The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro

Natalya Bukreyeva; Emily K. Mantlo; Rachel A. Sattler; Cheng Huang; Slobodan Paessler; Jerry Zeldis

Vero cells (CCL-81, ATCC) were maintained in Dulbecco's modified eagle medium (Hyclone) supplemented with 10% FBS (Gibco) and 1% penicillin and streptomycin solution (Hyclone). The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.07.028589 doi: bioRxiv preprint of each dilution was added in quadruplicates to Vero cells grown in a 96-well plate. Cells were incubated 4 days at 37°C. Cells were then fixed with 10% formalin for 30 minutes and stained for 5 minutes with crystal violet. Biological triplicates were harvested at each timepoint and statistical significance was determined via one-tailed t-test. We also tested T-705, another broad-spectrum antiviral that acts as a nucleoside analog. Both overnight and 4-hour pretreatment with high doses (33-100 μM) of T-705 failed to inhibit SARS-CoV-2 replication. Overall, our results indicate that therapeutic concentrations of MMPD, but not T-705, is effective in reducing SARS-COV-2 coronavirus titers.