Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

Abstract

Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

Surface chemistry of gold nanoparticles for health-related applications

“…In addition to cancer treatments, AuNPbased/assisted therapy can be applied to cardiovascular diseases, intestinal microora and infection. [144][145][146] Bacterial infection especially caused by antibiotic-resistant bacteria is becoming a more serious threat to the human health. Small molecule-modied AuNPs showing excellent antibacterial activity can serve as attractive alternatives to conventional antibiotics.…”

Virucidal Activity of Gold Nanoparticles Synthesized by Green Chemistry Using Garlic Extract

“…Low cytotoxicity is one of the most important requirements for any potential antiviral agent; Fatima et al described the non-toxicity (CC 50 > 500 µg/mL) of synthesized green nanoparticles and their precursors tested in the same way by the MTT assay on Vero cells [20]. Cagno et al also reported the lack of significant toxicity at similar concentrations (CC 50 ≥ 100-300 µg/mL) of gold NPs coated with undecanesulfonic acid (MUS)-containing ligands and their pre-MUS ligand [21].…”

Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation

“…11-mercaptoundecane sulfonate sodium salt (MUS) was synthesized according to a previously reported protocol. [20] All solvents were ACS grade and used without further purification.…”