Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system.

Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01 µM). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.

Chromium behavior during thermal treatment of MSW fly ash.

Energy-from-waste incineration has been promoted as an environmentally responsible method for handling non-recyclable waste from households. Despite the benefits of energy production, elimination of organic residues and reduction of volume of waste to be landfilled, there is concern about fly ash disposal. Fly ash from an incinerator contains toxic species such as Pb, Zn, Cd and Cr which may leach into soil and ground water if landfilled. Thermal treatment of the fly ash from municipal solid waste has been tested and proposed as a treatment option for removal of metal species such as Pb, Cd and Zn, via thermal re-volatilization. However, Cr is an element that remains in the residue of the heat treated fly ash and appears to become more soluble. This Cr solubilization is of concern if it exceeds the regulatory limit for hazardous waste. Hence, this unexpected behavior of Cr was investigated. The initial work involved microscopic characterization of Cr in untreated and thermally-treated MSW fly ash. This was followed by determining leaching characteristics using standard protocol leaching tests and characterization leaching methods (sequential extraction). Finally, a mechanism explaining the increased solubilization was proposed and tested by reactions of synthetic chemicals.