Heparan sulfate proteoglycans (HSPG) are composed of unbranched, negatively charged heparan sulfate (HS) polysaccharides attached to a variety of cell surface or extracellular matrix proteins. Widely expressed, they mediate many biological activities, including angiogenesis, blood coagulation, developmental processes, and cell homeostasis. HSPG are highly sulfated and broadly used by a range of pathogens, especially viruses, to attach to the cell surface. In this review, we summarize the current knowledge on HSPG–virus interactions and distinguish viruses with established HS binding, viruses that bind HS only after intra-host or cell culture adaptation, and finally, viruses whose dependence on HS for infection is debated. We also provide an overview of the antiviral compounds designed to interfere with HS binding. Many questions remain about the true importance of these receptors in vivo, knowledge that is critical for the design of future antiviral therapies.

Sulfonated cyclodextrins show nontoxic, broad-spectrum virucidal activity in vitro, ex vivo, and in vivo.

Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10⁻⁸–10⁻⁶ M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10⁻⁷–10⁻⁴ M) increase the half-life of a green fluorescent protein expressing adenovirus from ∼48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of magnitude lower concentrations. PEG and sucrose maintained immunogenicity in vivo for viruses stored for 10 days at 37 °C. To achieve rational design of viral-vaccine stabilizers, our approach is aided by simplified quantitative models based on a single rate-limiting step.

Recent studies reported a broad but selective antiviral activity of 25-hydroxycholesterol (25HC) against enveloped viruses, being apparently inactive against non-enveloped viruses. Here we show that 25HC is endowed with a marked antiviral activity against three pathogenic non-enveloped viruses, i.e. human papillomavirus-16 (HPV-16), human rotavirus (HRoV) and human rhinovirus (HRhV), thus significantly expanding its broad antiviral spectrum, so far recognized to be limited to viruses with envelope. Moreover, here we disclose the remarkable antiviral activity of another oxysterol of physiological origin, i.e. 27-hydroxycholesterol (27HC), against HPV-16, HRoV and HRhV. We have also identified a much weaker antiviral activity of other oxysterols of pathophysiological relevance, i.e 7α-hydroxycholesterol, 7β-hydroxycholesterol and 7-ketocholesterol. These findings suggest that appropriate modulation of endogenous production of oxysterols might be a primary host strategy to counteract a broad panel of viral infections. Moreover, 25HC and 27HC could be considered for new therapeutic strategies against HPV-16, HRoV and HRhV.