ABSTRACT
Dengue fever is one of the major health problems in tropical and subtropical areas throughout the world. The causative agent of dengue fever is the dengue virus which is an enveloped single stranded RNA virus belongs to the family Flaviviridae and has five distinct serotypes (DENV-1, DENV-2, DENV-3, DENV-4 and DENV-5). Dengue virus is transmitted to human via bite of Aedes aegypti and Aedes albopictus mosquitoes. The clinical symptoms of dengue fever ranging from mild to severe form as dengue hemorrhagic fever and dengue shock syndrome. Pakistan is dengue endemic since 1994 but from 2006, Pakistan faced the worst condition regarding dengue in which thousands of people affected by the disease and hundreds of people lost their lives. DENV-2, DENV-3 and DENV-1 are the prevalent serotypes in Pakistan. Common diagnostic techniques are being used in Pakistan such as enzyme-linked immunosorbent assay, polymerase chain reaction and rapid diagnostic tests, while differential diagnosis, limitations of diagnostic methods and poor health care system are the real challenges in dengue diagnosis. Favorable climatic conditions, unplanned urbanization, travelling etc., are major factors responsible for dengue epidemics in Pakistan. This presentation provides update about dengue circumstances in Pakistan and also describes the way how to improve dengue situation in Pakistan.
ABSTRACT
OBJECTIVE@#To find potential peptide inhibitors against the NS2B/NS3 protease of DENV which in turn, can inhibit the viral replication inside host cell.@*METHODS@#Cyclic peptides were designed having combination of positively charged amino acids using ChemSketch software and were converted to 3D structures. DENV NS3 protein structure was retrieved from Protein Data Bank (PDB) using PDB Id: 2FOM. DENV NS3 and cylic peptides were docked using MOE software after structural optimization.@*RESULTS@#Through molecular docking it was revealed that most of the peptides bound deeply in the binding pocket of DENV NS2B/NS3 protease an had interactions with catalytic triad. Peptide 2 successfully blocked the catalytic triad of NS2B/NS3 protease. Peptide 1, 4 and 6 also had potential interactions with active residues of the NS2B/NS3 protease while all other peptides were in close contact with the active sites of NS2B/NS3 protease thus, these peptides can serve as a potential drug candidate to stop viral replication.@*CONCLUSIONS@#Thus, it can be concluded from the study that these peptides could serve as important inhibitors to inhibit the viral replication and need further in-vitro investigations to confirm their efficacy.