Peptide-derivatized dendrimers inhibit human cytomegalovirus infection by blocking virus binding to cell surface heparan sulfate

Abstract

Dendrimers are hyperbranched synthetic well-defined molecules with a number of potential applications, especially in relation to the need for new antiviral agents. One subclass of dendrimers are peptide derivatized-dendrimers which consist of a peptidyl branching core and covalently attached surface peptide functional units. Few studies have addressed the potential uses of peptide dendrimers as direct-acting antiviral agents. Here, we report on the ability of two peptide dendrimers, SB105 and SB105_A10, to directly and almost completely inhibit human cytomegalovirus (HCMV) replication in both primary fibroblasts and endothelial cells; the agents were also found to inhibit murine CMV replication, whereas they were not able to inhibit the adenovirus or vesicular stomatitis virus. The peptide dendrimers prevented adsorption of the HCMV to cells at 4° C, whereas SB104, a dendrimer with a different amino acid sequence within the functional group and minimal anticytomegaloviral activity, was ineffective in blocking HCMV attachment. In effect, SB105_A10 bound to human cells through an interaction with cell surface heparan sulfate and thereby blocked virion attachment to target cells. These results indicate that the SB105 and SB105_A10 dendrimers could provide a useful starting point for the development of novel molecules to block HCMV infection.

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

“…In view of this, the peptides derived from the natural COOH-terminal sequences of CXCL9 and CXCL12γ might be lead molecules for the generation of antiviral drugs that block the entry of viruses such as HSV-1, RSV and DENV-2 by binding to GAGs on target cells. The potency of these antiviral peptides may be increased by alternative formulations, as demonstrated for peptide-derived dendrimers [75][76][77][78]. As it is known that other viruses such as herpesviruses (e.g.…”

The US16 Gene of Human Cytomegalovirus Is Required for Efficient Viral Infection of Endothelial and Epithelial Cells

“…Adsorption of radiolabeled HCMV virions was performed as previously described (24). In brief, prechilled HMVEC monolayers were infected with equivalent amounts of precooled [ 3 H]thymidine-labeled RVTRwt or RVUS16stop virions (normalized to equivalent genome copy numbers by real-time PCR).…”

Activity of the antimicrobial peptide P34 against bovine alphaherpesvirus type 1

“…After a washing step to remove non-adsorbed viral particles, cells were incubated or not with the nontoxic concentration of P34, as previously described by LUGANINI et al (2010). After incubation for 24 and 48h, microplates were frozen, thawed, and the supernatant submitted to virus titration.…”