Abstract
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, administration of the currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formulation of NIC with an endogenous protein, human lysozyme (hLYS), could enable the direct aerosol delivery of the drug to the respiratory tract as an alternative to oral delivery, thereby effectively treating COVID-19 by targeting the primary site of SARS-CoV-2 acquisition and spread. To test this hypothesis, we engineered and optimized composite particles containing NIC and hLYS suitable for delivery to the upper and lower airways via dry powder inhaler, nebulizer, and nasal spray. The novel formulation demonstrates potent in vitro and in vivo activity against two coronavirus strains, MERS-CoV and SARS-CoV-2, and may offer protection against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to SARS-CoV-2 infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure rapid clinical development and wide-spread utilization.
Highlights
The Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-associated coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020 [1]
NIC-human lysozyme (hLYS) particles (0.7% w/w NIC) were administered at varying doses to Vero E6 cells infected with MERS-CoV or SARS-CoV-2, and the half maximal effective concentration (EC50) was calculated based upon observed cytopathic effect (CPE)
At the highest dose tested (0.125 μg/mL NIC), Vero cells with an established MERS-CoV infection exhibited an 82.2% ± 0.4% decrease in viral load compared to untreated controls after 24-hours of exposure to NIChLYS particles (Fig 1D)
Summary
The Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-associated coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020 [1]. A rapid and continuing rise in cases worldwide followed this declaration which has overwhelmed healthcare systems [2, 3]. There are limited treatment and vaccination options for coronaviruses, and outbreaks are expected to continue potentially into 2025 [4]. To address the ongoing pandemic, it is necessary that treatments are made rapidly available and at low-cost to patients and clinicians worldwide.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have