Fast and scalable lipid nanoparticle formulation of niclosamide (nano NCM) effectively inhibits SARS-CoV-2 replication in vitro

Wang, Guankui; Gaikwad, Hanmant; McCarthy, Mary K; Gonzalez-Juarrero, Mercedes; Li, Yue; Armstrong, Michael; Reisdorf, Nichole; Morrison, Thomas E; Simberg, Dmitri

As exemplified by the COVID-19 pandemic, highly infective respiratory viruses can spread rapidly in the population because of lack of effective approaches to control viral replication and spread. Niclosamide (NCM) is an old anthelminthic drug (World Health Organization essential medicine list) with pleiotropic pharmacological activities. Several recent publications demonstrated that NCM has broad antiviral activities and potently inhibits viral replication, including replication of SARS-CoV-2, SARS-CoV, and dengue viruses. Unfortunately, NCM is almost completely insoluble in water, which limits its clinical use. We developed a highly scalable and cost-effective nanoparticle formulation of NCM (nano NCM) using only FDA-approved excipient and demonstrated potency against SARS-CoV-2 infection in cells (Vero E6 and ACE2-expressing lung epithelium cells). Our ultimate goal is to develop the nano NCM formulation for treatment of COVID-19 patients.