Date Published: September 10, 2017
Author(s): Carolina de la Guardia, Mario Quijada, Ricardo Lleonart.
Dengue virus is a growing public health threat that affects hundreds of million peoples every year and leave huge economic and social damage. The virus is transmitted by mosquitoes and the incidence of the disease is increasing, among other causes, due to the geographical expansion of the vector’s range and the lack of effectiveness in public health interventions in most prevalent countries. So far, no highly effective vaccine or antiviral has been developed for this virus. Here we employed phage display technology to identify peptides able to block the DENV2. A random peptide library presented in M13 phages was screened with recombinant dengue envelope and its fragment domain III. After four rounds of panning, several binding peptides were identified, synthesized, and tested against the virus. Three peptides were able to block the infectivity of the virus while not being toxic to the target cells. Blind docking simulations were done to investigate the possible mode of binding, showing that all peptides appear to bind domain III of the protein and may be mostly stabilized by hydrophobic interactions. These results are relevant to the development of novel therapeutics against this important virus.
Dengue virus is a growing public health problem worldwide as about 390 million people get infected annually and almost 96 million people develop clinical manifestations of the disease . Other authors estimate that about 3.9 billion people from 128 countries share the risk of infection with this virus . Dengue virus can produce a wide spectrum of clinical presentations, from asymptomatic or mild manifestation to a more severe life threating manifestation, known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Severe dengue can be deadly, especially in children, due to plasma leaking, respiratory distress, edema, severe bleeding, and organ impairment .
In conclusion, we have used a novel strategy to identify inhibitors of the DENV2 infectivity and we have found three peptides out of a random peptide library, which are able to specifically bind viral envelope protein and inhibit infectivity in vitro, without showing toxicity to the cells. The binding modes suggested by blind docking simulations indicate that the interactions between these active peptides and their targets may be stabilized by hydrophobic interactions, providing information relevant to the future improvement of new antivirals against this important virus.