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Title: Small molecule targeting malaria Merozoite surface protein-1 (MSP-1) prevents host invasion of divergent Plasmodial species
Authors: Chandramohanadas R.
Russell B. 
Liew K. 
Yau Y.H.
Chong A. 
Liu M. 
Gunalan K.
Raman R.
Renia L. 
Nosten F.
Shochat S.G.
Dao M.
Sasisekharan R.
Suresh S. 
Preiser P.
Keywords: 2 butyl 5 chloro 3 (4 nitro benzyl) 3h imidazole 4 carbaldehyde
merozoite surface protein 1
unclassified drug
antimalarial agent
merozoite surface protein 1
binding affinity
carboxy terminal sequence
computer model
controlled study
in vitro study
molecular docking
parasite phenomena and functions
Plasmodium falciparum
Plasmodium vivax
protein analysis
protein binding
protein localization
protein protein interaction
sequence alignment
species invasion
surface plasmon resonance
antagonists and inhibitors
drug effects
isolation and purification
Plasmodium falciparum
Plasmodium vivax
Merozoite Surface Protein 1
Plasmodium falciparum
Plasmodium vivax
Issue Date: 2014
Publisher: Oxford University Press
Citation: Chandramohanadas R., Russell B., Liew K., Yau Y.H., Chong A., Liu M., 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) prevents host invasion of divergent Plasmodial species. Journal of Infectious Diseases 210 (10) : 1616-1626. ScholarBank@NUS Repository.
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. © 2014 © The Author 2014.
Source Title: Journal of Infectious Diseases
ISSN: 0022-1899
DOI: 10.1093/infdis/jiu296
Appears in Collections:Staff Publications

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