6var

Publication Abstract from PubMed

Initiation of protein-primed (-) strand DNA synthesis in hepatitis B virus (HBV) requires interaction of the viral polymerase with a cis-acting regulatory signal, designated epsilon (epsilon), located at the 5'-end of its pre-genomic RNA (pgRNA). Binding of polymerase to epsilon is also necessary for pgRNA encapsidation. While the mechanistic basis of this interaction remains elusive, mutagenesis studies suggest its internal 6-nt "priming loop" provides an important structural contribution. epsilon might therefore be considered a promising target for small molecule interventions to complement current nucleoside-analog based anti-HBV therapies. An ideal prerequisite to any RNA-directed small molecule strategy would be a detailed structural description of this important element. Herein, we present a solution NMR structure for HBV epsilon which, in combination with molecular dynamics and docking simulations, reports on a flexible ligand "pocket", reminiscent of those observed in proteins. We also demonstrate the binding of the selective estrogen receptor modulators (SERMs) Raloxifene, Bazedoxifene, and a de novo derivative to the priming loop.Communicated by Ramaswamy H. Sarma.

Structural insights of the conserved "priming loop" of hepatitis B virus pre-genomic RNA.,LeBlanc RM, Kasprzak WK, Longhini AP, Olenginski LT, Abulwerdi F, Ginocchio S, Shields B, Nyman J, Svirydava M, Del Vecchio C, Ivanic J, Schneekloth JS Jr, Shapiro BA, Dayie TK, Le Grice SFJ J Biomol Struct Dyn. 2021 Jun 22:1-13. doi: 10.1080/07391102.2021.1934544. PMID:34155954^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.