Hepatitis D future or investigational therapies
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Hepatitis D |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2] Jolanta Marszalek, M.D. [3]
Overview
Future or Investigational Therapies
Although the lack of viral enzymes represents a challenge in the development of antiviral drugs, the life cycle of HDV relies deeply on postranslational modification and viral assembly. Therefore, these two steps are potential targets of antiviral drugs.[1]
Prenylation inhibitors are one example of antiviral drugs that target HDV replication cycle. These drugs have been used in cancer treatment, and are now being studied for hepatitis D treatment.[2]
The dependence of HDV on previous or concomitant infection of the hepatocyte by HBV, makes this another potential target for antiviral treatments. Myrcludex B (entry inhibitor of hepatitis B) was shown to be able to inhibit infection of the host cell by HBV in in vitro models and in vivo mice, consequently preventing infeccion by HDV. The drugs is currently in the trial phase.[3][4]
Other potential antiviral target is the optimization of current treatments, such as interferons, or TLR agonists. A commonly used interferon is the type I interferon, which has receptors in several different cells across the body, which is responsible for its many side-effects. Other potential interferon, with less side effects is the interferon-lambda. Because its receptors are less expressed in other cells, interferon-lambda, already being tested for hepatitis C, represents an alternative treatment for patients with hepatitis B and delta.[5]
References
- ↑ Heidrich B, Manns MP, Wedemeyer H (2013). "Treatment options for hepatitis delta virus infection". Curr Infect Dis Rep. 15 (1): 31–8. doi:10.1007/s11908-012-0307-z. PMID 23242761.
- ↑ Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL; et al. (2003). "In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus". J Clin Invest. 112 (3): 407–14. doi:10.1172/JCI17704. PMC 166292. PMID 12897208.
- ↑ Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, von Weizsäcker F; et al. (2008). "Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein". Nat Biotechnol. 26 (3): 335–41. doi:10.1038/nbt1389. PMID 18297057.
- ↑ Lütgehetmann M, Mancke LV, Volz T, Helbig M, Allweiss L, Bornscheuer T; et al. (2012). "Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation". Hepatology. 55 (3): 685–94. doi:10.1002/hep.24758. PMID 22031488.
- ↑ Muir AJ, Shiffman ML, Zaman A, Yoffe B, de la Torre A, Flamm S; et al. (2010). "Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection". Hepatology. 52 (3): 822–32. doi:10.1002/hep.23743. PMID 20564352.