In vitro analysis of synthetic peptides in blocking the entry of dengue virus
| Autor: | Akanitt Jittmittraphap, A. Alwin Prem Anand, Pornsawan Leaungwutiwong, Siriporn Chattanadee, R. Shenbagarathai, Asnet Mary John |
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| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
medicine.drug_class viruses Peptide Microbial Sensitivity Tests Dengue virus medicine.disease_cause Antiviral Agents Virus Cell Line Dengue fever Inhibitory Concentration 50 03 medical and health sciences Viral entry Virology Chlorocebus aethiops medicine Animals 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology 030306 microbiology Dengue Virus Virus Internalization medicine.disease biology.organism_classification Macaca mulatta Flavivirus Infectious Diseases chemistry Viral disease Antiviral drug Oligopeptides |
| Zdroj: | Virus Research. 260:142-150 |
| ISSN: | 0168-1702 |
| Popis: | Dengue fever is the most prevalent arthropod-borne viral disease, and no specific therapeutic or promising antiviral drug is available for its treatment. Peptide inhibitors are less toxic than synthetic compounds and have found proven effective against viral infections. Here, three peptides that mimic part of the E protein of the dengue virus (DENV) were synthesized and evaluated for their inhibitory activity against four serotypes of DENV in African green monkey kidney (Vero) and rhesus macaque (Macaca mulatta) monkey kidney (LLC-MK2) cell lines. The three peptides, Pep1, Pep2, and Pep3 are located in domains I, II, and III of the E protein respectively. All three peptides effectively reduced >80% of focus forming units in the virus treated mammalian cell lines than control and exhibited their IC50 in the range of 10–33 μM. Pep1 was found effective against DENV-2, DENV-3, and DENV-4 (IC80 below 50 μM). Pep2 showed the highest inhibitory activity against all four serotypes (IC50 below 20 μM). Pep3 reduced the 80% focus forming units in all serotypes at the concentration of 40 μM. Evaluation of peptides at different time points of viral infection in the mammalian cell lines revealed that the peptides inhibited viral infection by binding to the virus and not by binding to cellular receptors and blocking viral entry. The peptides assumedly exert their inhibitory effects by binding to the E protein and repressing its conformational changes; this prevents the virus from binding to cellular receptors, thereby inhibiting viral entry. Hence, these peptides might limit viral spread and reduce the virus’s ability to infect. |
| Databáze: | OpenAIRE |
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