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

Abstract

Abstract The ongoing COVID-19 pandemic continues to pose a major public health burden around the world. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over one million people worldwide as of April, 2020, and has led to the deaths of nearly 300,000 people. No approved vaccines or treatments in the USA currently exist for COVID-19, so there is an urgent need to develop effective countermeasures. The IMPDH inhibitor merimepodib (MMPD) is an investigational antiviral drug that acts as a noncompetitive inhibitor of IMPDH. It has been demonstrated to suppress replication of a variety of emerging RNA viruses. We report here that MMPD suppresses SARS-CoV-2 replication in vitro. After overnight pretreatment of Vero cells with 10 μM of MMPD, viral titers were reduced by 4 logs of magnitude, while pretreatment for 4 hours resulted in a 3-log drop. The effect is dose-dependent, and concentrations as low as 3.3 μM significantly reduced viral titers when the cells were pretreated prior to infection. The results of this study provide evidence that MMPD may be a viable treatment option for COVID-19.