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Broad-spectrum, patient-adaptable inhaled niclosamide-lysozyme particles are efficacious against coronaviruses in lethal murine infection models
bioRxiv - Pharmacology and Toxicology Pub Date : 2020-10-07 , DOI: 10.1101/2020.09.24.310490
Ashlee D. Brunaugh , Hyojong Seo , Zachary Warnken , Li Ding , Sang Heui Seo , Hugh D.C. Smyth

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.

中文翻译:

广谱,适合患者的吸入型新氯酰胺酰胺溶菌酶颗粒可在致命的鼠类感染模型中有效抵抗冠状病毒

Niclosamide(NIC)已证明对SARS-CoV-2(COVID-19大流行的病原体)具有良好的体外抗病毒功效。尽管NIC已经获得FDA批准,但口服制剂产生的全身药物水平过低,无法抑制SARS-CoV-2。作为替代方案,将NIC作为气溶胶直接递送至呼吸道可能靶向SARS-CoV-2采集和传播的主要部位。我们已经开发了适合通过干粉吸入器,雾化器和鼻喷雾剂通过掺入人类溶菌酶(hLYS)作为载体分子的烟酰胺类粉末。这种新颖的制剂对MERS-CoV和SARS-CoV-2表现出强大的体外和体内活性,并能抵抗耐甲氧西林的金黄色葡萄球菌肺炎和炎症性肺损伤。
更新日期:2020-10-08
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