Iminosugar 1-Deoxynojirimycin (DNJ) sebagai Antiviral Infeksi Virus Dengue

  • Muhammad Luthfi Adnan Fakultas Kedokteran, Universitas Islam Indonesia, Jl.Kaliurang KM.14,5 Yogyakarta-Indonesia 55584
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Keywords: antiviral, dengue, iminosugar, therapy


Abstract— Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) caused by the DENV virus are among the global problems regarding mosquito-borne viral infections. The DENV virus is transmitted through Aedes aegypti causing clinical manifestations that can cause critical illness for patients. The need for effective antiviral therapy is needed to treat DENV virus infections. 1-Deoxynojirimycin (DNJ), one of the many imino sugars found in mulberry leaves and several strains of bacteria, has potential as an antiviral against DENV virus infection. The antiviral activity of DNJ works as an inhibitor of the α-glucosidase enzyme which is important in virus secretion so that it affects the infection rate. DNJ also has the effect of boosting the immune system to initiate an immune response to a viral infection. Further research is needed to develop DNJ as an effective antiviral DENV in the future.
Keywords: antiviral, dengue, iminosugar, therapy

Abstrak— Dengue fever (DF), dengue hemorraghic fever (DHF), dan dengue shock syndrome (DSS) yang disebabkan oleh virus DENV merupakan salah satu permasalahan global mengenai infeksi virus. Virus DENV ditularkan melalui Aedes aegypti menyebabkan manifestasi klinis yang dapat menimbulkan kesakiatn kritis bagi pasien. kebutuhan terapi antiviral yang efektif diperlukan untuk mengobati infeksi virus DENV. 1-Deoxynojirimycin (DNJ), salah satu iminosugar yang banyak terdapat pada daun mulberry dan beberapa strain bakteri, memiliki potensi sebagai antiviral terhadap infeksi virus DENV. Aktivitas antiviral DNJ bekerja sebagai penghambat enzim α-glukosidase yang penting dalam sekresi virus sehingga mempengaruhi tingkat infeksi. DNJ juga memiliki efek meningkatkan sistem imun untuk menginisiasi respon imun terhadap infeksi virus. Penelitian lebih lanjut diperlukan untuk mengembangkan DNJ sebagai antiviral DENV yang efektif di masa depan.
Kata kunci: antiviral, dengue, iminosugar, therapy


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  1. Harapan H, Michie A, Mudatsir M, Sasmono RT, Imrie A. Epidemiology of dengue hemorrhagic fever in Indonesia: Analysis of five decades data from the National Disease Surveillance. BMC Res Notes [Internet]. 2019;12(1):4–9.

  2. Low JGH, Ooi EE, Vasudevan SG. Current status of dengue therapeutics research and development. J Infect Dis. 2017;215(Suppl 2):S96–102.

  3. Nguyen NM, Kien DTH, Tuan TV, Quyen NTH, Tran CNB, Thi LV, et al. Host and viral features of human dengue cases shape the population of infected and infectious Aedes aegypti mosquitoes. Proc Natl Acad Sci U S A. 2013;110(22):9072–7.

  4. Overgaard HJ, Olano VA, Jaramillo JF, Matiz MI, Sarmiento D, Stenström TA, et al. A cross-sectional survey of Aedes aegypti immature abundance in urban and rural household containers in central Colombia. Parasites and Vectors. 2017;10(1):1–12.

  5. Tuiskunen Bäck A, Lundkvist Å. Dengue viruses – an overview. Infect Ecol Epidemiol. 2013;3(1):19839.

  6. Saiz JC, de Oya NJ, Blázquez AB, Escribano-Romero E, Martín-Acebes MA. Host-directed antivirals: A realistic alternative to fight zika virus. Viruses. 2018;10(9).

  7. Li DK, Chung RT. Overview of Direct-Acting Antiviral Drugs and Drug Resistance of Hepatitis C Virus. Methods Mol Biol [Internet]. 2019;1911:3–32.

  8. Richman DD, Nathanson N. Antiviral Therapy. Viral Pathog. 2016;2016:271–287.

  9. Esposito A, D’alonzo D, De Fenza M, De Gregorio E, Tamanini A, Lippi G, et al. Synthesis and therapeutic applications of iminosugars in cystic fibrosis. Int J Mol Sci. 2020;21(9).

  10. Chang J, Block TM, Guo JT. Antiviral therapies targeting host ER alpha-glucosidases: Current status and future directions. Antiviral Res [Internet]. 2013;99(3):251–60.

  11. Andrade EHP, Figueiredo LB, Vilela APP, Rosa JCC, Oliveira JG, Zibaoui HM, et al. Spatial-temporal co-circulation of dengue virus 1, 2, 3, and 4 associated with coinfection cases in a hyperendemic area of Brazil: A 4-week survey. Am J Trop Med Hyg. 2016;94(5):1080–4.

  12. Rodenhuis-Zybert IA, Wilschut J, Smit JM. Dengue virus life cycle: Viral and host factors modulating infectivity. Cell Mol Life Sci. 2010;67(16):2773–86.

  13. Guzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Prim [Internet]. 2016;2:1–26.

  14. McLaughlin M, Vandenbroeck K. The endoplasmic reticulum protein folding factory and its chaperones: New targets for drug discovery? Br J Pharmacol. 2011;162(2):328–45.

  15. Srikiatkhachorn A, Mathew A, Rothman AL. Immune-mediated cytokine storm and its role in severe dengue. Semin Immunopathol. 2017;39(5):563–74.

  16. Vogt MB, Lahon A, Arya RP, Clinton JLS, Rico-Hesse R. Dengue viruses infect human megakaryocytes, with probable clinical consequences. PLoS Negl Trop Dis. 2019;13(11):1–23.

  17. Sutherland MR, Simon AY, Serrano K, Schubert P, Acker JP, Pryzdial ELG. Dengue virus persists and replicates during storage of platelet and red blood cell units. Transfusion. 2016;56(5):1129–37.

  18. Pozzetto B, Memmi M, Garraud O. Is transfusion-transmitted dengue fever a potential public health threat? World J Virol. 2015;4(2):113.

  19. Zhang W, Mu W, Wu H, Liang Z. An overview of the biological production of 1-deoxynojirimycin: current status and future perspective. Appl Microbiol Biotechnol. 2019;103(23–24):9335–44.

  20. Gao K, Zheng C, Wang T, Zhao H, Wang J, Wang Z, et al. 1-Deoxynojirimycin: Occurrence, extraction, chemistry, oral pharmacokinetics, biological activities and in silico target fishing. Molecules. 2016;21(11).

  21. Hu XQ, Thakur K, Chen GH, Hu F, Zhang JG, Zhang H Bin, et al. Metabolic Effect of 1-Deoxynojirimycin from Mulberry Leaves on db/db Diabetic Mice Using Liquid Chromatography-Mass Spectrometry Based Metabolomics. Vol. 65, Journal of Agricultural and Food Chemistry. 2017. 4658–4667 p.

  22. Foucart Q, Shimadate Y, Marrot J, Kato A, Désiré J, Blériot Y. Synthesis and glycosidase inhibition of conformationally locked DNJ and DMJ derivatives exploiting a 2-oxo-C -allyl iminosugar. Org Biomol Chem. 2019;17(30):7204–14.

  23. Li YG, Ji DF, Zhong S, Lin TB, Lv ZQ, Hu GY, et al. 1-Deoxynojirimycin Inhibits Glucose Absorption and Accelerates Glucose Metabolism in Streptozotocin-Induced Diabetic Mice. Sci Rep. 2013;3:1–12.

  24. Li AN, Chen JJ, Li QQ, Zeng GY, Chen QY, Chen JL, et al. Alpha-glucosidase inhibitor 1-Deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK. Biochem Biophys Res Commun. 2019;509(4):1001–7.

  25. Hussain S, Miller JL, Harvey DJ, Gu Y, Rosenthal PB, Zitzmann N, et al. Strain-specific antiviral activity of iminosugars against human influenza A viruses. J Antimicrob Chemother. 2015;70(1):136–52.

  26. Stavale EJ, Vu H, Sampath A, Ramstedt U, Warfield KL. In vivo therapeutic protection against influenza a (H1N1) oseltamivir-sensitive and resistant viruses by the iminosugar UV-4. PLoS One. 2015;10(3):1–14.

  27. Alonzi DS, Scott KA, Dwek RA, Zitzmann N. Iminosugar antivirals: The therapeutic sweet spot. Biochem Soc Trans. 2017;45(2):571–82.

  28. Wang R, Li Y, Mu W, Li Z, Sun J, Wang B, et al. Mulberry leaf extract reduces the glycemic indexes of four common dietary carbohydrates. Med (United States). 2018;97(34).

  29. Kothari S, Saravana M, Muthusamy S, Mozingo A, Soni M. Safety assessment of a standardized cucumber extract (Q-ActinTM): Oral repeat-dose toxicity and mutagenicity studies. Toxicol Reports [Internet]. 2018;5(August):1078–86.

  30. Tyrrell BE, Sayce AC, Warfield KL, Miller JL, Zitzmann N. Iminosugars: Promising therapeutics for influenza infection. Crit Rev Microbiol. 2017;43(5):521–45.

  31. Howe JD, Smith N, Lee MJR, Ardes-Guisot N, Vauzeilles B, Désiré J, et al. Novel imino sugar α-glucosidase inhibitors as antiviral compounds. Bioorganic Med Chem [Internet]. 2013;21(16):4831–8.

  32. Kiappes JL, Hill ML, Alonzi DS, Miller JL, Iwaki R, Sayce AC, et al. ToP-DNJ, a Selective Inhibitor of Endoplasmic Reticulum α-Glucosidase II Exhibiting Antiflaviviral Activity. ACS Chem Biol. 2018;13(1):60–5.

  33. Zhao X, Guo F, Comunale MA, Mehta A, Sehgal M, Jain P, et al. Inhibition of endoplasmic reticulum-resident glucosidases impairs severe acute respiratory syndrome coronavirus and human coronavirus NL63 spike protein-mediated entry by altering the glycan processing of angiotensin I-converting enzyme 2. Antimicrob Agents Chemother. 2015;59(1):206–16.

  34. Sayce AC, Alonzi DS, Killingbeck SS, Tyrrell BE, Hill ML, Caputo AT, et al. Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases—Not Glycolipid Processing Enzymes. PLoS Negl Trop Dis. 2016;10(3):1–22.

  35. Alonzi DS, Kukushkin N V., Allman SA, Hakki Z, Williams SJ, Pierce L, et al. Glycoprotein misfolding in the endoplasmic reticulum: Identification of released oligosaccharides reveals a second ER-associated degradation pathway for Golgi-retrieved proteins. Cell Mol Life Sci. 2013;70(15):2799–814.

  36. Diwaker D, Mishra KP, Ganju L. Effect of modulation of unfolded protein response pathway on dengue virus infection. Acta Biochim Biophys Sin (Shanghai). 2015;47(12):960–8.
  37. Bhushan G, Lim L, Bird I, Chothe SK, Nissly RH, Kuchipudi S V. Iminosugars With Endoplasmic Reticulum α-Glucosidase Inhibitor Activity Inhibit ZIKV Replication and Reverse Cytopathogenicity in vitro. Front Microbiol. 2020;11(February 2016):1–15.

  38. Chan CYY, Low JZH, Gan ES, Ong EZ, Zhang SL-X, Tan HC, et al. Antibody-Dependent Dengue Virus Entry Modulates Cell Intrinsic Responses for Enhanced Infection. mSphere. 2019;4(5).

  39. Takeda K, Qin SY, Matsumoto N, Yamamoto K. Association of malectin with ribophorin I is crucial for attenuation of misfolded glycoprotein secretion. Biochem Biophys Res Commun [Internet]. 2014;454(3):436–40.

  40. O’Keefe S, Roebuck QP, Nakagome I, Hirono S, Kato A, Nash R, et al. Characterizing the selectivity of ER α-glucosidase inhibitors. Glycobiology. 2019;29(7):530–42.

  41. St. John AL, Rathore APS. Adaptive immune responses to primary and secondary dengue virus infections. Nat Rev Immunol [Internet]. 2019;19(4):218–30.

  42. Gack MU, Diamond MS. Innate immune escape by Dengue and West Nile viruses. Curr Opin Virol. 2016;20(October):119–128.

  43. Miller JL, Hill ML, Brun J, Pountain A, Sayce AC, Zitzmann N. Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus. Vol. 170, Antiviral Research. 2019.

  44. Castillo Ramirez JA, Urcuqui-Inchima S. Dengue Virus Control of Type i IFN Responses: A History of Manipulation and Control. J Interf Cytokine Res. 2015;35(6):421–30.

  45. Chang J, Schul W, Yip A, Xu X, Guo JT, Block TM. Competitive inhibitor of cellular α-glucosidases protects mice from lethal dengue virus infection. Antiviral Res [Internet]. 2011;92(2):369–71.

  46. Warfield KL, Alonzi DS, Hill JC, Caputo AT, Roversi P, Kiappes JL, et al. Targeting Endoplasmic Reticulum α-Glucosidase i with a Single-Dose Iminosugar Treatment Protects against Lethal Influenza and Dengue Virus Infections. J Med Chem. 2020;63(8):4205–14.

How to Cite
Adnan, M. L. (2020). Iminosugar 1-Deoxynojirimycin (DNJ) sebagai Antiviral Infeksi Virus Dengue. Keluwih: Jurnal Kesehatan Dan Kedokteran, 2(1), 56-63.