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

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

  • J Infect Dis. 2014 Nov 15;210(10):1616-26. doi: 10.1093/infdis/jiu296.
Rajesh Chandramohanadas 1,  Basappa 2,  Bruce Russell 3,  Kingsley Liew 2,  Yin Hoe Yau 4,  Alvin Chong 2,  Min Liu 2,  Karthigayan Gunalan 4,  Rahul Raman 5,  Laurent Renia 6,  Francois Nosten 7,  Susana Geifman Shochat 4,  Ming Dao 8,  Ram Sasisekharan 9,  Subra Suresh 10,  Peter Preiser 11
Affiliations

Affiliations

  • 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.
PMID: 24864124 DOI: 10.1093/infdis/jiu296
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-124078
    Host Invasion Inhibitor