4.5 Review

A Critical Observation on the Design and Development of Reported Peptide Inhibitors of DENV NS2B-NS3 Protease in the Last Two Decades

Journal

MINI-REVIEWS IN MEDICINAL CHEMISTRY
Volume 22, Issue 8, Pages 1108-1130

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389557521666211101154619

Keywords

Peptide; dengue; flavivirus; NS2B-NS3; DENV2; protease inhibitors; cyclic peptides

Funding

  1. DSTSERB, Govt. of India [EMR/2016/005711/]

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This article provides a detailed analysis of each case of design and development of peptide inhibitors against DENV NS2B-NS3 protease in the past two decades. The reasons for their inhibitory activity are discussed, and suggestions to improve the inhibitory activity are highlighted whenever possible.
Dengue is one of the neglected tropical diseases, which remains a reason for concern as cases seem to rise every year. The failure of the only dengue vaccine, Dengvaxia (R), has made the problem more severe and humanity has no immediate respite from this global burden. Dengue virus (DENV) NS2B-NS3 protease is an attractive target partly due to its role in polyprotein processing. Also, since it is among the most conserved domains in the viral genome, it could produce a broad scope of opportunities toward antiviral drug discovery in general. This review has made a detailed analysis of each case of the design and development of peptide inhibitors against DENV NS2B-NS3 protease in the last two decades. Also, we have discussed the reasons attributed to their inhibitory activity, and wherever possible, we have highlighted the concerns raised, challenges met, and suggestions to improve the inhibitory activity. Thus, we attempt to take the readers through the designing and development of reported peptide inhibitors and gain insight from these developments, which could further contribute toward strategizing the designing and development of peptide inhibitors of DENV protease with improved properties in the coming future.

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