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Graphical abstract Highlights • Three peptides derived from envelope glycoprotein were evaluated for inhibiting the viral infection. • Pep2 showed highest percentage of inhibitory activity towards, DENV-1, DENV-2, DENV-3 and DENV-4. • The synthetic peptides inhibited viral entry by binding to the envelope glycoprotein of Dengue Virus. Abstract 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 IC 50 in the range of 10–33 μM. Pep1 was found effective against DENV-2, DENV-3, and DENV-4 (IC 80 below 50 μM). Pep2 showed the highest inhibitory activity against all four serotypes (IC 50 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. [ABSTRACT FROM AUTHOR]

Highlights: [•] Severe cases are often observed in patients of 2nd infection with dengue virus. [•] ADE is the hypothesis to explain the mechanism for severe cases 2nd infection. [•] Human monoclonal antibodies to neutralize 1–4 serotypes were prepared. [•] No difference was observed in ADE activities between antibodies from DF and DHF. [Copyright &y& Elsevier]