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. ISSN 0024-3205, DOI https://doi.org/10.1016/j.lfs.2021.120097.
Full text not available from this repository.Abstract
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 EVA71 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. Coimmunoprecipitation 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 mouseadapted 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 mouseadapted virus with a drastic reduction in the viral loads in the blood (similar to 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.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education, Malaysia under FRGS [FRGS/1/2018/SKK11/SYUC/03/3], [FRGS/1/2020/SKK06/SYUC/01/1], Centre for Virus and Vaccine Research, Sunway University |
| Uncontrolled Keywords: | Enterovirus A71 (EV-A71); Hand foot and mouth disease (HFMD); Antiviral; In vivo protection; Nucleolin; L-SP40 peptide |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Pathology Department |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 16 Aug 2022 08:18 |
| Last Modified: | 16 Aug 2022 08:18 |
| URI: | http://eprints.um.edu.my/id/eprint/28662 |
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