Host-Directed Drug Therapies for leishmaniasis

Introduction: Host-targeted drugs bypass many of the problems encountered by treatments that specifically target parasites, by acting directly on host molecules or pathways that are redundant for the host but critical for a pathogen. Such approaches are likely to have less chance of developing resistance as the host molecules and processes mutate at lower rates than most pathogens. Additionally, because these drugs act on the host, these treatments may be broad-spectrum and effective against several pathogens.Description: Different strategies have been employed to identify new host targets. The more general approaches are transcriptomic and proteomic analysis as well as the assessment of microRNA, small interfering RNA (siRNA) and short hairpin RNA expression profiles. Functional genomics has also been used to study gain or loss of function by over-expressing cDNA or iRNA respectively in mammalian cells to investigate the effects of different phenotypes on the pathogenesis of intracellular pathogens. Additionally, hybrid interaction screens can be used to study protein-protein interaction between the host and the pathogen and can help identify potential host targets for drug therapy. Another method used to identify protein-RNA interactions is affinity chromatography.Discussion and conclusion: Despite the high prevalence of leishmaniasis, a tropical parasitic infection, only a handful of treatments available against this parasite (Sbv, miltefosine and amphotericin B). Many of those exhibit high toxicity and increasing parasitic resistance. Recent studies have identified several host-targeted therapeutics. These approaches include the use of immuno-modulators, kinase inhibitors, and also natural compounds, which activate pro-inflammatory transcription factors like NF-Kb. In these treatments, immunomodulators are promising therapeutics not only used by themselves but also in combination with other drugs.Based on what has been said, some discovered drugs are:

کلیدواژه ها:

Imatinib ، Phosphoinositide 3-kinase γ (PI3Kγ) ، AS101 (ammonium trichloro [1 ، 2-ethanediolato-O ، O’]-tellurate) ، Ibrutinib ، Berberine chloride ، Statins ، Naloxonazine ، Pentalinonsterol ، Oleuropeinis ، Mahanine ، Fucoidan ، Artemisinin ، Eugenol ، Propolis