1887

Abstract

Antiviral therapy for human cytomegalovirus (HCMV) currently relies upon direct-acting antiviral drugs. However, it is now well known that these drugs have shortcomings, which limit their use. Here I review the identification and investigation of compounds targeting cellular proteins that have anti-HCMV activity and could supersede those anti-HCMV drugs currently in use. This includes discussion of drug repurposing, for example the use of artemisinin compounds, and discussion of new directions to identify compounds that target cellular factors in HCMV-infected cells, for example screening of kinase inhibitors. In addition, I highlight developing areas such as the use of machine learning and emphasize how interaction with fields outside virology will be critical for development of anti-HCMV compounds.

Funding
This study was supported by the:
  • St. George's, University of London
    • Principle Award Recipient: BlairL Strang
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-10-10
2023-01-28
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References

  1. Griffiths PD. Burden of disease associated with human cytomegalovirus and prospects for elimination by universal immunisation. Lancet Infect Dis 2012; 12:790–798 [View Article]
    [Google Scholar]
  2. Coyne CB, Lazear HM. Zika virus - reigniting the TORCH. Nat Rev Microbiol 2016; 14:707–715 [View Article]
    [Google Scholar]
  3. Mack I, Burckhardt M-A, Heininger U, Prüfer F, Schulzke S et al. Symptomatic congenital cytomegalovirus infection in children of seropositive women. Front Pediatr 2017; 5:134 [View Article]
    [Google Scholar]
  4. Griffiths P, Baraniak I, Reeves M. The pathogenesis of human cytomegalovirus. J Pathol 2015; 235:288–297 [View Article]
    [Google Scholar]
  5. Griffiths PD. CMV as a cofactor enhancing progression of AIDS. J Clin Virol 2006; 35:489–492 [View Article]
    [Google Scholar]
  6. Cheng J, Ke Q, Jin Z, Wang H, Kocher O et al. Cytomegalovirus infection causes an increase of arterial blood pressure. PLoS Pathog 2009; 5:e1000427 [View Article]
    [Google Scholar]
  7. Müller J, Tanner R, Matsumiya M, Snowden MA, Landry B et al. Cytomegalovirus infection is a risk factor for tuberculosis disease in infants. JCI Insight 2019; 4:23 [View Article]
    [Google Scholar]
  8. Savva GM, Pachnio A, Kaul B, Morgan K, Huppert FA et al. Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell 2013; 12:381–387 [View Article]
    [Google Scholar]
  9. Griffiths P. The direct and indirect consequences of cytomegalovirus infection and potential benefits of vaccination. Antiviral Res 2020; 176:104732 [View Article]
    [Google Scholar]
  10. Griffiths P. New vaccines and antiviral drugs for cytomegalovirus. J Clin Virol 2019; 116:58–61 [View Article]
    [Google Scholar]
  11. Griffiths P, Reeves M. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nat Rev Microbiol 2021; 19:759–773 [View Article]
    [Google Scholar]
  12. Webster H, Valencia S, Kumar A, Chan C, Dennis M et al. Pre-existing immunity to cytomegalovirus in macaques influences human CMV vaccine responses in preclinical models. Vaccine 2021; 39:5358–5367 [View Article]
    [Google Scholar]
  13. Kaufmann SHE, Dorhoi A, Hotchkiss RS, Bartenschlager R. Host-directed therapies for bacterial and viral infections. Nat Rev Drug Discov 2018; 17:35–56 [View Article]
    [Google Scholar]
  14. Kumar N, Sharma S, Kumar R, Tripathi BN, Barua S et al. Host-directed antiviral therapy. Clin Microbiol Rev 2020; 33:e00168-19 [View Article]
    [Google Scholar]
  15. White KM, Rosales R, Yildiz S, Kehrer T, Miorin L et al. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science 2021; 371:926–931 [View Article]
    [Google Scholar]
  16. Varona JF, Landete P, Lopez-Martin JA, Estrada V, Paredes R et al. Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19. Life Sci Alliance 2022; 5:e202101200 [View Article]
    [Google Scholar]
  17. De Clercq E, Sakuma T, Baba M, Pauwels R, Balzarini J et al. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res 1987; 8:261–272 [View Article]
    [Google Scholar]
  18. Kim HT, Kim DK, Kim YW, Kim KH, Sugiyama Y et al. Antiviral activity of 9-[[(ethoxyhydroxyphosphinyl)-methoxy]methoxy] guanine against cytomegalovirus and herpes simplex virus. Antiviral Res 1995; 28:243–251 [View Article]
    [Google Scholar]
  19. Neyts J, De Clercq E. The immunosuppressive agent mycophenolate mofetil markedly potentiates the activity of lobucavir [1R(1alpha,2beta,3alpha)]-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine against different herpes viruses. Transplantation 1999; 67:760–764 [View Article]
    [Google Scholar]
  20. Neyts J, De Clercq E. The anti-herpesvirus activity of (1’S,2’R)-9-[[1’,2’-bis(hydroxymethyl)-cycloprop-1’-yl]methyl]guanine is markedly potentiated by the immunosuppressive agent mycophenolate mofetil. Antiviral Res 2001; 49:121–127 [View Article]
    [Google Scholar]
  21. Chen H, Beardsley GP, Coen DM. Mechanism of ganciclovir-induced chain termination revealed by resistant viral polymerase mutants with reduced exonuclease activity. Proc Natl Acad Sci 2014; 111:17462–17467 [View Article]
    [Google Scholar]
  22. Chou S, Marousek GI, Senters AE, Davis MG, Biron KK. Mutations in the human cytomegalovirus UL27 gene that confer resistance to maribavir. J Virol 2004; 78:7124–7130 [View Article]
    [Google Scholar]
  23. Chou S, Wechel LCV, Marousek GI. Cytomegalovirus UL97 kinase mutations that confer maribavir resistance. J Infect Dis 2007; 196:91–94 [View Article]
    [Google Scholar]
  24. Cherrier L, Nasar A, Goodlet KJ, Nailor MD, Tokman S et al. Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection. Am J Transplant 2018; 18:3060–3064 [View Article]
    [Google Scholar]
  25. Chou S. Rapid in vitro evolution of human cytomegalovirus UL56 mutations that confer letermovir resistance. Antimicrob Agents Chemother 2015; 59:6588–6593 [View Article]
    [Google Scholar]
  26. Chou S. A third component of the human cytomegalovirus terminase complex is involved in letermovir resistance. Antiviral Res 2017; 148:1–4 [View Article]
    [Google Scholar]
  27. Chou S. Comparison of cytomegalovirus terminase gene mutations selected after exposure to three distinct inhibitor compounds. Antimicrob Agents Chemother 2017; 61:e01325-17 [View Article]
    [Google Scholar]
  28. Mercorelli B, Luganini A, Nannetti G, Tabarrini O, Palù G et al. Drug repurposing approach identifies inhibitors of the prototypic viral transcription factor IE2 that block human cytomegalovirus replication. Cell Chem Biol 2016; 23:340–351 [View Article]
    [Google Scholar]
  29. Mercorelli B, Luganini A, Muratore G, Massari S, Terlizzi ME et al. The 6-Aminoquinolone WC5 inhibits different functions of the immediate-early 2 (IE2) protein of human cytomegalovirus that are essential for viral replication. Antimicrob Agents Chemother 2014; 58:6615–6626 [View Article]
    [Google Scholar]
  30. Mercorelli B, Gribaudo G, Palù G, Loregian A. Approaches for the generation of new anti-cytomegalovirus agents: identification of protein-protein interaction inhibitors and compounds against the HCMV IE2 protein. Methods Mol Biol 2014; 1119:349–363 [View Article]
    [Google Scholar]
  31. Massari S, Mercorelli B, Sancineto L, Sabatini S, Cecchetti V et al. Design, synthesis, and evaluation of WC5 analogues as inhibitors of human cytomegalovirus immediate-early 2 protein, a promising target for anti-HCMV treatment. ChemMedChem 2013; 8:1403–1414 [View Article]
    [Google Scholar]
  32. Luganini A, Mercorelli B, Messa L, Palù G, Gribaudo G et al. The isoquinoline alkaloid berberine inhibits human cytomegalovirus replication by interfering with the viral Immediate early-2 (IE2) protein transactivating activity. Antiviral Res 2019; 164:52–60 [View Article]
    [Google Scholar]
  33. Mercorelli B, Luganini A, Celegato M, Palù G, Gribaudo G et al. Repurposing the clinically approved calcium antagonist manidipine dihydrochloride as a new early inhibitor of human cytomegalovirus targeting the Immediate-Early 2 (IE2) protein. Antiviral Res 2018; 150:130–136 [View Article]
    [Google Scholar]
  34. Vasou A, Paulus C, Narloch J, Gage ZO, Rameix-Welti M-A et al. Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice. Antiviral Res 2018; 150:79–92 [View Article]
    [Google Scholar]
  35. Coen DM, Schaffer PA. Antiherpesvirus drugs: a promising spectrum of new drugs and drug targets. Nat Rev Drug Discov 2003; 2:278–288 [View Article]
    [Google Scholar]
  36. Ghassabian H, Falchi F, Timmoneri M, Mercorelli B, Loregian A et al. Divide et impera: an in silico screening targeting HCMV ppUL44 processivity factor homodimerization identifies small molecules inhibiting viral replication. Viruses 2021; 13:941 [View Article]
    [Google Scholar]
  37. Chen H, Coseno M, Ficarro SB, Mansueto MS, Komazin-Meredith G et al. A small covalent allosteric inhibitor of human cytomegalovirus DNA polymerase subunit interactions. ACS Infect Dis 2017; 3:112–118 [View Article]
    [Google Scholar]
  38. Loregian A, Coen DM. Selective anti-cytomegalovirus compounds discovered by screening for inhibitors of subunit interactions of the viral polymerase. Chem Biol 2006; 13:191–200 [View Article]
    [Google Scholar]
  39. Sourvinos G, Tavalai N, Berndt A, Spandidos DA, Stamminger T. Recruitment of human cytomegalovirus immediate-early 2 protein onto parental viral genomes in association with ND10 in live-infected cells. J Virol 2007; 81:10123–10136 [View Article]
    [Google Scholar]
  40. Stanton RJ, Baluchova K, Dargan DJ, Cunningham C, Sheehy O et al. Reconstruction of the complete human cytomegalovirus genome in a BAC reveals RL13 to be a potent inhibitor of replication. J Clin Invest 2010; 120:3191–3208 [View Article]
    [Google Scholar]
  41. Hein MY, Weissman JS. Functional single-cell genomics of human cytomegalovirus infection. Nat Biotechnol 2022; 40:391–401 [View Article]
    [Google Scholar]
  42. Kapoor A, Cai H, Forman M, He R, Shamay M et al. Human cytomegalovirus inhibition by cardiac glycosides: evidence for involvement of the HERG gene. Antimicrob Agents Chemother 2012; 56:4891–4899 [View Article]
    [Google Scholar]
  43. Cai H, Kapoor A, He R, Venkatadri R, Forman M et al. In vitro combination of anti-cytomegalovirus compounds acting through different targets: role of the slope parameter and insights into mechanisms of action. Antimicrob Agents Chemother 2014; 58:986–994 [View Article]
    [Google Scholar]
  44. Cai H, Wang H-YL, Venkatadri R, Fu D-X, Forman M et al. Digitoxin analogues with improved anticytomegalovirus activity. ACS Med Chem Lett 2014; 5:395–399 [View Article]
    [Google Scholar]
  45. Mukhopadhyay R, Venkatadri R, Katsnelson J, Arav-Boger R. Digitoxin suppresses human cytomegalovirus replication via na(+), K(+)/atpase alpha1 subunit-dependent AMP-activated protein kinase and autophagy activation. J Virol 2018; 92: [View Article]
    [Google Scholar]
  46. Mercorelli B, Celegato M, Luganini A, Gribaudo G, Lepesheva GI et al. The antifungal drug isavuconazole inhibits the replication of human cytomegalovirus (HCMV) and acts synergistically with anti-HCMV drugs. Antiviral Res 2021; 189:105062 [View Article]
    [Google Scholar]
  47. Mercorelli B, Luganini A, Celegato M, Palù G, Gribaudo G et al. The clinically approved antifungal drug posaconazole inhibits human cytomegalovirus replication. Antimicrob Agents Chemother 2020; 64:e00056-20 [View Article]
    [Google Scholar]
  48. Marschall M, Niemann I, Kosulin K, Bootz A, Wagner S et al. Assessment of drug candidates for broad-spectrum antiviral therapy targeting cellular pyrimidine biosynthesis. Antiviral Res 2013; 100:640–648 [View Article]
    [Google Scholar]
  49. Efferth T. Beyond malaria: the inhibition of viruses by artemisinin-type compounds. Biotechnol Adv 2018; 36:1730–1737 [View Article]
    [Google Scholar]
  50. Efferth T, Marschall M, Wang X, Huong S-M, Hauber I et al. Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses. J Mol Med 2002; 80:233–242 [View Article]
    [Google Scholar]
  51. Arav-Boger R, He R, Chiou C-J, Liu J, Woodard L et al. Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. PLoS One 2010; 5:e10370 [View Article]
    [Google Scholar]
  52. He R, Mott BT, Rosenthal AS, Genna DT, Posner GH et al. An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV) and anti-cancer activities. PLoS One 2011; 6:e24334 [View Article]
    [Google Scholar]
  53. Oiknine-Djian E, Weisblum Y, Panet A, Wong HN, Haynes RK et al. The artemisinin derivative artemisone is a potent inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother 2018; 62:e00288-18 [View Article]
    [Google Scholar]
  54. Reiter C, Fröhlich T, Gruber L, Hutterer C, Marschall M et al. Highly potent artemisinin-derived dimers and trimers: synthesis and evaluation of their antimalarial, antileukemia and antiviral activities. Bioorg Med Chem 2015; 23:5452–5458 [View Article]
    [Google Scholar]
  55. Oiknine-Djian E, Bar-On S, Laskov I, Lantsberg D, Haynes RK et al. Artemisone demonstrates synergistic antiviral activity in combination with approved and experimental drugs active against human cytomegalovirus. Antiviral Res 2019; 172:104639 [View Article]
    [Google Scholar]
  56. Roy S, Kapoor A, Zhu F, Mukhopadhyay R, Ghosh AK et al. Artemisinins target the intermediate filament protein vimentin for human cytomegalovirus inhibition. J Biol Chem 2020; 295:15013–15028 [View Article]
    [Google Scholar]
  57. Hutterer C, Niemann I, Milbradt J, Fröhlich T, Reiter C et al. The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65. Antiviral Res 2015; 124:101–109 [View Article]
    [Google Scholar]
  58. Jacquet C, Marschall M, Andouard D, El Hamel C, Chianea T et al. A highly potent trimeric derivative of artesunate shows promising treatment profiles in experimental models for congenital HCMV infection in vitro and ex vivo. Antiviral Res 2020; 175:104700 [View Article]
    [Google Scholar]
  59. Hahn F, Fröhlich T, Frank T, Bertzbach LD, Kohrt S et al. Artesunate-derived monomeric, dimeric and trimeric experimental drugs - heir unique mechanistic basis and pronounced antiherpesviral activity. Antiviral Res 2018; 152:104–110 [View Article]
    [Google Scholar]
  60. Barger-Kamate B, Forman M, Sangare CO, Haidara ASA, Maiga H et al. Effect of artemether-lumefantrine (Coartem) on cytomegalovirus urine viral load during and following treatment for malaria in children. J Clin Virol 2016; 77:40–45 [View Article]
    [Google Scholar]
  61. Wolf DG, Shimoni A, Resnick IB, Stamminger T, Neumann AU et al. Human cytomegalovirus kinetics following institution of artesunate after hematopoietic stem cell transplantation. Antiviral Res 2011; 90:183–186 [View Article] [PubMed]
    [Google Scholar]
  62. Mukhopadhyay R, Roy S, Venkatadri R, Su Y-P, Ye W et al. Efficacy and mechanism of action of low dose emetine against human cytomegalovirus. PLoS Pathog 2016; 12:e1005717 [View Article]
    [Google Scholar]
  63. Gardner TJ, Cohen T, Redmann V, Lau Z, Felsenfeld D et al. Development of a high-content screen for the identification of inhibitors directed against the early steps of the cytomegalovirus infectious cycle. Antiviral Res 2015; 113:49–61 [View Article]
    [Google Scholar]
  64. Falci Finardi N, Kim H, Hernandez LZ, Russell MRG, Ho CM-K et al. Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication. J Gen Virol 2021; 102:12 [View Article]
    [Google Scholar]
  65. Nukui M, O’Connor CM, Murphy EA. The natural flavonoid compound deguelin inhibits HCMV lytic replication within fibroblasts. Viruses 2018; 10:E614 [View Article]
    [Google Scholar]
  66. Hutterer C, Wandinger SK, Wagner S, Müller R, Stamminger T et al. Profiling of the kinome of cytomegalovirus-infected cells reveals the functional importance of host kinases Aurora A, ABL and AMPK. Antiviral Res 2013; 99:139–148 [View Article]
    [Google Scholar]
  67. Mocarski ES, Shenk T, Griffiths PD, Pass RF. Cytomegaloviruses. In Knipe DM, Howley PM. eds Fields Virology, 6th ed. vol 2 New York, NY: Lippincott, Williams & Wilkins; 2015 pp 1960–2015
    [Google Scholar]
  68. Ho CMK, Donovan-Banfield IZ, Tan L, Zhang T, Gray NS et al. Inhibition of IKKα by BAY61-3606 reveals IKKα-dependent histone H3 phosphorylation in human cytomegalovirus infected cells. PLoS One 2016; 11:e0150339 [View Article]
    [Google Scholar]
  69. Arend KC, Lenarcic EM, Vincent HA, Rashid N, Lazear E et al. Kinome profiling identifies druggable targets for novel human cytomegalovirus (HCMV) antivirals. Mol Cell Proteomics 2017; 16:S263–S276 [View Article]
    [Google Scholar]
  70. Terry LJ, Vastag L, Rabinowitz JD, Shenk T. Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection. Proc Natl Acad Sci 2012; 109:3071–3076 [View Article]
    [Google Scholar]
  71. Polachek WS, Moshrif HF, Franti M, Coen DM, Sreenu VB et al. High-throughput small interfering RNA screening identifies phosphatidylinositol 3-Kinase class II alpha as important for production of human cytomegalovirus virions. J Virol 2016; 90:8360–8371 [View Article]
    [Google Scholar]
  72. Lee CH, Grey F. Systems virology and human cyytomegalovirus: using high throughput approaches to identify novel host-virus interactions during lytic nfection. Front Cell Infect Microbiol 2020; 10:280 [View Article]
    [Google Scholar]
  73. Beelontally R, Wilkie GS, Lau B, Goodmaker CJ, Ho CMK et al. Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins. Antiviral Res 2017; 138:61–67 [View Article]
    [Google Scholar]
  74. Strang BL. RO0504985 is an inhibitor of CMGC kinase proteins and has anti-human cytomegalovirus activity. Antiviral Res 2017; 144:21–26 [View Article]
    [Google Scholar]
  75. Khan AS, Murray MJ, Ho CMK, Zuercher WJ, Reeves MB et al. High-throughput screening of a GlaxoSmithKline protein kinase inhibitor set identifies an inhibitor of human cytomegalovirus replication that prevents CREB and histone H3 post-translational modification. J Gen Virol 2017; 98:754–768 [View Article]
    [Google Scholar]
  76. Elkins JM, Fedele V, Szklarz M, Abdul Azeez KR, Salah E et al. Comprehensive characterization of the published kinase inhibitor set. Nat Biotechnol 2016; 34:95–103 [View Article]
    [Google Scholar]
  77. Drewry DH, Willson TM, Zuercher WJ. Seeding collaborations to advance kinase science with the GSK published kinase inhibitor set (PKIS). Curr Top Med Chem 2014; 14:340–342 [View Article]
    [Google Scholar]
  78. Strang BL, Asquith CRM, Moshrif HF, Ho CM-K, Zuercher WJ et al. Identification of lead anti-human cytomegalovirus compounds targeting MAP4K4 via machine learning analysis of kinase inhibitor screening data. PLoS One 2018; 13:e0201321 [View Article]
    [Google Scholar]
  79. Hutterer C, Milbradt J, Hamilton S, Zaja M, Leban J et al. Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) exert a strong anti-herpesviral activity. Antiviral Res 2017; 143:113–121 [View Article]
    [Google Scholar]
  80. Al-Ali H, Lee D-H, Danzi MC, Nassif H, Gautam P et al. Rational polypharmacology: systematically identifying and engaging multiple drug targets to promote axon growth. ACS Chem Biol 2015; 10:1939–1951 [View Article]
    [Google Scholar]
  81. Barrasa MI, Harel NY, Alwine JC. The phosphorylation status of the serine-rich region of the human cytomegalovirus 86-kilodalton major immediate-early protein IE2/IEP86 affects temporal viral gene expression. J Virol 2005; 79:1428–1437 [View Article]
    [Google Scholar]
  82. Heider JA, Yu Y, Shenk T, Alwine JC. Characterization of a human cytomegalovirus with phosphorylation site mutations in the immediate-early 2 protein. J Virol 2002; 76:928–932 [View Article]
    [Google Scholar]
  83. Harel NY, Alwine JC. Phosphorylation of the human cytomegalovirus 86-kilodalton immediate-early protein IE2. J Virol 1998; 72:5481–5492 [View Article]
    [Google Scholar]
  84. Reeves MB. Chromatin-mediated regulation of cytomegalovirus gene expression. Virus Res 2011; 157:134–143 [View Article]
    [Google Scholar]
  85. Kew VG, Yuan J, Meier J, Reeves MB. Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency. PLoS Pathog 2014; 10:e1004195 [View Article]
    [Google Scholar]
  86. Naqvi S, Macdonald A, McCoy CE, Darragh J, Reith AD et al. Characterization of the cellular action of the MSK inhibitor SB-747651A. Biochem J 2012; 441:347–357 [View Article]
    [Google Scholar]
  87. Knudsen AM, Boldt HB, Jakobsen EV, Kristensen BW. The multi-target small-molecule inhibitor SB747651A shows in vitro and in vivo anticancer efficacy in glioblastomas. Sci Rep 2021; 11:6066 [View Article]
    [Google Scholar]
  88. Ferguson FM, Gray NS. Kinase inhibitors: the road ahead. Nat Rev Drug Discov 2018; 17:353–377 [View Article]
    [Google Scholar]
  89. Yakimovich A, Huttunen M, Zehnder B, Coulter LJ, Gould V et al. Inhibition of poxvirus gene expression and genome replication by bisbenzimide derivatives. J Virol 2017; 91:18 [View Article]
    [Google Scholar]
  90. Nightingale K, Lin K-M, Ravenhill BJ, Davies C, Nobre L et al. High-definition analysis of host protein stability during human cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms. Cell Host Microbe 2018; 24:447–460 [View Article]
    [Google Scholar]
  91. Nightingale K, Potts M, Hunter LM, Fielding CA, Zerbe CM et al. Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex. Proc Natl Acad Sci 2022; 119:e2108173119 [View Article]
    [Google Scholar]
  92. Le-Trilling VTK, Megger DA, Katschinski B, Landsberg CD, Rückborn MU et al. Broad and potent antiviral activity of the NAE inhibitor MLN4924. Sci Rep 2016; 6:19977 [View Article]
    [Google Scholar]
  93. Becker T, Le-Trilling VTK, Trilling M. Cellular cullin RING ubiquitin ligases: druggable host dependency factors of cytomegaloviruses. Int J Mol Sci 2019; 20:E1636 [View Article]
    [Google Scholar]
  94. Jumper J, Evans R, Pritzel A, Green T, Figurnov M et al. Highly accurate protein structure prediction with AlphaFold. Nature 2021; 596:583–589 [View Article]
    [Google Scholar]
  95. Jumper J, Hassabis D. Protein structure predictions to atomic accuracy with AlphaFold. Nat Methods 2022; 19:11–12 [View Article]
    [Google Scholar]
  96. Senior AW, Evans R, Jumper J, Kirkpatrick J, Sifre L et al. Improved protein structure prediction using potentials from deep learning. Nature 2020; 577:706–710 [View Article]
    [Google Scholar]
  97. Tunyasuvunakool K, Adler J, Wu Z, Green T, Zielinski M et al. Highly accurate protein structure prediction for the human proteome. Nature 2021; 596:590–596 [View Article]
    [Google Scholar]
  98. James SH, Price NB, Hartline CB, Lanier ER, Prichard MN. Selection and recombinant phenotyping of a novel CMX001 and cidofovir resistance mutation in human cytomegalovirus. Antimicrob Agents Chemother 2013; 57:3321–3325 [View Article]
    [Google Scholar]
  99. Reeves MB. Cell signaling and cytomegalovirus reactivation: what do Src family kinases have to do with it?. Biochem Soc Trans 2020; 48:667–675 [View Article]
    [Google Scholar]
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