Skip to content
2000
Volume 32, Issue 34
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

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 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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673334631241208131015
2025-02-10
2025-11-01

  • From This Site

    /content/journals/cmc/10.2174/0109298673334631241208131015
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SchirripaA. SexlV. KollmannK. Cyclin-dependent kinase inhibitors in malignant hematopoiesis.Front. Oncol.20221291668210.3389/fonc.2022.91668236033505
     [Google Scholar]
  2. CanaveseM. SantoL. RajeN. Cyclin dependent kinases in cancer.Cancer Biol. Ther.201213745145710.4161/cbt.1958922361734
     [Google Scholar]
  3. Ghafouri-FardS. KhoshbakhtT. HussenB.M. DongP. GasslerN. TaheriM. BaniahmadA. DilmaghaniN.A. A review on the role of cyclin dependent kinases in cancers.Cancer Cell Int.202222132510.1186/s12935‑022‑02747‑z36266723
     [Google Scholar]
  4. ZhangM. ZhangL. HeiR. LiX. CaiH. WuX. ZhengQ. CaiC. CDK inhibitors in cancer therapy, an overview of recent development.Am. J. Cancer Res.20211151913193534094661
     [Google Scholar]
  5. BoffoS. DamatoA. AlfanoL. GiordanoA. CDK9 inhibitors in acute myeloid leukemia.J. Exp. Clin. Cancer Res.20183713610.1186/s13046‑018‑0704‑829471852
     [Google Scholar]
  6. LuanY. LiX. LuanY. LuoJ. DongQ. YeS. LiY. LiY. JiaL. YangJ. YangD.H. Therapeutic challenges in peripheral T-cell lymphoma.Mol. Cancer2024231210.1186/s12943‑023‑01904‑w38178117
     [Google Scholar]
  7. BuissonR. NirajJ. RodrigueA. HoC.K. KreuzerJ. FooT.K. HardyE.J.L. DellaireG. HaasW. XiaB. MassonJ.Y. ZouL. Coupling of homologous recombination and the checkpoint by ATR.Mol. Cell201765233634610.1016/j.molcel.2016.12.00728089683
     [Google Scholar]
  8. JuricV. MurphyB. Cyclin-dependent kinase inhibitors in brain cancer: Current state and future directions.Cancer Drug Resist.202031486210.20517/cdr.2019.10535582046
     [Google Scholar]
  9. HajjoR. SabbahD.A. AbusaraO.H. KharmahR. BardaweelS. Targeting human proteins for antiviral drug discovery and repurposing efforts: A focus on protein kinases.Viruses202315256810.3390/v1502056836851782
     [Google Scholar]
  10. YuY. DengY.Q. ZouP. WangQ. DaiY. YuF. DuL. ZhangN.N. TianM. HaoJ.N. MengY. LiY. ZhouX. Fuk-Woo ChanJ. YuenK.Y. QinC.F. JiangS. LuL. A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses.Nat. Commun.2017811567210.1038/ncomms1567228742068
     [Google Scholar]
  11. WangL. LiangR. GaoY. LiY. DengX. XiangR. ZhangY. YingT. JiangS. YuF. Development of small-molecule inhibitors against Zika virus infection.Front. Microbiol.201910272510.3389/fmicb.2019.0272531866959
     [Google Scholar]
  12. ZhengC. TangY.D. The emerging roles of the CDK/cyclin complexes in antiviral innate immunity.J. Med. Virol.20229462384238710.1002/jmv.2755434964486
     [Google Scholar]
  13. YanY. TangY. ZhengC. When cyclin-dependent kinases meet viral infections, including SARS-CoV-2.J. Med. Virol.20229472962296810.1002/jmv.2771935288942
     [Google Scholar]
  14. RiceA.P. Roles of CDKs in RNA polymerase II transcription of the HIV-1 genome.Transcription201910211111710.1080/21541264.2018.154225430375919
     [Google Scholar]
  15. FanY. SanyalS. BruzzoneR. Breaking bad: How viruses subvert the cell cycle.Front. Cell. Infect. Microbiol.2018839610.3389/fcimb.2018.0039630510918
     [Google Scholar]
  16. BoeingS. RigaultC. HeidemannM. EickD. MeisterernstM. RNA polymerase II C-terminal heptarepeat domain Ser-7 phosphorylation is established in a mediator-dependent fashion.J. Biol. Chem.2010285118819610.1074/jbc.M109.04656519901026
     [Google Scholar]
  17. MeinhartA. CramerP. Recognition of RNA polymerase II carboxy-terminal domain by 3′-RNA-processing factors.Nature2004430699622322610.1038/nature0267915241417
     [Google Scholar]
  18. WangS. FischerP. Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology.Trends Pharmacol. Sci.200829630231310.1016/j.tips.2008.03.00318423896
     [Google Scholar]
  19. HongS. DNA damage response is hijacked by human papillomaviruses to complete their life cycle.J. Zhejiang Univ. Sci. B201718321523210.1631/jzus.B160030628271657
     [Google Scholar]
  20. HartwellL.H. CulottiJ. ReidB. Genetic control of the cell-division cycle in yeast. I. Detection of mutants.Proc. Natl. Acad. Sci. USA197066235235910.1073/pnas.66.2.3525271168
     [Google Scholar]
  21. HartwellL.H. MortimerR.K. CulottiJ. CulottiM. Genetic control of the cell division cycle in yeast: V. genetic analysis of cdc mutants.Genetics197374226728610.1093/genetics/74.2.26717248617
     [Google Scholar]
  22. HartwellL.H. CulottiJ. PringleJ.R. ReidB.J. Genetic control of the cell division cycle in yeast.Science19741834120465110.1126/science.183.4120.464587263
     [Google Scholar]
  23. NurseP. Fission yeast cell cycle mutants and the logic of eukaryotic cell cycle control.Mol. Biol. Cell202031262871287310.1091/mbc.E20‑10‑062333320707
     [Google Scholar]
  24. LiuJ. KipreosE.T. Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs): differential conservation of CAKs in yeast and metazoa.Mol. Biol. Evol.20001771061107410.1093/oxfordjournals.molbev.a02638710889219
     [Google Scholar]
  25. MalumbresM. Cyclin-dependent kinases.Genome Biol.201415612210.1186/gb418425180339
     [Google Scholar]
  26. KingR.W. JacksonP.K. KirschnerM.W. Mitosis in transition.Cell199479456357110.1016/0092‑8674(94)90542‑87954823
     [Google Scholar]
  27. SherrC.J. G1 phase progression: Cycling on cue.Cell199479455155510.1016/0092‑8674(94)90540‑17954821
     [Google Scholar]
  28. StillmanB. Cell cycle control of DNA replication.Science199627452931659166310.1126/science.274.5293.16598939847
     [Google Scholar]
  29. HardcastleI.R. GoldingB.T. GriffinR.J. Designing inhibitors of cyclin-dependent kinases.Annu. Rev. Pharmacol. Toxicol.200242132534810.1146/annurev.pharmtox.42.090601.12594011807175
     [Google Scholar]
  30. SongX. FangC. DaiY. SunY. QiuC. LinX. XuR. Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer.Br. J. Cancer202413081239124810.1038/s41416‑024‑02589‑838355840
     [Google Scholar]
  31. OffermannA. JoergV. BeckerF. RoeschM.C. KangD. LemsterA.L. TharunL. BehrendsJ. MerseburgerA.S. CuligZ. SailerV. BrägelmannJ. KirfelJ. PernerS. Inhibition of cyclin-dependent kinase 8/cyclin-dependent kinase 19 suppresses its pro-oncogenic effects in prostate cancer.Am. J. Pathol.2022192581382310.1016/j.ajpath.2022.01.01035181333
     [Google Scholar]
  32. MounikaP. GurupadayyaB. KumarH.Y. NamithaB. An overview of CDK enzyme inhibitors in cancer therapy.Curr. Cancer Drug Targets202323860361910.2174/156800962366623032014471336959160
     [Google Scholar]
  33. ŁukasikP. ZałuskiM. GutowskaI. Cyclin-Dependent Kinases (CDK) and their role in diseases development–review.Int. J. Mol. Sci.2021226293510.3390/ijms2206293533805800
     [Google Scholar]
  34. QuandtE. RibeiroM.P.C. ClotetJ. Atypical cyclins: the extended family portrait.Cell. Mol. Life Sci.202077223124210.1007/s00018‑019‑03262‑731420702
     [Google Scholar]
  35. MassacciG. PerfettoL. SaccoF. The Cyclin-dependent kinase 1: more than a cell cycle regulator.Br. J. Cancer2023129111707171610.1038/s41416‑023‑02468‑837898722
     [Google Scholar]
  36. DoP.A. LeeC.H. The role of CDK5 in tumours and tumour microenvironments.Cancers202013110110.3390/cancers1301010133396266
     [Google Scholar]
  37. SinghK. Cyclin dependent kinase as significant target for cancer treatment.CCTR20128322523510.2174/157339412802653164
     [Google Scholar]
  38. WeiP. GarberM.E. FangS.M. FischerW.H. JonesK.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.Cell199892445146210.1016/S0092‑8674(00)80939‑39491887
     [Google Scholar]
  39. YangX. GoldM.O. TangD.N. LewisD.E. Aguilar- CordovaE. RiceA.P. HerrmannC.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. USA19979423123311233610.1073/pnas.94.23.123319356449
     [Google Scholar]
  40. ManceboH.S.Y. LeeG. FlygareJ. TomassiniJ. LuuP. ZhuY. PengJ. BlauC. HazudaD. PriceD. FloresO. P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro.Genes Dev.199711202633264410.1101/gad.11.20.26339334326
     [Google Scholar]
  41. ClarkE. SantiagoF. DengL. ChongS. de la FuenteC. WangL. FuP. SteinD. DennyT. LankaV. MozafariF. OkamotoT. KashanchiF. 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.200074115040505210.1128/JVI.74.11.5040‑5052.200010799578
     [Google Scholar]
  42. PaulsE. RuizA. BadiaR. PermanyerM. GubernA. Riveira-MuñozE. Torres-TorronterasJ. ÁlvarezM. MotheB. BranderC. CrespoM. Menéndez-AriasL. ClotetB. KepplerO.T. MartíR. PosasF. BallanaE. EstéJ.A. Cell cycle control and HIV-1 susceptibility are linked by CDK6-dependent CDK2 phosphorylation of SAMHD1 in myeloid and lymphoid cells.J. Immunol.201419341988199710.4049/jimmunol.140087325015816
     [Google Scholar]
  43. CribierA. DescoursB. ValadãoA.L.C. LaguetteN. BenkiraneM. Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction activity toward HIV-1.Cell Rep.2013341036104310.1016/j.celrep.2013.03.01723602554
     [Google Scholar]
  44. BallanaE. EstéJ.A. SAMHD1: at the crossroads of cell proliferation, immune responses, and virus restriction.Trends Microbiol.2015231168069210.1016/j.tim.2015.08.00226439297
     [Google Scholar]
  45. RuizA. PaulsE. BadiaR. Torres-TorronterasJ. Riveira-MuñozE. ClotetB. MartíR. BallanaE. EstéJ.A. Cyclin D3-dependent control of the dNTP pool and HIV-1 replication in human macrophages.Cell Cycle201514111657166510.1080/15384101.2015.103055825927932
     [Google Scholar]
  46. MartinatC. CormierA. Tobaly-TapieroJ. PalmicN. CasartelliN. MahboubiB. CogginsS.A.A. BuchrieserJ. PersaudM. Diaz-GrifferoF. EspertL. BossisG. LesageP. SchwartzO. KimB. Margottin-GoguetF. SaïbA. ZamborliniA. SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells.Nat. Commun.2021121458210.1038/s41467‑021‑24802‑534321470
     [Google Scholar]
  47. GuoS. LeiX. ChangY. ZhaoJ. WangJ. DongX. LiuQ. ZhangZ. WangL. YiD. MaL. LiQ. ZhangY. DingJ. LiangC. LiX. GuoF. WangJ. CenS. SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.Signal Transduct. Target. Ther.20227140010.1038/s41392‑022‑01239‑w36575184
     [Google Scholar]
  48. IzumiyaY. LinS.F. EllisonT.J. LevyA.M. MayeurG.L. IzumiyaC. KungH.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.200377179652966110.1128/JVI.77.17.9652‑9661.200312915577
     [Google Scholar]
  49. SaxenaN. KumarV. 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 One2014910e11125610.1371/journal.pone.011125625347529
     [Google Scholar]
  50. SatoY. WatanabeT. SuzukiC. AbeY. MasudH.M.A.A. InagakiT. YoshidaM. SuzukiT. GoshimaF. AdachiJ. TomonagaT. MurataT. KimuraH. S- like-phase cyclin-dependent kinases stabilize the Epstein-Barr Virus BDLF4 protein to temporally control late gene transcription.J. Virol.2019938e01707-1810.1128/JVI.01707‑1830700607
     [Google Scholar]
  51. SchützM. CordsmeierA. WangenC. HornA.H.C. WylerE. EnsserA. StichtH. MarschallM. 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.202324241742110.3390/ijms24241742138139252
     [Google Scholar]
  52. SpazianiA. AlisiA. SannaD. BalsanoC. Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1.J. Biol. Chem.200628116109831098910.1074/jbc.M51253620016446363
     [Google Scholar]
  53. Gutierrez-ChamorroL. FelipE. EzeonwumeluI.J. MargelíM. BallanaE. Cyclin-dependent kinases as emerging targets for developing novel antiviral therapeutics.Trends Microbiol.202129983684810.1016/j.tim.2021.01.01433618979
     [Google Scholar]
  54. LiY. ZhangJ. GaoW. ZhangL. PanY. ZhangS. WangY. Insights on structural characteristics and ligand binding mechanisms of CDK2.Int. J. Mol. Sci.20151659314934010.3390/ijms1605931425918937
     [Google Scholar]
  55. PeyressatreM. PrévelC. PelleranoM. MorrisM. Targeting cyclin-dependent kinases in human cancers: from small molecules to Peptide inhibitors.Cancers (Basel)20157117923710.3390/cancers701017925625291
     [Google Scholar]
  56. KnightJ.D.R. QianB. BakerD. KotharyR. Conservation, variability and the modeling of active protein kinases.PLoS One2007210e98210.1371/journal.pone.000098217912359
     [Google Scholar]
  57. GuendelI. AgbottahE.T. Kehn-HallK. KashanchiF. Inhibition of human immunodeficiency virus type-1 by cdk inhibitors.AIDS Res. Ther.201071710.1186/1742‑6405‑7‑720334651
     [Google Scholar]
  58. SedlacekH. CzechJ. NaikR. KaurG. WorlandP. LosiewiczM. ParkerB. CarlsonB. SmithA. SenderowiczA. SausvilleE. Flavopiridol (L86 8275; NSC 649890), a new kinase inhibitor for tumor therapy.Int. J. Oncol.1996961143116810.3892/ijo.9.6.114321541623
     [Google Scholar]
  59. JulveM. ClarkJ.J. LythgoeM.P. Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma.Expert Opin. Pharmacother.202122335136110.1080/14656566.2020.182834833030382
     [Google Scholar]
  60. PerwitasariO. YanX. O’DonnellJ. JohnsonS. TrippR.A. Repurposing kinase inhibitors as antiviral agents to control Influenza A virus replication.Assay Drug Dev. Technol.2015131063864910.1089/adt.2015.0003.drrr26192013
     [Google Scholar]
  61. BadshahS.L. FaisalS. MuhammadA. PoulsonB.G. EmwasA.H. JaremkoM. Antiviral activities of flavonoids.Biomed. Pharmacother.202114011159610.1016/j.biopha.2021.11159634126315
     [Google Scholar]
  62. ChaoS.H. FujinagaK. MarionJ.E. TaubeR. SausvilleE.A. SenderowiczA.M. PeterlinB.M. PriceD.H. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication.J. Biol. Chem.200027537283452834810.1074/jbc.C00044620010906320
     [Google Scholar]
  63. SchangL.M. Discovery of the antiviral activities of pharmacologic cyclin-dependent kinase inhibitors: from basic to applied science.Expert Rev. Anti Infect. Ther.20053214514910.1586/14787210.3.2.14515918771
     [Google Scholar]
  64. HolcakovaJ. TomasecP. BugertJ.J. WangE.C.Y. WilkinsonG.W.G. HrstkaR. KrystofV. StrnadM. VojtesekB. The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties.Antivir. Chem. Chemother.201020313314210.3851/IMP146020054100
     [Google Scholar]
  65. BakerA. GregoryG.P. VerbruggeI. KatsL. HiltonJ.J. VidacsE. LeeE.M. LockR.B. ZuberJ. ShorttJ. JohnstoneR.W. The CDK9 inhibitor dinaciclib exerts potent apoptotic and antitumor effects in preclinical models of MLL-rearranged acute myeloid leukemia.Cancer Res.20167651158116910.1158/0008‑5472.CAN‑15‑107026627013
     [Google Scholar]
  66. JohnsonA.J. YehY-Y. SmithL.L. WagnerA.J. HesslerJ. GuptaS. FlynnJ. JonesJ. ZhangX. BannerjiR. GreverM.R. ByrdJ.C. The novel cyclin-dependent kinase inhibitor dinaciclib (SCH727965) promotes apoptosis and abrogates microenvironmental cytokine protection in chronic lymphocytic leukemia cells.Leukemia201226122554255710.1038/leu.2012.14422791353
     [Google Scholar]
  67. HossainD.M.S. JavaidS. CaiM. ZhangC. SawantA. HintonM. SatheM. GreinJ. BlumenscheinW. PinheiroE.M. ChackerianA. Dinaciclib induces immunogenic cell death and enhances anti-PD1–mediated tumor suppression.J. Clin. Invest.2018128264465410.1172/JCI9458629337311
     [Google Scholar]
  68. BouhaddouM. MemonD. MeyerB. WhiteK.M. RezeljV.V. Correa MarreroM. PolaccoB.J. MelnykJ.E. UlfertsS. KaakeR.M. BatraJ. RichardsA.L. StevensonE. GordonD.E. RojcA. ObernierK. FabiusJ.M. SoucherayM. MiorinL. MorenoE. KohC. TranQ.D. HardyA. RobinotR. ValletT. Nilsson-PayantB.E. Hernandez-ArmentaC. DunhamA. WeigangS. KnerrJ. ModakM. QuinteroD. ZhouY. DugourdA. ValdeolivasA. PatilT. LiQ. HüttenhainR. CakirM. MuralidharanM. KimM. JangG. TutuncuogluB. HiattJ. GuoJ.Z. XuJ. BouhaddouS. MathyC.J.P. GaultonA. MannersE.J. FélixE. ShiY. GoffM. LimJ.K. McBrideT. O’NealM.C. CaiY. ChangJ.C.J. BroadhurstD.J. KlippstenS. De witE. LeachA.R. KortemmeT. ShoichetB. OttM. Saez-RodriguezJ. tenOeverB.R. MullinsR.D. FischerE.R. KochsG. GrosseR. García-SastreA. VignuzziM. JohnsonJ.R. ShokatK.M. SwaneyD.L. BeltraoP. KroganN.J. The global phosphorylation landscape of SARS-CoV-2 infection.Cell20201823685712.e1910.1016/j.cell.2020.06.03432645325
     [Google Scholar]
  69. GargouriM. AlzwiA. AbobakerA. Cyclin dependent kinase inhibitors as a new potential therapeutic option in management of COVID-19.Med. Hypotheses202114611038010.1016/j.mehy.2020.11038033213999
     [Google Scholar]
  70. ShirsathN.P. ManoharS.M. JoshiK.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. Cancer20121117710.1186/1476‑4598‑11‑7723075291
     [Google Scholar]
  71. De AzevedoW.F.Jr Mueller-DieckmannH.J. Schulze-GahmenU. WorlandP.J. SausvilleE. KimS.H. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase.Proc. Natl. Acad. Sci. USA19969372735274010.1073/pnas.93.7.27358610110
     [Google Scholar]
  72. AlessandriA.L. DuffinR. LeitchA.E. LucasC.D. SheldrakeT.A. DorwardD.A. HiraniN. PinhoV. de SousaL.P. TeixeiraM.M. LyonsJ.F. HaslettC. RossiA.G. Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation.PLoS One201169e2568310.1371/journal.pone.002568321984938
     [Google Scholar]
  73. RigasA.C. RobsonC.N. CurtinN.J. Therapeutic potential of CDK inhibitor NU2058 in androgen-independent prostate cancer.Oncogene200726557611761910.1038/sj.onc.121058617599054
     [Google Scholar]
  74. AliA. GhoshA. NathansR.S. SharovaN. O’BrienS. CaoH. StevensonM. RanaT.M. Identification of flavopiridol analogues that selectively inhibit positive transcription elongation factor (P-TEFb) and block HIV-1 replication.ChemBioChem200910122072208010.1002/cbic.20090030319603446
     [Google Scholar]
  75. ZhangY. GuoJ. LiuY. QuY. LiY.Q. MuY. LiW. An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase.Int. J. Biol. Macromol.2024265Pt 113064410.1016/j.ijbiomac.2024.13064438462102
     [Google Scholar]
  76. SarkarA. MandalK. Repurposing an antiviral drug against SARS-CoV-2 main protease.Angew. Chem. Int. Ed.20216044234922349410.1002/anie.20210748134545983
     [Google Scholar]
  77. BogdanowB. SchmidtM. WeisbachH. GruskaI. VetterB. ImamiK. OstermannE. BruneW. SelbachM. HagemeierC. WiebuschL. Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis.Nat. Commun.2020111484510.1038/s41467‑020‑18542‑132973148
     [Google Scholar]
  78. Filgueira de AzevedoW.Jr CanduriF. Freitas da SilveiraN.J. Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol.Biochem. Biophys. Res. Commun.2002293156657110.1016/S0006‑291X(02)00266‑812054639
     [Google Scholar]
  79. ShahM. NunesM.R. StearnsV. CDK4/6 inhibitors: Game changers in the management of hormone receptor- positive advanced breast cancer?Oncology (Williston Park)201832521622229847850
     [Google Scholar]
  80. XuJ. XueY. ZhouR. ShiP.Y. LiH. ZhouJ. Drug repurposing approach to combating coronavirus: Potential drugs and drug targets.Med. Res. Rev.20214131375142610.1002/med.2176333277927
     [Google Scholar]
  81. JeonS. KoM. LeeJ. ChoiI. ByunS.Y. ParkS. ShumD. KimS. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs.Antimicrob. Agents Chemother.2020647e00819-2010.1128/AAC.00819‑2032366720
     [Google Scholar]
  82. CastellvíM. FelipE. EzeonwumeluI. BadiaR. Garcia-VidalE. PujantellM. Gutiérrez-ChamorroL. TeruelI. Martínez-CardúsA. ClotetB. Riveira-MuñozE. MargelíM. EstéJ. BallanaE. Pharmacological modulation of SAMHD1 activity by CDK4/6 inhibitors improves anticancer therapy.Cancers (Basel)202012371310.3390/cancers1203071332197329
     [Google Scholar]
  83. SchorS. EinavS. Repurposing of kinase inhibitors as broad-spectrum antiviral drugs.DNA Cell Biol.2018372636910.1089/dna.2017.403329148875
     [Google Scholar]
  84. PaulsE. BadiaR. Torres-TorronterasJ. RuizA. PermanyerM. Riveira-MuñozE. ClotetB. MartiR. BallanaE. EstéJ.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.AIDS201428152213222210.1097/QAD.000000000000039925036183
     [Google Scholar]
  85. XueY. MeiH. ChenY. GriffinJ.D. LiuQ. WeisbergE. YangJ. Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS-CoV-2.MedComm202343e25410.1002/mco2.25437193304
     [Google Scholar]
  86. Bahadur GurungA. Ajmal AliM. ElshikhM.S. ArefI. AminaM. LeeJ. 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.202229610329710.1016/j.sjbs.2022.10329735475118
     [Google Scholar]
  87. WangS. SunQ. XuY. PeiJ. LaiL. A transferable deep learning approach to fast screen potent antiviral drugs against SARS-CoV-2.bioRxiv2020202027156910.1101/2020.08.28.271569
     [Google Scholar]
  88. SyrigosG.V. FeigeM. DirlamA. BusingerR. GruskaI. WiebuschL. HamprechtK. SchindlerM. Abemaciclib restricts HCMV replication by suppressing pUL97- mediated phosphorylation of SAMHD1.Antiviral Res.202321710568910.1016/j.antiviral.2023.10568937516154
     [Google Scholar]
  89. WildM. KicuntodJ. SeylerL. WangenC. BertzbachL.D. ConradieA.M. KauferB.B. WagnerS. MichelD. EickhoffJ. TsogoevaS.B. BäuerleT. HahnF. MarschallM. Combinatorial drug treatments reveal promising anticytomegaloviral profiles for clinically relevant Pharmaceutical Kinase Inhibitors (PKIs).Int. J. Mol. Sci.202122257510.3390/ijms2202057533430060
     [Google Scholar]
  90. JiangL. YuY. LiZ. GaoY. ZhangH. ZhangM. CaoW. PengQ. ChenX. BMS-265246, a cyclin-dependent kinase inhibitor, inhibits the infection of Herpes Simplex Virus Type 1.Viruses2023158164210.3390/v1508164237631985
     [Google Scholar]
  91. FangG. ChenH. ChengZ. TangZ. WanY. Azaindole derivatives as potential kinase inhibitors and their SARs elucidation.Eur. J. Med. Chem.202325811562110.1016/j.ejmech.2023.11562137423125
     [Google Scholar]
  92. ZhaoL. YanY. DaiQ. WangZ. YinJ. XuY. WangZ. GuoX. LiW. CaoR. ZhongW. The CDK1 inhibitor, Ro-3306, is a potential antiviral candidate against influenza virus infection.Antiviral Res.202220110529610.1016/j.antiviral.2022.10529635367281
     [Google Scholar]
  93. SinghR. BhardwajV. DasP. PurohitR. Natural analogues inhibiting selective cyclin-dependent kinase protein isoforms: a computational perspective.J. Biomol. Struct. Dyn.202038175126513510.1080/07391102.2019.169670931760872
     [Google Scholar]
  94. YuD. WagnerS. SchützM. JeonY. SeoM. KimJ. BrücknerN. KicuntodJ. TillmannsJ. WangenC. HahnF. KauferB.B. NeipelF. EickhoffJ. KleblB. NamK. MarschallM. An antiherpesviral host-directed strategy based on CDK7 covalently binding drugs: Target-selective, picomolar-dose, cross-virus reactivity.Pharmaceutics202416215810.3390/pharmaceutics1602015838399219
     [Google Scholar]
  95. HuttererC. EickhoffJ. MilbradtJ. KornK. ZeitträgerI. BahsiH. WagnerS. ZischinskyG. WolfA. DegenhartC. UngerA. BaumannM. KleblB. MarschallM. A novel CDK7 inhibitor of the Pyrazolotriazine class exerts broad-spectrum antiviral activity at nanomolar concentrations.Antimicrob. Agents Chemother.20155942062207110.1128/AAC.04534‑1425624324
     [Google Scholar]
  96. YamamotoM. OnogiH. KiiI. YoshidaS. IidaK. SakaiH. AbeM. TsubotaT. ItoN. HosoyaT. HagiwaraM. CDK9 inhibitor FIT-039 prevents replication of multiple DNA viruses.J. Clin. Invest.201412483479348810.1172/JCI7380525003190
     [Google Scholar]
  97. TanakaT. Okuyama-DobashiK. MurakamiS. ChenW. OkamotoT. UedaK. HosoyaT. MatsuuraY. RyoA. TanakaY. HagiwaraM. MoriishiK. Inhibitory effect of CDK9 inhibitor FIT-039 on hepatitis B virus propagation.Antiviral Res.201613315616410.1016/j.antiviral.2016.08.00827515132
     [Google Scholar]
  98. PorterD.C. FarmakiE. AltiliaS. SchoolsG.P. WestD.K. ChenM. ChangB.D. PuzyrevA.T. LimC. Rokow-KittellR. FriedhoffL.T. PapavassiliouA.G. KalurupalleS. HurteauG. ShiJ. BaranP.S. GyorffyB. WentlandM.P. BroudeE.V. KiarisH. RoninsonI.B. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities.Proc. Natl. Acad. Sci. USA201210934137991380410.1073/pnas.120690610922869755
     [Google Scholar]
  99. KokinosE.K. TsymbalS.A. GalochkinaA.V. BezlepkinaS.A. NikolaevaJ.V. VershininaS.O. ShtroA.A. TatarskiyV.V. ShtilA.A. BroudeE.V. RoninsonI.B. DukhinovaM. Inhibition of cyclin-dependent kinases 8/19 restricts bacterial and virus-induced inflammatory responses in monocytes.Viruses2023156129210.3390/v1506129237376593
     [Google Scholar]
  100. HorvathR.M. BrummeZ.L. SadowskiI. Small molecule inhibitors of transcriptional cyclin-dependent kinases impose HIV-1 latency, presenting “block and lock” treatment strategies.Antimicrob. Agents Chemother.2024683e01072-2310.1128/aac.01072‑2338319085
     [Google Scholar]
  101. IvanovS. LaguninA. FilimonovD. TarasovaO. Network-based analysis of OMICs data to understand the HIV–host interaction.Front. Microbiol.202011131410.3389/fmicb.2020.0131432625189
     [Google Scholar]
  102. VansantG. BruggemansA. JanssensJ. DebyserZ. Block-and-lock strategies to cure HIV infection.Viruses20201218410.3390/v1201008431936859
     [Google Scholar]
  103. OlsonC.M. LiangY. LeggettA. ParkW.D. LiL. MillsC.E. ElsarragS.Z. FicarroS.B. ZhangT. DüsterR. GeyerM. SimT. MartoJ.A. SorgerP.K. WestoverK.D. LinC.Y. KwiatkowskiN. GrayN.S. Development of a selective CDK7 covalent inhibitor reveals predominant cell-cycle phenotype.Cell Chem. Biol.2019266792803.e1010.1016/j.chembiol.2019.02.01230905681
     [Google Scholar]
  104. AlbertT.K. RigaultC. EickhoffJ. BaumgartK. AntrechtC. KleblB. MittlerG. MeisterernstM. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor.Br. J. Pharmacol.20141711556810.1111/bph.1240824102143
     [Google Scholar]
  105. ClopperK.C. TaatjesD.J. Chemical inhibitors of transcription-associated kinases.Curr. Opin. Chem. Biol.20227010218610.1016/j.cbpa.2022.10218635926294
     [Google Scholar]
  106. BhurtaD. BharateS.B. Analyzing the scaffold diversity of cyclin-dependent kinase inhibitors and revisiting the clinical and preclinical pipeline.Med. Res. Rev.202242265470910.1002/med.2185634605036
     [Google Scholar]
  107. YadavR. ChaudharyJ.K. JainN. ChaudharyP.K. KhanraS. DhamijaP. SharmaA. KumarA. HanduS. Role of structural and non-structural proteins and therapeutic targets of SARS-CoV-2 for COVID-19.Cells202110482110.3390/cells1004082133917481
     [Google Scholar]
  108. ValleM. Structural homology between nucleoproteins of ssRNA viruses.Subcell. Biochem.20188812914510.1007/978‑981‑10‑8456‑0_629900495
     [Google Scholar]
  109. SaitoA. ShofaM. OdeH. YumiyaM. HiranoJ. OkamotoT. YoshimuraS.H. How do flaviviruses hijack host cell functions by phase separation?Viruses2021138147910.3390/v1308147934452345
     [Google Scholar]
  110. TavakolianS. GoudarziH. FaghihlooE. Cyclin-dependent kinases and CDK inhibitors in virus-associated cancers.Infect. Agent. Cancer20201512710.1186/s13027‑020‑00295‑732377232
     [Google Scholar]
  111. HeW. StaplesD. SmithC. FisherC. Direct activation of cyclin-dependent kinase 2 by human papillomavirus E7.J. Virol.20037719105661057410.1128/JVI.77.19.10566‑10574.200312970441
     [Google Scholar]
  112. PalA. KunduR. Human papillomavirus E6 and E7: The cervical cancer hallmarks and targets for therapy.Front. Microbiol.202010311610.3389/fmicb.2019.0311632038557
     [Google Scholar]
  113. TomaićV. Functional roles of E6 and E7 oncoproteins in HPV-induced malignancies at diverse anatomical sites.Cancers20168109510.3390/cancers810009527775564
     [Google Scholar]
  114. VatsA. Trejo-CerroO. ThomasM. BanksL. Human papillomavirus E6 and E7: What remains?Tumour Virus Research20211120021310.1016/j.tvr.2021.20021333716206
     [Google Scholar]
  115. KimJ.E.E.E.U.N. LeeJ.I.I.N. JinD.H. LeeW.J. ParkG.B. KimS. KimY.S. WuT.C. HurD.Y. KimD. 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.20143152429243710.3892/or.2014.308224627094
     [Google Scholar]
  116. KumarP. MurakamiM. KaulR. SahaA. CaiQ. RobertsonE.S. Deregulation of the cell cycle machinery by Epstein-Barr virus nuclear antigen 3C.Future Virol.200941799110.2217/17460794.4.1.7925635182
     [Google Scholar]
  117. CeresetoA. ParksR.W. RivadeneiraE. FranchiniG. Limiting amounts of p27Kip1 correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells.Oncogene199918152441245010.1038/sj.onc.120256710229195
     [Google Scholar]
  118. BaydounH.H. PancewiczJ. BaiX. NicotC. HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression.Mol. Cancer20109130210.1186/1476‑4598‑9‑30221092281
     [Google Scholar]
  119. GrassmannR. AboudM. JeangK.T. Molecular mechanisms of cellular transformation by HTLV-1 Tax.Oncogene200524395976598510.1038/sj.onc.120897816155604
     [Google Scholar]
  120. YenA. SturgillR. VarvayanisS. ChernR. FMS (CSF-1 receptor) prolongs cell cycle and promotes retinoic acid-induced hypophosphorylation of retinoblastoma protein, G1 arrest, and cell differentiation.Exp. Cell Res.1996229111112510.1006/excr.1996.03498940255
     [Google Scholar]
  121. BouchardM. GiannakopoulosS. WangE.H. TaneseN. SchneiderR.J. HepatitisB. Hepatitis B virus HBx protein activation of cyclin A-cyclin-dependent kinase 2 complexes and G1 transit via a Src kinase pathway.J. Virol.20017594247425710.1128/JVI.75.9.4247‑4257.200111287574
     [Google Scholar]
  122. BahnassyA.A. ZekriA.R.N. LoutfyS.A. MohamedW.S. MoneimA.A. SalemS.E. ShetaM.M. OmarA. Al-ZawahryH. 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.201191264365210.1016/j.yexmp.2011.06.01421801719
     [Google Scholar]
  123. TarasovaO. PoroikovV. Machine learning in discovery of new antivirals and optimization of viral infections therapy.Curr. Med. Chem.202128387840786110.2174/092986732866621050411435133949929
     [Google Scholar]
  124. WildM. HahnF. BrücknerN. SchützM. WangenC. WagnerS. SommererM. StroblS. MarschallM. Cyclin-Dependent Kinases (CDKs) and the human cytomegalovirus-encoded CDK ortholog pUL97 represent highly attractive targets for synergistic drug combinations.Int. J. Mol. Sci.2022235249310.3390/ijms2305249335269635
     [Google Scholar]
  125. JhaveriK. BurrisH.A.III YapT.A. HamiltonE. RugoH.S. GoldmanJ.W. DannS. LiuF. WongG.Y. KrupkaH. ShapiroG.I. The evolution of cyclin dependent kinase inhibitors in the treatment of cancer.Expert Rev. Anticancer Ther.202121101105112410.1080/14737140.2021.194410934176404
     [Google Scholar]
  126. OnestiC.E. JerusalemG. 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.202121328329810.1080/14737140.2021.185293433233970
     [Google Scholar]
  127. BallanaE. BadiaR. TerradasG. Torres-TorronterasJ. RuizA. PaulsE. Riveira-MuñozE. ClotetB. MartíR. EstéJ.A. SAMHD1 specifically affects the antiviral potency of thymidine analog HIV reverse transcriptase inhibitors.Antimicrob. Agents Chemother.20145884804481310.1128/AAC.03145‑1424913159
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673334631241208131015
Loading
Cyclin Dependent Kinases in Antiviral Drug Discovery
Curr. Med. Chem. 32, 7458 (2025); https://doi.org/10.2174/0109298673334631241208131015
/content/journals/cmc/10.2174/0109298673334631241208131015
/content/journals/cmc/10.2174/0109298673334631241208131015
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): anti-inflammatory drugs; antiviral drugs; Cyclin-dependent kinase; inhibitors; pharmacological agents; transcriptional regulation; viral infections

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test