RT Journal Article
SR Electronic
T1 Broad-Spectrum, Patient-Adaptable Inhaled Niclosamide-Lysozyme Particles are Efficacious Against Coronaviruses in Lethal Murine Infection Models
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.24.310490
DO 10.1101/2020.09.24.310490
A1 Ashlee D. Brunaugh
A1 Hyojong Seo
A1 Zachary Warnken
A1 Li Ding
A1 Sang Heui Seo
A1 Hugh D.C. Smyth
YR 2020
UL http://biorxiv.org/content/early/2020/09/24/2020.09.24.310490.abstract
AB Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, the oral formulation produces systemic drug levels that are too low to inhibit SARS-CoV-2. As an alternative, direct delivery of NIC to the respiratory tract as an aerosol could target the primary site of for SARS-CoV-2 acquisition and spread. We have developed a niclosamide powder suitable for delivery via dry powder inhaler, nebulizer, and nasal spray through the incorporation of human lysozyme (hLYS) as a carrier molecule. This novel formulation exhibits potent in vitro and in vivo activity against MERS-CoV and SARS-CoV-2 and protects against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure wide-spread utilization.Competing Interest StatementAn author (HDCS) of this paper consults for and has equity ownership in Respira Therapeutics, Nob Hill Therapeutics, Via Therapeutics, LLC and CloXero Therapeutics, Inc on inhaled product development. An author of this paper (ADB) is an employee of Via Therapeutics, LLC and has equity ownership in CloXero Therapeutics, Inc. An author of this paper (ZW) is an employee of Via Therapeutics, LLC. The terms of this arrangement have been reviewed and approved by the University of Texas at Austin in accordance with its policy on objectivity in research.