Title:Exploiting Dengue Virus Protease as a Therapeutic Target: Current Status, Challenges and Future Avenues
Volume: 28
Issue: 37
Author(s): Mamona Mushtaq, Sehrish Naz, Keykavous Parang and Zaheer Ul-Haq*
Affiliation:
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi,Pakistan
Keywords:
Dengue, DENV, inhibitors, peptides, peptidomimetic, protease, small molecules.
Abstract: Dengue, the oldest and the most prevalent mosquito-borne illness, is caused by the
dengue virus (DENV), from the family of Flaviviridae. It infects approximately 400 million
individuals per annum, with approximately half of the global population residing in high-risk
areas. The factors attributed to the geographic expansion of dengue, include urbanization,
population density, modern means of transportation, international travels, habit modification,
climate change, virus genetics, vector capacity, and poor vector control. Despite the significant
progress made in the past against dengue, no effective antiviral therapy is currently available.
Among the structural and non-structural proteins encoded by DENV genome, the
NS2B−NS3 protease complex is amongst the extensively studied targets for the development
of antiviral therapeutics owing to its multiple roles in virus life cycle. Furthermore, protease
inhibitors were found to be successful in Hepatitis C Virus (HCV) and Human Immunodeficiency
Virus (HIV). Likewise, several peptidic, peptide derived/peptidomimetic, and
small molecules inhibitors have been identified as DENV protease inhibitors. Unfortunately,
none of them have resulted in a clinically approved drug. Considering all the abovementioned
facts, this review descriptively explains the molecular mechanism and therapeutic
potential of DENV protease along with an up to date information on various competitive inhibitors
reported against DENV protease. This review might be helpful for the researchers
working in this area to understand the critical aspects of DENV protease that will help them
develop effective and novel inhibitors against DENV to protect lives of millions of people
worldwide.
