tetano
Editor, Senior Moderator
PLoS One
. 2021 Feb 11;16(2):e0246803.
doi: 10.1371/journal.pone.0246803. eCollection 2021.
Development and evaluation of inhalable composite niclosamide-lysozyme particles: A broad-spectrum, patient-adaptable treatment for coronavirus infections and sequalae
Ashlee D Brunaugh[SUP] 1 [/SUP], Hyojong Seo[SUP] 1 [/SUP], Zachary Warnken[SUP] 1 [/SUP], Li Ding[SUP] 1 [/SUP], Sang Heui Seo[SUP] 2 [/SUP], Hugh D C Smyth[SUP] 1 [/SUP]
Affiliations
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.
. 2021 Feb 11;16(2):e0246803.
doi: 10.1371/journal.pone.0246803. eCollection 2021.
Development and evaluation of inhalable composite niclosamide-lysozyme particles: A broad-spectrum, patient-adaptable treatment for coronavirus infections and sequalae
Ashlee D Brunaugh[SUP] 1 [/SUP], Hyojong Seo[SUP] 1 [/SUP], Zachary Warnken[SUP] 1 [/SUP], Li Ding[SUP] 1 [/SUP], Sang Heui Seo[SUP] 2 [/SUP], Hugh D C Smyth[SUP] 1 [/SUP]
Affiliations
- PMID: 33571320
- DOI: 10.1371/journal.pone.0246803
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.