An Overview of Drug Resistance in Protozoal Diseases

Capela, Rúben A.; Moreira, Rui; Lopes, Francisca

doi:10.3390/ijms20225748

Cited by 141 publications

(134 citation statements)

References 142 publications

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“…UNA also has the potential to treat various human diseases other than cancer ( Figure 3). Protozoa are composed of a wide range of unicellular living organisms, and there are diverse types of protozoa which can infect humans through various ways of transmission, such as direct, humanto-human, and fecal-oral routes [61]. Major human diseases caused by protozoa are malaria, African trypanosomiasis, Chagas' disease, leishmaniasis, and other intestinal protozoal diseases, such as amoebic dysentery and toxoplasmosis [61].…”

Section: Antiprotozoan Effectsmentioning

confidence: 99%

Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Son

Lee

2020

Biomolecules

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Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.

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Section: Antiprotozoan Effectsmentioning

confidence: 99%

Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Son

Lee

2020

Biomolecules

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“…Most PPDs are widely regarded as povertyrelated and as neglected tropical diseases, largely ignored for many years by health authorities, pharmaceutical companies and the media. It is perhaps not surprising that with such a low profile, drugs, vaccines, surveillance and control tools are lacking for most of these diseases and disease control remains problematic [6][7][8][9][10][11]. New approaches to chemotherapy are needed urgently, involving combination therapies and other strategies, in addition to cheaper, less toxic drugs.…”

Section: Introductionmentioning

confidence: 99%

Viruses of protozoan parasites and viral therapy: Is the time now right?

Barrow

Dujardin

Fasel

et al. 2020

Virol J

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Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

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“…Lack of vaccines, limited chemotherapy options, and the emergence of drug-resistant parasites are the challenges posed by the majority of protozoan diseases. There is a clear clinical need for the development of novel drugs targeting parasitic protozoa in order to prevent and treat these diseases [ 10 , 11 ].…”

Section: Introduction: When Parasitic Protozoa Met Ublsmentioning

confidence: 99%

Ubiquitin-Like Modifiers: Emerging Regulators of Protozoan Parasites

Karpiyevich

Artavanis‐Tsakonas

2020

Biomolecules

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Post-translational protein regulation allows for fine-tuning of cellular functions and involves a wide range of modifications, including ubiquitin and ubiquitin-like modifiers (Ubls). The dynamic balance of Ubl conjugation and removal shapes the fates of target substrates, in turn modulating various cellular processes. The mechanistic aspects of Ubl pathways and their biological roles have been largely established in yeast, plants, and mammalian cells. However, these modifiers may be utilised differently in highly specialised and divergent organisms, such as parasitic protozoa. In this review, we explore how these parasites employ Ubls, in particular SUMO, NEDD8, ATG8, ATG12, URM1, and UFM1, to regulate their unconventional cellular physiology. We discuss emerging data that provide evidence of Ubl-mediated regulation of unique parasite-specific processes, as well as the distinctive features of Ubl pathways in parasitic protozoa. We also highlight the potential to leverage these essential regulators and their cognate enzymatic machinery for development of therapeutics to protect against the diseases caused by protozoan parasites.

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An Overview of Drug Resistance in Protozoal Diseases

Cited by 141 publications

References 142 publications

Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Viruses of protozoan parasites and viral therapy: Is the time now right?

Ubiquitin-Like Modifiers: Emerging Regulators of Protozoan Parasites

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