Special-formulation-of-inhaled-niclosamide-may-be-effective-against-SARS-CoV-2

Healthcare systems worldwide are overwhelmed by the raging COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the current number of global infections of SARS-CoV-2 nears 33 million individuals. An effective treatment or vaccine option is crucial and desperately needed.

The SARS-CoV-2 virus is related to the earlier coronaviruses of SARS-CoV and the Middle East respiratory syndrome-related coronavirus (MERS-CoV).  Now in new research published on the preprint server bioRxix*. A novel formulation of the drug Niclosamide (NIC) is observed to be effective against  SARS-CoV-2 and MERS-CoV in mouse models; it also protects against methicillin-resistance Staphylococcus aureus pneumonia and inflammatory lung damage. As oral formulation does not meet the required systemic concentration, this drug is delivered as an aerosol, using human lysozyme (hLYS) as a carrier molecule.

Micronized niclosamide (A) was embedded in a matrix of human lysozyme and stabilizers using spray drying (B). This novel system was developed as an alternative to traditional lactose-based carrier systems (C) and enabled the targeted respiratory delivery of NIC as a powder via DPI or a reconstituted suspension via nebulizer or nasal spray. The optimized formulation exhibited a size distribution that was appropriate for inhalation (i.e., geometric median diameter < 5 μm) in both the dry powder state as well as when reconstituted using water or 0.45% NaCl (D). Similar effects could not be achieved when a negatively charged protein, bovine serum albumin, was substituted in the formulation for the positively charged hLYS (E). Though hLYS is surface active, it appeared to only slightly enhance the dissolution of NIC compared to NIC particles blended with lactose (F). A respirable droplet size distribution could be achieved with multiple different reconstituted concentrations when nebulized using the Aerogen Solo (G). These concentrations resulted in no aggregation to the lysozyme component. Efficient aerosol delivery was achieved with both the nebulizer and disposable DPI, with ~50% of the emitted dose being of an appropriate size for lung deposition. This was significantly improved compared to a traditional lactose carrier particle system (H). Reproducible plume geometry could be achieved using a variety of reconstituted concentrations when actuated using the Aptar device (I). Data is presented as mean + SEM (n = 3). *p < 0.05, using two-way ANOVA with Tukey’s multiple comparisons test (comparisons of DPIs presented only).

In a strategy to assess and repurpose previously used drugs (against SARS-CoV and MERS-CoV), Ashlee D. Brunaugh et al. choose an FDA-approved anthelmintic (antiparasitic) drug called niclosamide (NIC) to study as a promising antiviral candidate. Niclosamide is listed as an Essential Medicine by WHO and has been in use for over 60 years. In their paper, the authors show the antiviral, antibacterial, and anti-inflammatory efficacy of the NIC-hLYS powders evaluated in vitro and in vivo in MERS-CoV SARS-CoV-2 infected mouse models. Utilizing repurposed NIC with lysozyme, the study reports developing a therapeutically effective, rapidly scalable and globally distributable antiviral therapy to reduce the spread of SARS-CoV-2.

Source: News Medical