Mills C.E. Elsarrag S.Z. Ficarro S.B. Zhang T. Düster R. Geyer M. Sim T. Marto J.A. Sorger P.K. Westover K.D. Lin C.Y. Kwiatkowski N. Gray N.S. Development of a selective CDK7 covalent inhibitor reveals predominant cell-cycle phenotype. Cell Chem. Biol. 2019 26 6 792 803.e10 10.1016/j.chembiol.2019.02.012 30905681
    [Google Scholar]
  104. Albert T.K. Rigault C. Eickhoff J. Baumgart K. Antrecht C. Klebl B. Mittler G. Meisterernst M. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br. J. Pharmacol. 2014 171 1 55 68 10.1111/bph.12408 24102143
    [Google Scholar]
  105. Clopper K.C. Taatjes D.J. Chemical inhibitors of transcription-associated kinases. Curr. Opin. Chem. Biol. 2022 70 102186 10.1016/j.cbpa.2022.102186 35926294
    [Google Scholar]
  106. Bhurta D. Bharate S.B. Analyzing the scaffold diversity of cyclin-dependent kinase inhibitors and revisiting the clinical and preclinical pipeline. Med. Res. Rev. 2022 42 2 654 709 10.1002/med.21856 34605036
    [Google Scholar]
  107. Yadav R. Chaudhary J.K. Jain N. Chaudhary P.K. Khanra S. Dhamija P. Sharma A. Kumar A. Handu S. Role of structural and non-structural proteins and therapeutic targets of SARS-CoV-2 for COVID-19. Cells 2021 10 4 821 10.3390/cells10040821 33917481
    [Google Scholar]
  108. Valle M. Structural homology between nucleoproteins of ssRNA viruses. Subcell. Biochem. 2018 88 129 145 10.1007/978‑981‑10‑8456‑0_6 29900495
    [Google Scholar]
  109. Saito A. Shofa M. Ode H. Yumiya M. Hirano J. Okamoto T. Yoshimura S.H. How do flaviviruses hijack host cell functions by phase separation? Viruses 2021 13 8 1479 10.3390/v13081479 34452345
    [Google Scholar]
  110. Tavakolian S. Goudarzi H. Faghihloo E. Cyclin-dependent kinases and CDK inhibitors in virus-associated cancers. Infect. Agent. Cancer 2020 15 1 27 10.1186/s13027‑020‑00295‑7 32377232
    [Google Scholar]
  111. He W. Staples D. Smith C. Fisher C. Direct activation of cyclin-dependent kinase 2 by human papillomavirus E7. J. Virol. 2003 77 19 10566 10574 10.1128/JVI.77.19.10566‑10574.2003 12970441
    [Google Scholar]
  112. Pal A. Kundu R. Human papillomavirus E6 and E7: The cervical cancer hallmarks and targets for therapy. Front. Microbiol. 2020 10 3116 10.3389/fmicb.2019.03116 32038557
    [Google Scholar]
  113. Tomaić V. Functional roles of E6 and E7 oncoproteins in HPV-induced malignancies at diverse anatomical sites. Cancers 2016 8 10 95 10.3390/cancers8100095 27775564
    [Google Scholar]
  114. Vats A. Trejo-Cerro O. Thomas M. Banks L. Human papillomavirus E6 and E7: What remains? Tumour Virus Research 2021 11 200213 10.1016/j.tvr.2021.200213 33716206
    [Google Scholar]
  115. Kim J.E.E.E.U.N. Lee J.I.I.N. Jin D.H. Lee W.J. Park G.B. Kim S. Kim Y.S. Wu T.C. Hur D.Y. Kim D. Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2. Oncol. Rep. 2014 31 5 2429 2437 10.3892/or.2014.3082 24627094
    [Google Scholar]
  116. Kumar P. Murakami M. Kaul R. Saha A. Cai Q. Robertson E.S. Deregulation of the cell cycle machinery by Epstein-Barr virus nuclear antigen 3C. Future Virol. 2009 4 1 79 91 10.2217/17460794.4.1.79 25635182
    [Google Scholar]
  117. Cereseto A. Parks R.W. Rivadeneira E. Franchini G. Limiting amounts of p27Kip1 correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells. Oncogene 1999 18 15 2441 2450 10.1038/sj.onc.1202567 10229195
    [Google Scholar]
  118. Baydoun H.H. Pancewicz J. Bai X. Nicot C. HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression. Mol. Cancer 2010 9 1 302 10.1186/1476‑4598‑9‑302 21092281
    [Google Scholar]
  119. Grassmann R. Aboud M. Jeang K.T. Molecular mechanisms of cellular transformation by HTLV-1 Tax. Oncogene 2005 24 39 5976 5985 10.1038/sj.onc.1208978 16155604
    [Google Scholar]
  120. Yen A. Sturgill R. Varvayanis S. Chern R. FMS (CSF-1 receptor) prolongs cell cycle and promotes retinoic acid-induced hypophosphorylation of retinoblastoma protein, G1 arrest, and cell differentiation. Exp. Cell Res. 1996 229 1 111 125 10.1006/excr.1996.0349 8940255
    [Google Scholar]
  121. Bouchard M. Giannakopoulos S. Wang E.H. Tanese N. Schneider R.J. Hepatitis B. Hepatitis B virus HBx protein activation of cyclin A-cyclin-dependent kinase 2 complexes and G1 transit via a Src kinase pathway. J. Virol. 2001 75 9 4247 4257 10.1128/JVI.75.9.4247‑4257.2001 11287574
    [Google Scholar]
  122. Bahnassy A.A. Zekri A.R.N. Loutfy S.A. Mohamed W.S. Moneim A.A. Salem S.E. Sheta M.M. Omar A. Al-Zawahry H. The role of cyclins and cyclin dependent kinases in development and progression of hepatitis C virus-genotype 4-associated hepatitis and hepatocellular carcinoma. Exp. Mol. Pathol. 2011 91 2 643 652 10.1016/j.yexmp.2011.06.014 21801719
    [Google Scholar]
  123. Tarasova O. Poroikov V. Machine learning in discovery of new antivirals and optimization of viral infections therapy. Curr. Med. Chem. 2021 28 38 7840 7861 10.2174/0929867328666210504114351 33949929
    [Google Scholar]
  124. Wild M. Hahn F. Brückner N. Schütz M. Wangen C. Wagner S. Sommerer M. Strobl S. Marschall M. Cyclin-Dependent Kinases (CDKs) and the human cytomegalovirus-encoded CDK ortholog pUL97 represent highly attractive targets for synergistic drug combinations. Int. J. Mol. Sci. 2022 23 5 2493 10.3390/ijms23052493 35269635
    [Google Scholar]
  125. Jhaveri K. Burris H.A. III Yap T.A. Hamilton E. Rugo H.S. Goldman J.W. Dann S. Liu F. Wong G.Y. Krupka H. Shapiro G.I. The evolution of cyclin dependent kinase inhibitors in the treatment of cancer. Expert Rev. Anticancer Ther. 2021 21 10 1105 1124 10.1080/14737140.2021.1944109 34176404
    [Google Scholar]
  126. Onesti C.E. Jerusalem G. CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. A systematic review and meta-analysis. Expert Rev. Anticancer Ther. 2021 21 3 283 298 10.1080/14737140.2021.1852934 33233970
    [Google Scholar]
  127. Ballana E. Badia R. Terradas G. Torres-Torronteras J. Ruiz A. Pauls E. Riveira-Muñoz E. Clotet B. Martí R. Esté J.A. SAMHD1 specifically affects the antiviral potency of thymidine analog HIV reverse transcriptase inhibitors. Antimicrob. Agents Chemother. 2014 58 8 4804 4813 10.1128/AAC.03145‑14 24913159
    [Google Scholar]
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Cyclin Dependent Kinases in Antiviral Drug Discovery
Bentham Science Publishers ; https://doi.org/10.2174/0109298673334631241208131015
/content/journals/cmc/10.2174/0109298673334631241208131015
/content/journals/cmc/10.2174/0109298673334631241208131015
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  • Article Type:     Review Article
Keywords: Cyclin-dependent kinase ; viral infections ; transcriptional regulation ; antiviral drugs ; inhibitors ; pharmacological agents ; anti-inflammatory drugs

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