Virucidal and Antiviral Activity of Astodrimer Sodium against SARS-CoV-2 in Vitro

33 Pages Posted: 28 Apr 2021

See all articles by Jeremy Paull

Jeremy Paull

Starpharma Pty Ltd

Graham Heery

Starpharma Pty Ltd

Michael Bobardt

The Scripps Research Institute - Department of Immunology and Microbiology

Alex Castellarnau

Starpharma Pty Ltd

Carolyn Luscombe

Starpharma Pty Ltd

Jacinth Fairley

Starpharma Pty Ltd

Philippe Gallay

The Scripps Research Institute - Department of Immunology and Microbiology

Date Written: March 24, 2021

Abstract

An effective response to the ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will involve a range of complementary preventive modalities. The current studies were conducted to evaluate the in vitro SARS-CoV-2 antiviral and virucidal 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 and Calu-3 cells, with 50% effective concentrations (EC50) for i) reducing virus-induced cytopathic effect of 0.002 to 0.012 mg/mL in Vero E6 cells, and ii) infectious virus release by plaque assay of 0.019 to 0.032 mg/mL in Vero E6 cells and 0.031 to 0.037 mg/mL in Calu-3 cells. The selectivity index (SI) in these assays was as high as 2197. Astodrimer sodium was also virucidal, reducing SARS-CoV-2 infectivity by >99.9% (>3 log10) within 1 minute of exposure, and up to >99.999% (>5 log10) shown at astodrimer sodium concentrations of 10 to 30 mg/mL in Vero E6 and Calu-3 cell lines. Astodrimer sodium also inhibited infection in a primary human airway epithelial cell line. The data were similar for all investigations and were consistent with the potent antiviral and virucidal 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 attachment of the virus to 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.

Note: Funding Statement: The research was funded by Starpharma Pty Ltd, which was responsible for study design, interpretation of data, writing the manuscript and decision to submit the article for publication.

Declaration of Interests: The authors declare the following financial interests that may be considered as potential competing interests: J.R.A.P., J.K.F. and G.P.H. are paid employees of Starpharma Pty Ltd. A.C. and C.A.L. are paid consultants to Starpharma Pty Ltd.

Keywords: Astodrimer, COVID-19, dendrimer, antiviral, SARS-CoV-2, SPL7013

Suggested Citation

Paull, Jeremy and Heery, Graham and Bobardt, Michael and Castellarnau, Alex and Luscombe, Carolyn and Fairley, Jacinth and Gallay, Philippe, Virucidal and Antiviral Activity of Astodrimer Sodium against SARS-CoV-2 in Vitro (March 24, 2021). Available at SSRN: https://ssrn.com/abstract=3830085 or http://dx.doi.org/10.2139/ssrn.3830085

Jeremy Paull (Contact Author)

Starpharma Pty Ltd ( email )

4-6 Southampton Crescent
Abbotsford, Victoria 3067
Australia

Graham Heery

Starpharma Pty Ltd ( email )

4-6 Southampton Crescent
Abbotsford, Victoria 3067
Australia

Michael Bobardt

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

Alex Castellarnau

Starpharma Pty Ltd ( email )

4-6 Southampton Crescent
Abbotsford, Victoria 3067
Australia

Carolyn Luscombe

Starpharma Pty Ltd ( email )

4-6 Southampton Crescent
Abbotsford, Victoria 3067
Australia

Jacinth Fairley

Starpharma Pty Ltd ( email )

4-6 Southampton Crescent
Abbotsford, Victoria 3067
Australia

Philippe Gallay

The Scripps Research Institute - Department of Immunology and Microbiology ( email )

La Jolla, CA 92037
United States

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
288
Abstract Views
2,250
rank
127,800
PlumX Metrics