MK-608 explained

MK-608 (7-deaza-2’-C-methyladenosine, 7DMA) is an antiviral drug, an adenosine analog (a type of nucleoside analog). It was originally developed by Merck & Co. as a treatment for hepatitis C, but despite promising results in animal studies,[1] [2] it was ultimately unsuccessful in clinical trials.[3] Subsequently it has been widely used in antiviral research and has shown activity against a range of viruses, including Dengue fever,[4] tick-borne encephalitis virus,[5] poliovirus,[6] [7] and most recently Zika virus,[8] [9] in both in vitro and animal models. Since it has already failed in human clinical trials previously, it is unlikely MK-608 itself will be developed as an antiviral medication, but the continuing lack of treatment options for these emerging viral diseases means that much research continues using MK-608 and related antiviral drugs.[10]

See also

Notes and References

  1. Carroll SS, Ludmerer S, Handt L, Koeplinger K, Zhang NR, Graham D, Davies ME, MacCoss M, Hazuda D, Olsen DB . 6 . Robust antiviral efficacy upon administration of a nucleoside analog to hepatitis C virus-infected chimpanzees . Antimicrobial Agents and Chemotherapy . 53 . 3 . 926–34 . March 2009 . 19075052 . 2650549 . 10.1128/AAC.01032-08 .
  2. Olsen DB, Davies ME, Handt L, Koeplinger K, Zhang NR, Ludmerer SW, Graham D, Liverton N, MacCoss M, Hazuda D, Carroll SS . 6 . Sustained viral response in a hepatitis C virus-infected chimpanzee via a combination of direct-acting antiviral agents . Antimicrobial Agents and Chemotherapy . 55 . 2 . 937–9 . February 2011 . 21115793 . 3028818 . 10.1128/AAC.00990-10 .
  3. Arnold JJ, Sharma SD, Feng JY, Ray AS, Smidansky ED, Kireeva ML, Cho A, Perry J, Vela JE, Park Y, Xu Y, Tian Y, Babusis D, Barauskus O, Peterson BR, Gnatt A, Kashlev M, Zhong W, Cameron CE . 6 . Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides . PLOS Pathogens . 8 . 11 . e1003030 . 2012 . 23166498 . 3499576 . 10.1371/journal.ppat.1003030 . free .
  4. Schul W, Liu W, Xu HY, Flamand M, Vasudevan SG . A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs . The Journal of Infectious Diseases . 195 . 5 . 665–74 . March 2007 . 17262707 . 10.1086/511310 . free .
  5. Eyer L, Valdés JJ, Gil VA, Nencka R, Hřebabecký H, Šála M, Salát J, Černý J, Palus M, De Clercq E, Růžek D . 6 . Nucleoside inhibitors of tick-borne encephalitis virus . Antimicrobial Agents and Chemotherapy . 59 . 9 . 5483–93 . September 2015 . 26124166 . 4538560 . 10.1128/AAC.00807-15 .
  6. Goris N, De Palma A, Toussaint JF, Musch I, Neyts J, De Clercq K . 2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus . Antiviral Research . 73 . 3 . 161–8 . March 2007 . 17055073 . 10.1016/j.antiviral.2006.09.007 .
  7. Wu R, Smidansky ED, Oh HS, Takhampunya R, Padmanabhan R, Cameron CE, Peterson BR . Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses . Journal of Medicinal Chemistry . 53 . 22 . 7958–66 . November 2010 . 20964406 . 2990348 . 10.1021/jm100593s . Craig Cameron (scientist) .
  8. Eyer L, Nencka R, Huvarová I, Palus M, Joao Alves M, Gould EA, De Clercq E, Růžek D . 6 . Nucleoside Inhibitors of Zika Virus . The Journal of Infectious Diseases . 214 . 5 . 707–11 . September 2016 . 27234417 . 10.1093/infdis/jiw226 . free .
  9. Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJ, Neyts J . The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model . PLOS Neglected Tropical Diseases . 10 . 5 . e0004695 . May 2016 . 27163257 . 4862633 . 10.1371/journal.pntd.0004695 . free .
  10. Vittori S, Dal Ben D, Lambertucci C, Marucci G, Volpini R, Cristalli G . Antiviral properties of deazaadenine nucleoside derivatives . Current Medicinal Chemistry . 13 . 29 . 3529–52 . 2006 . 17168721 . 10.2174/092986706779026228 .

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