Therapeutics through glycobiology: an approach for targeted elimination of malaria.

The emergence of drug resistance in Plasmodium jeopardises worldwide malaria eradication efforts necessitating novel therapeutic approaches and therefore the identification of key metabolic pathways of parasite and human host for drug development garners importance. Enzymopathies like glucose-6-phosphate-dehydrogenase (G6PD) and pyruvate kinase (PK) deficiencies have been shown to protect against the severe consequences of malaria. Glycome profiles and the regulatory mechanisms involving the microRNAs or transcription factors' expression related to the histo-blood group glycogenes may add up to resolve the underlying pathogenesis. The glycan derivatives viz. heparin-like molecules (HLMs) interrupt parasite proliferation that can be exploited as leads for alternative therapies. The Plasmodium invasion of erythrocytes involve events of receptor recognition, adhesion, and ligand interactions. Since post translational modifications like N-glycosylation of merozoite surface proteins and several erythrocyte cluster of differentiation (CD) antigens and complement receptor, among others, are crucial to parasite invasion, understanding of post translational modification of proteins involved in the parasite-host interactions should identify viable antimalarial strategies.

Transcriptomic approaches for identifying potential transmission blocking vaccine candidates in Plasmodium falciparum: a review of current knowledge and future directions.

Utilizing transcriptomics, promising methods for identifying unique genes associated with Plasmodium gametocyte development offer a potential avenue for novel candidate targets in transmission blocking vaccine development. In this review, we identified 40 publicly available transcriptomic datasets related to parasite factors linked with sexual stage transmission, from which we analyzed two RNA-Seq datasets to identify potential genes crucial for the transmission of P. falciparum from humans to mosquito vectors. Differential expression analysis revealed 3500 (2489 upregulated and 1011 downregulated) common genes differentially expressed throughout sexual stage development of P. falciparum occurring in both humans (gametocyte stage II, V) and mosquitoes (ookinete). Among which 1283 (914 upregulated and 369 downregulated) and 826 (719 upregulated and 107 downregulated) genes were specific to female and male gametocytes, respectively. Also, 830 potential transition associated genes were identified that may be involved in the adaptation and survival of the parasite in between human and mosquito stages. Additionally, we reviewed the functional aspects of important genes highly expressed throughout the sexual stage pathway and evaluated their suitability as vaccine candidates. The review provides researchers with insight into the importance of publicly available transcriptomic datasets for identifying critical and novel gametocyte markers that may aid in the development of rational transmission blocking strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03752-3.