Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species
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Small molecule with SI.pdf
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Author(s)
Chandramohanadas, Rajesh
Basappa, Rajesh
Russell, Bruce
Liew, Kingsley
Yau, Yin Hoe
Chong, Alvin
Liu, Min
Gunalan, Karthigayan
Renia, Laurent
Nosten, Francois
Date Issued
May 2014
Journal
Journal of Infectious Diseases
Publisher
Oxford University Press
Citation
Chandramohanadas, Rajesh; Basappa, Rajesh; Russell, Bruce; Liew, Kingsley; Yau, Yin Hoe; Chong, Alvin; Liu, Min et al. “Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species.” Journal of Infectious Diseases 210, no. 10 (May 2014): 1616–1626.
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Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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DOI of Published Version
https://doi.org/10.1093/infdis/jiu296
