Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Oxford University Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/109166 https://orcid.org/0000-0002-6223-6831 https://orcid.org/0000-0002-2085-7840 |
| _version_ | 1826217825098792960 |
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| author | Chandramohanadas, Rajesh Basappa, Rajesh Russell, Bruce Liew, Kingsley Yau, Yin Hoe Chong, Alvin Liu, Min Gunalan, Karthigayan Renia, Laurent Nosten, Francois Shochat, Susana Geifman Preiser, Peter Raman, Rahul Dao, Ming Suresh, Subra Sasisekharan, Ram |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Chandramohanadas, Rajesh Basappa, Rajesh Russell, Bruce Liew, Kingsley Yau, Yin Hoe Chong, Alvin Liu, Min Gunalan, Karthigayan Renia, Laurent Nosten, Francois Shochat, Susana Geifman Preiser, Peter Raman, Rahul Dao, Ming Suresh, Subra Sasisekharan, Ram |
| author_sort | Chandramohanadas, Rajesh |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:09:44Z |
| format | Article |
| id | mit-1721.1/109166 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:09:44Z |
| publishDate | 2017 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | mit-1721.1/1091662022-09-30T00:07:55Z Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species Chandramohanadas, Rajesh Basappa, Rajesh Russell, Bruce Liew, Kingsley Yau, Yin Hoe Chong, Alvin Liu, Min Gunalan, Karthigayan Renia, Laurent Nosten, Francois Shochat, Susana Geifman Preiser, Peter Raman, Rahul Dao, Ming Suresh, Subra Sasisekharan, Ram Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Sasisekharan, Ram Raman, Rahul Dao, Ming Suresh, Subra Sasisekharan, Ram 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. 2017-05-18T15:45:20Z 2017-05-18T15:45:20Z 2014-05 2014-01 Article http://purl.org/eprint/type/JournalArticle 0022-1899 1537-6613 http://hdl.handle.net/1721.1/109166 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. https://orcid.org/0000-0002-6223-6831 https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1093/infdis/jiu296 Journal of Infectious Diseases Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Oxford University Press Prof. Sasisekharan via Howard Silver |
| spellingShingle | Chandramohanadas, Rajesh Basappa, Rajesh Russell, Bruce Liew, Kingsley Yau, Yin Hoe Chong, Alvin Liu, Min Gunalan, Karthigayan Renia, Laurent Nosten, Francois Shochat, Susana Geifman Preiser, Peter Raman, Rahul Dao, Ming Suresh, Subra Sasisekharan, Ram Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species |
| title | Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species |
| title_full | Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species |
| title_fullStr | Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species |
| title_full_unstemmed | Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species |
| title_short | Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species |
| title_sort | small molecule targeting malaria merozoite surface protein 1 msp 1 prevents host invasion of divergent plasmodial species |
| url | http://hdl.handle.net/1721.1/109166 https://orcid.org/0000-0002-6223-6831 https://orcid.org/0000-0002-2085-7840 |
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