The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and indomethacin, alone or in combination, in reducing SARS-CoV-2 replication. In addition, the cytotoxicity of the drugs was evaluated. The findings showed that the combination of ketotifen with indomethacin (SJP-002C) or naproxen both reduce viral yield. Compared to ketotifen alone (60% inhibition at EC50), an increase in percentage inhibition of SARS-CoV-2 to 79%, 83% and 93% was found when co-administered with 25, 50 and 100 μM indomethacin, respectively. Compared to ketotifen alone, an increase in percentage inhibition of SARS-CoV-2 to 68%, 68% and 92% was found when co-administered with 25, 50 and 100 μM naproxen, respectively. For both drug combinations the observations suggest an additive or synergistic effect, compared to administering the drugs alone. No cytotoxic effects were observed for the administered dosages of ketotifen, naproxen, and indomethacin. Further research is warranted to investigate the efficacy of the combination of ketotifen with indomethacin (SJP-002C) or naproxen in the treatment of SARS-CoV-2 infection in humans.

A discovery-based undergraduate organic chemistry lab experiment has been developed in which students establish the diastereoselectivity of hydride reduction of the α-chiral ketone (±)-benzoin isopropyl ether to erythro and threo diastereomeric alcohols by two different reducing agents. Students achieve this goal by working collaboratively and using chemical, chromatographic (TLC), and NMR spectroscopic methods to identify the major diastereomers produced from each reduction. To this end, three groups of students perform three different reductions using three different reducing agents. Students in two groups carry out reduction of (±)-benzoin isopropyl ether: one uses NaBH 4 / ethanol, a widely used metal hydride reagent for reduction of aldehydes and ketones, and the other uses Al(O i Pr) 3 /2-propanol, a hydride transfer reagent used in the Meerwein−Ponndorf−Verley (MPV) reaction. Students in the third group use diisobutylaluminum hydride (DIBAL-H) to reductively ring-open meso-2,2-dimethyl-4,5-diphenyl-1,3-dioxolane (an acetal they synthesize in a previous experiment) to obtain an authentic sample of the erythro diastereomer unaccompanied by its threo counterpart. Students perform TLC analysis of NaBH 4 and MPV reaction products vs the authentic erythro sample to qualitatively establish the diastereoselectivity exhibited by NaBH 4 and MPV reduction of the ketone substrate. Afterward, students from all three groups share 1 H NMR spectra of their products and perform quantitative analysis by establishing the ratios of each diastereomer present using NMR integration values. Through experimentation, students learn how diastereomers can differ chromatographically and spectroscopically and yet not be readily distinguishable by such techniques. This experiment also serves as a pedagogically valuable complement to a previously described and highly popular discovery-based experiment that probes the diastereoselectivity in the NaBH 4 reduction of (±)-benzoin.