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Trends Parasitol. 2018 Oct;34(10):843-860. doi: 10.1016/j.pt.2018.07.011. Epub 2018 Aug 16.

Opportunities for Host-targeted Therapies for Malaria.

Author information

1
Center for Infectious Disease Research, 307 Westlake Ave N Suite 500, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Harris Hydraulics Laboratory, Box 357965, Seattle, WA 98195, USA; These authors made an equal contribution.
2
Center for Infectious Disease Research, 307 Westlake Ave N Suite 500, Seattle, WA 98109, USA; These authors made an equal contribution.
3
Center for Infectious Disease Research, 307 Westlake Ave N Suite 500, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Harris Hydraulics Laboratory, Box 357965, Seattle, WA 98195, USA.
4
Center for Infectious Disease Research, 307 Westlake Ave N Suite 500, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Harris Hydraulics Laboratory, Box 357965, Seattle, WA 98195, USA. Electronic address: alexis.kaushansky@cidresearch.org.

Abstract

Despite the recent successes of artemisinin-based antimalarial drugs, many still die from severe malaria, and eradication efforts are hindered by the limited drugs currently available to target transmissible gametocyte parasites and liver-resident dormant Plasmodium vivax hypnozoites. Host-targeted therapy is a new direction for infectious disease drug development and aims to interfere with host molecules, pathways, or networks that are required for infection or that contribute to disease. Recent advances in our understanding of host pathways involved in parasite development and pathogenic mechanisms in severe malaria could facilitate the development of host-targeted interventions against Plasmodium infection and malaria disease. This review discusses new opportunities for host-targeted therapeutics for malaria and the potential to harness drug polypharmacology to simultaneously target multiple host pathways using a single drug intervention.

KEYWORDS:

cerebral malaria; drug discovery; host–parasite interactions; liver; malaria; polyphamacology

PMID:
30122551
PMCID:
PMC6168423
DOI:
10.1016/j.pt.2018.07.011
[Indexed for MEDLINE]
Free PMC Article

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