Abstract
BackgroundAlthough there have been considerable advances in the study of dengue virus, no vaccines or anti-dengue drugs are currently available for humans. Therefore, new approaches are necessary for the development of potent anti-dengue drugs. Natural antimicrobial peptides (AMPs) with potent antiviral activities are potential hits-to-leads for antiviral drug discovery. We performed this study to identify and characterise the inhibitory potential of the latarcin peptide (Ltc 1, SMWSGMWRRKLKKLRNALKKKLKGE) against dengue virus replication in infected cells.ResultsThe Ltc 1 peptide showed a significantly inhibitory effect against the dengue protease NS2B-NS3pro at 37°C, a physiological human temperature, (IC50, 12.68 ± 3.2 μM), and greater inhibitory effect was observed at 40°C, a temperature similar to a high fever (IC50, 6.58 ± 4.1 μM). A greater reduction in viral load (p.f.u./ml) was observed at simultaneous (0.7 ± 0.3 vs. 7.2 ± 0.5 control) and post-treatment (1.8 ± 0.7 vs. 6.8 ± 0.6 control) compared to the pre-treatment (4.5 ± 0.6 vs. 6.9 ± 0.5 control). Treatment with the Ltc 1 peptide reduced the viral RNA in a dose-dependent manner with EC50 values of 8.3 ± 1.2, 7.6 ± 2.7 and 6.8 ± 2.5 μM at 24, 48 and 72 h, respectively.ConclusionsThe Ltc 1 peptide exhibited significant inhibitory effects against dengue NS2B-NS3pro and virus replication in the infected cells. Therefore, further investigation is necessary to develop the Ltc 1 peptide as a new anti-dengue therapeutic.
Highlights
There have been considerable advances in the study of dengue virus, no vaccines or anti-dengue drugs are currently available for humans
This study demonstrates for the first time significant inhibition by Ltc 1 against dengue NS2B-NS3pro and dengue virus replication in HepG2 cells
The inhibitory potential of the Ltc 1 peptide against the Dengue virus serotype-2 (DENV2) protease NS2B-NS3pro The results of the global rigid complementary docking showed that the Ltc 1 peptide bound the dengue NS2BNS3pro near the active site (Figure 1A and 1B)
Summary
There have been considerable advances in the study of dengue virus, no vaccines or anti-dengue drugs are currently available for humans. New approaches are necessary for the development of potent anti-dengue drugs. We performed this study to identify and characterise the inhibitory potential of the latarcin peptide (Ltc 1, SMWSGMWRRKLKKLRNALKKKLKGE) against dengue virus replication in infected cells. Over 390 million people are infected with dengue virus (DENV) annually in over 100 counties, resulting in approximately 12000 deaths [3]. In addition to the global health problem caused by dengue infection, it has an DENV is an enveloped virus with a positive stranded RNA genome of approximately 11 kb in length that encodes a single polypeptide. The viral NS2B-NS3pro is a potential target for the design and development of antiviral drugs [10,11]. NS2B-NS3pro consists of 185 residues from the N-terminal of the NS3 protein and the central 44 residues of the hydrophilic domain of NS2B [12,13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
