Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevents host invasion of divergent plasmodial species

TitleSmall molecule targeting malaria merozoite surface protein-1 (MSP-1) prevents host invasion of divergent plasmodial species
Publication TypeJournal Article
Year of Publication2014
AuthorsChandramohanadas, R, , , Russell, B, Liew, K, Yau, YH, Chong, A, Liu, M, Gunalan, K, Raman, R, Renia, L, Nosten, F, Shochat, SG, Dao, M, Sasisekharan, R, Suresh, S, Preiser, P
JournalJ Infect Dis
Volume210
Issue10
Pagination1616-26
Date PublishedNov 15
ISBN Number1537-6613 (Electronic)0022-1899 (Linking)
KeywordsAntimalarials/*isolation & purification/*pharmacology, chemical biology, Endocytosis/*drug effects, glycan mimetic small molecules, host invasion, Humans, Malaria, mass spectrometry, Merozoite Surface Protein 1/*antagonists & inhibitors, merozoite surface proteins, Plasmodium falciparum, Plasmodium falciparum/*drug effects, Plasmodium vivax, Plasmodium vivax/*drug effects, red blood cell
Abstract

Malaria causes nearly 1 million deaths annually. Recent emergence of multidrug resistance highlights the need to develop novel therapeutic interventions against human malaria. Given the involvement of sugar binding plasmodial proteins in host invasion, we set out to identify such proteins as targets of small glycans. Combining multidisciplinary approaches, we report the discovery of a small molecule inhibitor, NIC, capable of inhibiting host invasion through interacting with a major invasion-related protein, merozoite surface protein-1 (MSP-1). This interaction was validated through computational, biochemical, and biophysical tools. Importantly, treatment with NIC prevented host invasion by Plasmodium falciparum and Plasmodium vivax--major causative organisms of human malaria. MSP-1, an indispensable antigen critical for invasion and suitably localized in abundance on the merozoite surface represents an ideal target for antimalarial development. The ability to target merozoite invasion proteins with specific small inhibitors opens up a new avenue to target this important pathogen.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/24864124