New dimensions in the field of antimalarial research against malaria resurgence

Narula, Anudeep Kumar; Azad, Chandra S.; Nainwal, Lalit Mohan

doi:10.1016/j.ejmech.2019.05.043

Cited by 29 publications

(19 citation statements)

References 325 publications

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“…Invasion-associated antigens received wide attention as malaria vaccine candidates for invasion into erythrocytes is an essential step for the successful proliferation and transmission of plasmodial parasites (6,7). In particular, merozoite antigens presented on the surface and that released upon contact of the merozoite with the erythrocyte are direct targets of naturally acquired humoural immunity and hence have been extensively investigated as potential candidates in vaccine development (8).…”

Section: Introductionmentioning

confidence: 99%

Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses

Hou

Jiang

et al. 2020

Front. Immunol.

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Induction of humoural immunity is critical for clinical protection against malaria. More than 100 malaria vaccine candidates have been investigated at different developmental stages, but with limited protection. One of the roadblocks constrains the development of malaria vaccines is the poor immunogenicity of the antigens. The objective of this study was to map the linear B-cell epitopes of the Plasmodium falciparum erythrocyte invasion-associated antigens with a purpose of understanding humoural responses and protection. We conducted a large-scale screen using overlapping peptide microarrays of 37 proteins from the P. falciparum parasite, most of which are invasion-associated antigens which have been tested in clinical settings as vaccine candidates, with sera from individuals with various infection episodes. Analysis of the epitome of the antigens revealed that the most immunogenic epitopes were predominantly located in the low-complexity regions of the proteins containing repetitive and/or glutamate-rich motifs in different sequence contexts. However, in vitro assay showed the antibodies specific for these epitopes did not show invasion inhibitory effect. These discoveries indicated that the low-complexity regions of the parasite proteins might drive immune responses away from functional domains, which may be an instructive finding for the rational design of vaccine candidates.

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Section: Introductionmentioning

confidence: 99%

Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses

Hou

Jiang

et al. 2020

Front. Immunol.

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“…Artemisinin-based chemotherapeutics have been the latest therapeutically effective options against P. falciparum, but within the last 10 years, resistance has developed in Southeast Asia and is feared to import to Africa. Hence, identification of novel target structures in the parasite is mandatory for the development of alternative anti-malaria agents (Moxon et al 2019;Narula et al 2019). Cyclic nucleotides have been appreciated as intracellular messengers not only in most animal cells but also in malaria parasites in which they control many stages of their life cycle (Baker et al 2017a(Baker et al , 2017b.…”

Section: The Role Of Cgmp For Infectious Diseasesmentioning

confidence: 99%

cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

Friebe

Sandner

Schmidtko

2019

Naunyn-Schmiedeberg's Arch Pharmacol

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Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC-and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the "9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications" held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

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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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New dimensions in the field of antimalarial research against malaria resurgence

Cited by 29 publications

References 325 publications

Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses

Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses

cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

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

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