Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice
Aims: Enterovirus A71 (EV-A71) is an etiological agent of hand foot and mouth disease (HFMD) and has the potential to cause severe neurological infections in children. L-SP40 peptide was previously known to inhibit EV-A71 by prophylactic action. This study aimed to identify the mechanism of inhibiti...
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| Format: | Article |
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Elsevier
2021
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| Online Access: | http://eprints.sunway.edu.my/1880/ |
| _version_ | 1848802154065690624 |
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| author | Lalani, Salima Tan, Soon Hao Tan, Kuan Onn * Lim, Hui Xuan * Ong, Kien Chai Wong, Kum Thong Poh, Chit Laa * |
| author_facet | Lalani, Salima Tan, Soon Hao Tan, Kuan Onn * Lim, Hui Xuan * Ong, Kien Chai Wong, Kum Thong Poh, Chit Laa * |
| author_sort | Lalani, Salima |
| building | SU Institutional Repository |
| collection | Online Access |
| description | Aims: Enterovirus A71 (EV-A71) is an etiological agent of hand foot and mouth disease (HFMD) and has the potential to cause severe neurological infections in children. L-SP40 peptide was previously known to inhibit EV-A71 by prophylactic action. This study aimed to identify the mechanism of inhibition in Rhabdomyosarcoma (RD) cells and in vivo therapeutic potential of L-SP40 peptide in a murine model.
Main methods: A pull-down assay was performed to identify the binding partner of the L-SP40 peptide. Co-immunoprecipitation and co-localization assays with the L-SP40 peptide were employed to confirm the receptor partner in RD cells. The outcomes were validated using receptor knockdown and antibody blocking assays. The L-SP40 peptide was further evaluated for the protection of neonatal mice against lethal challenge by mouse-adapted EV-A71.
Key findings: The L-SP40 peptide was found to interact and co-localize with nucleolin, the key attachment receptor of Enteroviruses A species, as demonstrated in the pull-down, co-immunoprecipitation and co-localization assays. Knockdown of nucleolin from RD cells led to a significant reduction of 3.5 logs of viral titer of EV-A71. The L-SP40 peptide demonstrated 80% protection of neonatal mice against lethal challenge by the mouse-adapted virus with a drastic reduction in the viral loads in the blood (~4.5 logs), skeletal muscles (1.5 logs) and brain stem (1.5 logs).
Significance: L-SP40 peptide prevented severe hind limb paralysis and death in suckling mice and could serve as a potential broad-spectrum antiviral candidate to be further evaluated for safety and potency in future clinical trials against EV-A71 |
| first_indexed | 2025-11-14T21:18:50Z |
| format | Article |
| id | sunway-1880 |
| institution | Sunway University |
| institution_category | Local University |
| last_indexed | 2025-11-14T21:18:50Z |
| publishDate | 2021 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | sunway-18802021-12-06T02:42:51Z http://eprints.sunway.edu.my/1880/ Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice Lalani, Salima Tan, Soon Hao Tan, Kuan Onn * Lim, Hui Xuan * Ong, Kien Chai Wong, Kum Thong Poh, Chit Laa * QR355 Virology Aims: Enterovirus A71 (EV-A71) is an etiological agent of hand foot and mouth disease (HFMD) and has the potential to cause severe neurological infections in children. L-SP40 peptide was previously known to inhibit EV-A71 by prophylactic action. This study aimed to identify the mechanism of inhibition in Rhabdomyosarcoma (RD) cells and in vivo therapeutic potential of L-SP40 peptide in a murine model. Main methods: A pull-down assay was performed to identify the binding partner of the L-SP40 peptide. Co-immunoprecipitation and co-localization assays with the L-SP40 peptide were employed to confirm the receptor partner in RD cells. The outcomes were validated using receptor knockdown and antibody blocking assays. The L-SP40 peptide was further evaluated for the protection of neonatal mice against lethal challenge by mouse-adapted EV-A71. Key findings: The L-SP40 peptide was found to interact and co-localize with nucleolin, the key attachment receptor of Enteroviruses A species, as demonstrated in the pull-down, co-immunoprecipitation and co-localization assays. Knockdown of nucleolin from RD cells led to a significant reduction of 3.5 logs of viral titer of EV-A71. The L-SP40 peptide demonstrated 80% protection of neonatal mice against lethal challenge by the mouse-adapted virus with a drastic reduction in the viral loads in the blood (~4.5 logs), skeletal muscles (1.5 logs) and brain stem (1.5 logs). Significance: L-SP40 peptide prevented severe hind limb paralysis and death in suckling mice and could serve as a potential broad-spectrum antiviral candidate to be further evaluated for safety and potency in future clinical trials against EV-A71 Elsevier 2021-12 Article PeerReviewed Lalani, Salima and Tan, Soon Hao and Tan, Kuan Onn * and Lim, Hui Xuan * and Ong, Kien Chai and Wong, Kum Thong and Poh, Chit Laa * (2021) Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice. Life Sciences, 287. p. 120097. ISSN 0024-3205 http://doi.org/10.1016/j.lfs.2021.120097 doi:10.1016/j.lfs.2021.120097 |
| spellingShingle | QR355 Virology Lalani, Salima Tan, Soon Hao Tan, Kuan Onn * Lim, Hui Xuan * Ong, Kien Chai Wong, Kum Thong Poh, Chit Laa * Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice |
| title | Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice |
| title_full | Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice |
| title_fullStr | Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice |
| title_full_unstemmed | Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice |
| title_short | Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice |
| title_sort | molecular mechanism of l-sp40 peptide and in vivo efficacy against ev-a71 in neonatal mice |
| topic | QR355 Virology |
| url | http://eprints.sunway.edu.my/1880/ http://eprints.sunway.edu.my/1880/ http://eprints.sunway.edu.my/1880/ |