Sulfonated Nanomaterials with Broad-Spectrum Antiviral Activity Extending beyond Heparan Sulfate-Dependent Viruses

Abstract

Viral infections are among the main causes of death worldwide and we lack antivirals for the majority of viruses. Heparin-like sulfated or sulfonated compounds have been known for decades for their ability to prevent the infection of heparan sulfate proteoglycans (HSPG) dependent viruses, even though only in a reversible way. We have previously shown that gold nanoparticles and β-cyclodextrins coated with mercapto-undecane sulfonic acid (MUS) inhibit HSPG-dependent viruses irreversibly, while retaining the low-toxicity profile of most heparin-like compounds. In this work we show that, in stark contrast with heparin, these compounds also inhibit different strains of influenza virus and vesicular stomatitis virus (VSV), which do not bind HSPG. The antiviral action is virucidal and irreversible for influenza A virus (H1N1), while for VSV there is a reversible inhibition of viral attachment to the cell. These results further broaden the spectrum of activity of MUS-coated gold nanoparticles and β-cyclodextrins.

SARS-CoV-2 Inhibition by Sulfonated Compounds

“…This mechanism may then not be applicable to CoVs due to the distance between the RBD and the envelope. Alternatively, and as previously described for VSV [32], the absence of virucidal activity of MUS:OT NP and MUS CD could be due to the poor affinity of the SARS-CoV-2 spike protein for HS. This second scenario is supported by the absence of inhibitory activity of heparin and other sulfated compounds in our experimental settings.…”

Broad‐Spectrum Antiviral Peptides and Polymers

“…[117] Therefore, a more complex architecture was designed as an alternative to PRO2000, a 16 kDa dendrimer functionalized with sodium 1-(carboxymethoxy) naphthalene 3,6-disulfonate labeled as SPL7013 (Figure 7A). SPL7013 inhibited HIV-1, HSV-1, and Huskens et al [ 114] Keller et al [ 115,117] Pirrone et al [ 116] SPL7013 (VivaGel) M n = 16 kDa See Figure 7A Rupp et al [ 118] Dezzutti et al [ 119] McGowan et al [ 120] Price et al [ 121] Carboxylate/phosphonate/sulfonate RAFT polymers M n from 1.8 to 84.7 kDa Schandock et al [ 123] Polyacrylamides containing benzoboroxole moieties obtained by free radical polymerization M n = 100 kDa Mahalingam et al [ 124] MUS-functionalized gold NPs ≈2.5 nm Cagno et al [ 5,125] HSV-2 infections in vitro and in animal models, even when administered post-infection. [118,119] There is evidence that the dendrimer inhibits both viral entry and replication, thus acting at different stages of infection.…”

“…Interestingly, additional studies demonstrated that the MUS-functionalized NPs were virucidal against influenza A (H1N1), though its mechanism for viral entry was independent of HSPGs and was instead enabled by the binding of viral particles to the sialic acid groups presented at the surface of host cells. [5] This activity was partly attributed to the affinity of influenza hemagglutinin protein to sulfate or sulfonate moieties, but also to the long alkyl spacer of MUS being an essential attribute for the inactivation of viral particles, as heparin was only weakly virustatic against H1N1. As promising in vivo efficacy was reported with MUS-functionalized NPs for the treatment of RSVinfected mice, further analyses on a wider range of viral strains were recommended.…”

“…[1][2][3][4] As vaccine development requires considerable time and is often ineffective against mutated viral strains, efficient broad-spectrum antiviral drugs are necessary to control and reduce infection rates of newly emerged viruses. [5] Although a large morphological diversity was observed across the different viral species, the main components of viruses are retained and optimized to transfer nucleic acid from cell-to-cell: DOI: 10.1002/adhm. 202101113 A virus particle (virion) is composed of genetic material, either single-or doublestranded RNA or DNA, protected by a protein coat (capsid) only (non-enveloped viruses) or a capsid surrounded in an outer envelope of proteins and lipids (enveloped viruses).…”

Cell entry inhibitor with sulfonated colloid gold as new potent broad-spectrum virucides

“…Gold nanoparticles coated with sulfonic acid inhibit different strains of influenza virus that do not bind HSPGs. The antiviral action is virucidal and irreversible for influenza A (H1N1, H3N2, and H5N1) and B virus strains (2).…”