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The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with more than 780,000 deaths worldwide (as of 20 August 2020). To develop antiviral interventions quickly, drugs used for the treatment of unrelated diseases are currently being repurposed to treat COVID-19. Chloroquine is an anti-malaria drug that is used for the treatment of COVID-19 as it inhibits the spread of SARS-CoV-2 in the African green monkey kidney-derived cell line Vero1-3. Here we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells4, renders SARS-CoV-2 infection of Vero cells insensitive to chloroquine. Moreover, we report that chloroquine does not block infection with SARS-CoV-2 in the TMPRSS2-expressing human lung cell line Calu-3. These results indicate that chloroquine targets a pathway for viral activation that is not active in lung cells and is unlikely to protect against the spread of SARS-CoV-2 in and between patients.

Background Sibutramine, a serotonin and norepinephrine transporter blocker, is used as adjunctive obesity treatment. Studies in healthy subjects suggested that sibutramine might have opposing effects on peripheral and central sympathetic activity; an increase in blood pressure has been claimed. Direct measurements of muscle sympathetic nerve activity (MSNA) in sibutramine-treated patients have not been conducted. Methods and Results Twenty nondiabetic obese men and women completed the study (mean body mass index, 35 ± 3 kg/m2; mean age, 42 ± 8 years). They were treated for 5 days with 15 mg sibutramine per day or matching placebo in a randomized, double-blind, crossover fashion. At the end of each intervention, heart rate, blood pressure, and MSNA were recorded. Patients underwent cold pressor testing and phenylephrine and nitroprusside infusions. Results The mean blood pressure (systolic/diastolic) was 118 ± 13 mm Hg/70 ± 9 mm Hg with placebo and 120 ± 13 mm Hg/69 ± 8 mm Hg with sibutramine (P=.29). The mean resting MSNA was 28 ± 14 bursts/min with placebo and 12 ± 10 bursts/min with sibutramine (P < .0001). Sibutramine attenuated the rise in blood pressure (25 ± 9 mm Hg/9 ± 9 mm Hg versus 31 ± 12 mm Hg/14 ± 9 mm Hg, P < .01) and MSNA (0.3 ± 0.5 arbitrary units/min versus 1.0 ± 1.1 arbitrary units/min, P=.01) in response to cold pressor testing. Baroreflex heart rate control was similar with sibutramine and with placebo. The sympathetic baroreflex was shifted such that at a given blood pressure, MSNA was substantially decreased (top, 44 ± 1.23 bursts/min versus 58 ± 2.99 bursts/min [P < .001]; center point, 65 ± 0.32 mm Hg versus 67 ± 0.81 mm Hg [P < .05]). Conclusions Sibutramine treatment profoundly and selectively reduces sympathetic nerve traffic at rest and attenuates the responsiveness to sympathetic stimuli. Our data support the idea that sibutramine's peripheral sympathomimetic effect is counteracted by a central sympatholytic mechanism. Clinical Pharmacology & Therapeutics (2006) 79, 500–508; doi: 10.1016/j.clpt.2006.02.002