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

Publication date: Available online 29 August 2019Source: Antiviral ResearchAuthor(s): Antonello Pessi, Sandra L. Bixler, Veronica Soloveva, Sheli Radoshitzky, Cary Retterer, Tara Kenny, Rouzbeh Zamani, Glenn Gomba, Dima Gharabeih, Jay Wells, Kelly S. Wetzel, Travis K. Warren, Ginger Donnelly, Sean A. Van Tongeren, Jesse Steffens, Allen J. Duplantier, Christopher D. Kane, Pascale Vicat, Valerie Couturier, Kent E. KesterAbstractThe 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 peptides were in low mic...
Source: Antiviral Therapy - Category: Virology Source Type: research