FDA approved drugs with broad anti-coronaviral activity inhibit SARS-CoV-2 in vitro

Stuart Weston; Rob Haupt; James Logue; Krystal Matthews; Matthew B. Frieman

In order to validate our screening process as a means to determine compounds with potential antiviral effect we decided to follow up with two drugs. It has been reported that chloroquine shows anti-SARS-CoV-2 effects in humans, so we further investigated hydroxychloroquine and chloroquine phosphate as both were present in our screen (Table 1) . To more directly assess the effects of these compounds on viral replication, Vero E6 cells were plated and pre-treated with drug prior to infection with SARS-CoV-2 at MOI 0.1. Supernatant was collected 24 h post-. CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.008482 doi: bioRxiv preprint infection to determine titer of virus by TCID50 assay and cells were collected in TRIzol to assess production of viral mRNA. Treatment with hydroxychloroquine or chloroquine both caused a reduction in viral mRNA levels, especially at higher concentrations (concentrations used were not cytotoxic - Fig. 1 and Table 1 ). There was a larger decrease in relative expression levels of RdRp that N mRNA, but both showed reductions across the range of concentrations used (Fig. 2) . Along with causing a reduction in viral mRNA, treatment with hydroxychloroquine or chloroquine caused a significant reduction in viral replication (Fig. 3) .