Cholesterol-conjugated stapled peptides inhibit Ebola and Marburg viruses in vitro and in vivo.

Cholesterol-conjugated stapled peptides inhibit Ebola and Marburg viruses in vitro and in vivo. Antiviral Res. 2019 Aug 29;:104592 Authors: Pessi A, Bixler SL, Soloveva V, Radoshitzky S, Retterer C, Kenny T, Zamani R, Gomba G, Gharabeih D, Wells J, Wetzel KS, Warren TK, Donnelly G, Van Tongeren SA, Steffens J, Duplantier AJ, Kane CD, Vicat P, Couturier V, Kester KE, Shiver J, Carter K, Bavari S Abstract The Filoviridae family consists of five ebolavirus species, Ebola (EBOV), Sudan (SUDV), Bundibugyo virus (BDBV), Reston (RESTV), and Taï Forest (TAFV) viruses, and a Marburgvirus species, with Marburg (MARV) and Ravn (RAVV) viruses. Ebola virus (EBOV) has emerged as a significant public health concern since the 2013-2016 Ebola Virus Disease outbreak in Western Africa. Currently, there are no therapeutics approved and the need for Ebola-specific therapeutics remains a gap. In search for anti-Ebola therapies we tested the idea of using inhibitory properties of peptides corresponding to the C-terminal heptad-repeat (HR2) domains of class I fusion proteins against EBOV infection. The fusion protein GP2 of EBOV belongs to class I, suggesting that a similar strategy to HIV may be applied to inhibit EBOV infection. The serum half-life of peptides was expanded by cholesterol conjugation to allow daily dosing. The peptides were further constrained to stabilize a helical structure to increase the potency of inhibition. The EC50s of lead peptid...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research