A short survey of dengue protease inhibitor development in the past 6 years (2015–2020) with an emphasis on similarities between DENV and SARS-CoV-2 proteases. (1st November 2021)

• Record Type: Journal Article
• Authors: Murtuja, Sheikh; Shilkar, Deepak; Sarkar, Biswatrish; Sinha, Barij Nayan; Jayaprakash, Venkatesan
• Is Part Of: Bioorganic & medicinal chemistry. Volume 49(2021)
• Publication Date: 2021-11-01
• Subjects: Dengue virus -- NS2B-NS3-pro inhibitors -- Peptidomimetics -- HTS -- High-throughput virtual screening (HTVS) -- Dengue-COVID-19 co-infection; DENV Dengue virus -- DHF Dengue hemorrhagic fever -- DSS Dengue shock syndrome -- HCV Hepatitis C Virus -- HIV Human Immuno-deficiency Virus -- HTS High-throughput screening -- HTVS High-throughput virtual screening -- JEV Japanese encephalitis virus -- NMR Nuclear magnetic resonance -- ORF Open reading frames -- SARS Severe acute respiratory syndrome-coronavirus -- SI Selectivity index -- SLC Split luciferase complementation -- WNV West Nile virus -- YFV Yellow fever virus; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116415
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Dengue remains a disease of significant concern, responsible for nearly half of all arthropod-borne disease cases across the globe. Due to the lack of potent and targeted therapeutics, palliative treatment and the adoption of preventive measures remain the only available options. Compounding the problem further, the failure of the only dengue vaccine, Dengvaxia®, also delivered a significant blow to any hopes for the treatment of dengue fever. However, the success of Human Immuno-deficiency Virus (HIV) and Hepatitis C Virus (HCV) protease inhibitors in the past have continued to encourage researchers to investigate other viral protease targets. Dengue virus (DENV) NS2B-NS3 protease is an attractive target partly due to its role in polyprotein processing and also for being the most conserved domain in the viral genome. During the early days of the COVID-19 pandemic, a few cases of Dengue-COVID 19 co-infection were reported. In this review, we compared the substrate-peptide residue preferences and the residues lining the sub-pockets of the proteases of these two viruses and analyzed the significance of this similarity. Also, we attempted to abridge the developments in anti-dengue drug discovery in the last six years (2015–2020), focusing on critical discoveries that influenced the research.