Identification and Use of Niclosamide Analogs as Inhibitors of SARS-CoV-2 Infection

This technology includes the identification and use of niclosamide analogs and prodrugs for the treatment of SARS-CoV-2 infection. In-vitro studies have found niclosamide, an old anthelminthic drug, to be potent and effective against Covid-19. But the broad antiviral effect of niclosamide is offset by the low solubility of the drug, leading to poor oral absorption. The niclosamide analogs and prodrugs included in this technology have better in vitro physicochemical properties. Also, these analogs were comparable to niclosamide in the in-vitro 3D models of SARS-CoV-2 infection. Pharmacokinetic studies of a prodrug conducted in mice and hamsters has shown better absorbtion of the active niclosamide, with higher concentrations of niclosamide in both plasma and lungs (the primary site of COVID-19 disease manifestation). The oral bio-availability of niclosamide is greatly enhanced with this prodrug.