The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an 
ongoing global pandemic of severe pneumonia-like disease designated as 
coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed 
cases and 139,500 deaths have been reported worldwide, and there are currently 
no medical countermeasures available to prevent or treat the disease. As the 
development of a vaccine could require at least 12-18 months, and the typical 
timeline from hit finding to drug registration of an antiviral is >10 years, 
repositioning of known drugs can significantly accelerate the development and 
deployment of therapies for COVID-19. To identify therapeutics that can be 
repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs 
encompassing approximately 12,000 clinical-stage or FDA-approved small 
molecules. Here, we report the identification of 30 known drugs that inhibit 
viral replication. Of these, six were characterized for cellular dose-activity 
relationships, and showed effective concentrations likely to be commensurate 
with therapeutic doses in patients. These include the PIKfyve kinase inhibitor 
Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 
5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have 
advanced into the clinic, the known pharmacological and human safety profiles of 
these compounds will accelerate their preclinical and clinical evaluation for 
COVID-19 treatment.