title: A perspective on targeting non-structural proteins to combat neglected tropical diseases: Dengue, West Nile and Chikungunya viruses.
abstract: Neglected tropical diseases are major causes of fatality in poverty stricken regions across Africa, Asia and some part of America. The combined potential health risk associated with arthropod-borne viruses (arboviruses); Dengue virus (DENV), West Nile Virus (WNV) and Chikungunya Virus (CHIKV) is immense. These arboviruses are either emerging or re-emerging in many regions with recent documented outbreaks in the United States. Despite several recent evidences of emergence, currently there are no approved drugs or vaccines available to counter these diseases. Non-structural proteins encoded by these RNA viruses are essential for their replication and maturation and thus may offer ideal targets for developing antiviral drugs. In recent years, several protease inhibitors have been sourced from plant extract, synthesis, computer aided drug design and high throughput screening as well as through drug reposition based approaches to target the non-structural proteins. The protease inhibitors have shown different levels of inhibition and may thus provide template to develop selective and potent drugs against these devastating arboviruses. This review seeks to shed light on the design and development of antiviral drugs against DENV, WNV and CHIKV to date. To the best of our knowledge, this review provides the first comprehensive update on the development of protease inhibitors targeting non-structural proteins of three most devastating arboviruses, DENV, WNV and CHIKV.
authors.affiliation: School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa.
authors.forename: Soumendranath
authors.initials: S
authors.lastname: Bhakat
authors.affiliation: School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa.
authors.forename: Wilson
authors.initials: W
authors.lastname: Karubiu
authors.affiliation: Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
authors.affiliation: School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa. Electronic address: soliman@ukzn.ac.za.
authors.forename: Mahmoud E S
authors.initials: ME
authors.lastname: Soliman
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D065632:Chikungunya Fever / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D002646:Chikungunya virus / Q000378:metabolism; D003715:Dengue / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D003716:Dengue Virus / Q000378:metabolism; D011487:Protein Conformation; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D014765:Viral Vaccines / Q000627:therapeutic use; D014901:West Nile Fever / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D014902:West Nile virus / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines
keywords: Chikungunya virus; Dengue virus; Non-structural proteins; Protease inhibitors; West Nile virus