Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication.
Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strat...
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doaj-22b7a6d83b9b4f08b16712fc9cbdeaae2020-11-24T21:37:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9456110.1371/journal.pone.0094561Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication.Hussin A RothanHirbod BahraniZulqarnain MohamedNoorsaadah Abd RahmanRohana YusofDengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5±0.1 μM. The real-time proliferation assay (RTCA) and the end-point proliferation assay (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.http://europepmc.org/articles/PMC3983197?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hussin A Rothan Hirbod Bahrani Zulqarnain Mohamed Noorsaadah Abd Rahman Rohana Yusof |
spellingShingle |
Hussin A Rothan Hirbod Bahrani Zulqarnain Mohamed Noorsaadah Abd Rahman Rohana Yusof Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication. PLoS ONE |
author_facet |
Hussin A Rothan Hirbod Bahrani Zulqarnain Mohamed Noorsaadah Abd Rahman Rohana Yusof |
author_sort |
Hussin A Rothan |
title |
Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication. |
title_short |
Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication. |
title_full |
Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication. |
title_fullStr |
Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication. |
title_full_unstemmed |
Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication. |
title_sort |
fusion of protegrin-1 and plectasin to map30 shows significant inhibition activity against dengue virus replication. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5±0.1 μM. The real-time proliferation assay (RTCA) and the end-point proliferation assay (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities. |
url |
http://europepmc.org/articles/PMC3983197?pdf=render |
work_keys_str_mv |
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