Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species
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 target...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2014
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| Online Access: | https://hdl.handle.net/10356/96464 http://hdl.handle.net/10220/19458 |
| _version_ | 1811683411334529024 |
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| author | Chandramohanadas, Rajesh Russell, B. Basappa 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. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Chandramohanadas, Rajesh Russell, B. Basappa 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. |
| author_sort | Chandramohanadas, Rajesh |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T04:12:18Z |
| format | Journal Article |
| id | ntu-10356/96464 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:12:18Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/964642023-02-28T17:04:20Z Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species Chandramohanadas, Rajesh Russell, B. Basappa 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. School of Biological Sciences DRNTU::Science::Biological sciences 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. Accepted version 2014-05-28T02:34:33Z 2019-12-06T19:31:08Z 2014-05-28T02:34:33Z 2019-12-06T19:31:08Z 2014 2014 Journal Article 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. https://hdl.handle.net/10356/96464 http://hdl.handle.net/10220/19458 10.1093/infdis/jiu296 24864124 en Journal of infectious diseases © 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: [http://dx.doi.org/10.1093/infdis/jiu296]. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Chandramohanadas, Rajesh Russell, B. Basappa 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. Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species |
| title | Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species |
| title_full | Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species |
| title_fullStr | Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species |
| title_full_unstemmed | Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species |
| title_short | Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevent host invasion of divergent plasmodial species |
| title_sort | small molecule targeting malaria merozoite surface protein 1 msp 1 prevent host invasion of divergent plasmodial species |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/96464 http://hdl.handle.net/10220/19458 |
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