The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses

Abstract

Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin molecules, a green tea polyphenol, have shown great virucidal potential against flaviviruses, including DENV, WNV, and ZIKV. The interaction of EGCG with the viral envelope protein and viral protease, mainly identified by computational studies, describes the interaction of these molecules with viral proteins; however, how the viral NS2B/NS3 protease interacts with epigallocatechin molecules is not yet fully deciphered. Consequently, we tested the antiviral potential of two epigallocatechin molecules (EGC and EGCG) and their derivative (AcEGCG) against DENV, YFV, WNV, and ZIKV NS2B/NS3 protease. Thus, we assayed the effect of the molecules and found that a mixture of the molecules EGC (competitive) and EGCG (noncompetitive) inhibited the virus protease of YFV, WNV, and ZIKV more effectively with IC50 values of 1.17 ± 0.2 µM, 0.58 ± 0.07 µM, and 0.57 ± 0.05 µM, respectively. As these molecules fundamentally differ in their inhibitory mode and chemical structure, our finding may open a new line for developing more effective allosteric/active site inhibitors to combat flaviviruses infection.

Recent Advances on Targeting Proteases for Antiviral Development

“…Green tea ( Camellia sinensis ) is regarded as the second most popular drink in the world and is extensively researched, and used, for its pharmacologically active components, including anti-inflammatory properties, and remedial effects for diabetes, Alzheimer’s disease, oral cancer and dermatitis [ 158 ]. Recently, Coronado et al identified that epigallocatechin 46 and epigallocatechin gallate 47 , natural occurring polyphenols present in green tea, and their derivative EGCG octaacetate 48 ( Figure 19 ) are able to inhibit flaviviruse proteases within the sub-micromolar range [ 159 ]. Surprisingly, although all compounds share a common scaffold, they have exhibited different binding modes with 46 exhibiting a competitive inhibition behavior, while 47 and 48 are non-competitive inhibitors, possibly acting on an allosteric site.…”