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Title: Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species
Authors: Chandramohanadas, Rajesh
Russell, B.
Liew, K.
Yau, Y. H.
Chong, A.
Min, L.
Gunalan, K.
Raman, R.
Renia, L.
Nosten, F.
Shochat, S. G.
Dao, M.
Sasisekharan, R.
Suresh, S.
Preiser, P.
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2014
Source: Chandramohanadas, R., Basappa , Russell, B., Liew, K., Yau, Y. H., Chong, A., Min, L., Gunalan, K., Raman, R., Renia, L., Nosten, F., Shochat, S. G., Dao, M., Sasisekharan, R., Suresh, S., & Preiser, P. (2014). Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevent Host Invasion of Divergent Plasmodial Species. Journal of Infectious Diseases, in press.
Series/Report no.: Journal of infectious diseases
Abstract: Malaria causes nearly 1 million deaths annually. Recent emergence of multi-drug 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 multi-disciplinary 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.
DOI: 10.1093/infdis/jiu296
Rights: © 2014 The Author. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Infectious Diseases, Oxford University Press. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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