Format

Send to

Choose Destination
See comment in PubMed Commons below
J Infect Dis. 2014 Nov 15;210(10):1616-26. doi: 10.1093/infdis/jiu296. Epub 2014 May 26.

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

Author information

1
Interdisciplinary Research Group of Infectious Diseases, Singapore MIT Alliance for Research and Technology Centre (SMART) Singapore University of Technology and Design, 20 Dover Drive.
2
Interdisciplinary Research Group of Infectious Diseases, Singapore MIT Alliance for Research and Technology Centre (SMART).
3
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore and.
4
School of Biological Sciences, Nanyang Technological University, Singapore.
5
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
6
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR).
7
Shoklo Malaria Research Unit, Mae Sot, Thailand Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom.
8
Interdisciplinary Research Group of Infectious Diseases, Singapore MIT Alliance for Research and Technology Centre (SMART) Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge;
9
Interdisciplinary Research Group of Infectious Diseases, Singapore MIT Alliance for Research and Technology Centre (SMART) Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
10
Department of Biomedical Engineering and Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh.
11
Interdisciplinary Research Group of Infectious Diseases, Singapore MIT Alliance for Research and Technology Centre (SMART) School of Biological Sciences, Nanyang Technological University, Singapore.

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.

KEYWORDS:

Plasmodium falciparum; Plasmodium vivax; chemical biology; glycan mimetic small molecules; host invasion; malaria; mass spectrometry; merozoite surface proteins; red blood cell

PMID:
24864124
PMCID:
PMC4334792
DOI:
10.1093/infdis/jiu296
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Support Center