Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro

Abstract

An effective response to the ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will require a range of complementary preventive modalities. The current studies were conducted to evaluate the in vitro SARS-CoV-2 antiviral activity of astodrimer sodium, a dendrimer with broad spectrum antimicrobial activity, including against enveloped viruses in in vitro and in vivo models, that is marketed for antiviral and antibacterial applications. We report that astodrimer sodium inhibits replication of SARS-CoV-2 in Vero E6 cells when added to cells 1-hour prior to or 1-hour post infection, with 50% effective concentrations reducing virus-induced cytopathic effect (EC50) ranging from 0.090 to 0.742 μM (0.002 to 0.012 mg/mL). The selectivity index (SI) in these assays was as high as 2197. Astodrimer sodium was also effective in a virucidal evaluation when mixed with virus for 1 hour prior to infection of cells (EC50 1.83 μM [0.030 mg/mL]). Results from a time of addition study, which showed infectious virus was below the lower limit of detection at all time points tested, were consistent with the compound inhibiting early virus entry steps. The data were similar for all investigations and were consistent with the potent antiviral activity of astodrimer sodium being due to inhibition of virus-host cell interactions, as previously demonstrated for other viruses. Further studies will confirm if astodrimer sodium binds to SARS-CoV-2 spike protein and physically blocks initial association of the virus with heparan sulfate proteoglycans on the host cell. Given the in vitro effectiveness and significantly high SI, astodrimer sodium warrants further investigation for potential as a nasally administered or inhaled antiviral agent for SARS-CoV-2 prevention and treatment applications.

Peptides and Dendrimers: How to Combat Viral and Bacterial Infections

“…It is still not commercially available for the prevention of STIs in any countries. Furthermore, it also shows significant activity against other viruses, such as the novel coronavirus SARS-CoV-2 [ 172 ], enabling a fast-track development of tools to fight COVID-19.…”

Highly Branched Polymers Based on Poly(amino acid)s for Biomedical Application

“…The 32 amino groups present at the surface of this dendrimer were derivatized with sodium 1-(carboxymethoxy) naphthalene-3,6-disulfonate, thus generating a p( L -Lys) dendrimer with an anionic surface charge, with the commercial name astodrimer sodium. Paull et al evaluated the antiviral activity of SPL7013 and found that it inhibits replication of SARS-CoV-2 in Vero E6 cells when added to cells one hour prior to, or one hour post infection [ 67 ], in a way similar as observed previously for the inhibition of HIV [ 68 ]. Since it is a dendrimer-based antiviral compound, inhalability is possible, and the authors conclude that SPL7013 warrants investigation for nasal administration to aid in preventing viral transmission and that it could be useful in the treatment of SARS-CoV-2.…”

Industry Update: the Latest Developments in the Field of Therapeutic delivery, September 2020

“…The nanoparticle formulation also demonstrates extended release of the drug which may offer opportunity for reduced administration frequency, further enhancing patient convenience [45]. Starpharma also have a dendrimer-based antiviral nasal spray, SPL7013, in development, the mode of action of which appears to be binding of the active agent to the virus spike protein and inhibiting its ability to enter host cells [46,47].…”