Suramin Inhibits SARS-CoV-2 Infection in Cell Culture by Interfering with Early Steps of the Replication Cycle

Salgado-Benvindo, Clarisse; Thaler, Melissa; Tas, Ali; Ogando, Natacha S.; Bredenbeek, Peter J.; Ninaber, Dennis K.; Wang, Ying; Hiemstra, Pieter S.; Snijder, Eric J.; van Hemert, Martijn J.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that originated in Wuhan, China, in December 2019 has impacted public health, society, the global economy, and the daily lives of billions of people in an unprecedented manner. There are currently no specific registered antiviral drugs to treat or prevent SARS-CoV-2 infections. Therefore, drug repurposing would be the fastest route to provide at least a temporary solution while better, more specific drugs are being developed. Here, we demonstrate that the antiparasitic drug suramin inhibits SARS-CoV-2 replication, protecting Vero E6 cells with a 50% effective concentration (EC(50)) of ∼20 μM, which is well below the maximum attainable level in human serum. Suramin also decreased the viral load by 2 to 3 logs when Vero E6 cells or cells of a human lung epithelial cell line (Calu-3 2B4 [referred to here as “Calu-3”]) were treated. Time-of-addition and plaque reduction assays performed on Vero E6 cells showed that suramin acts on early steps of the replication cycle, possibly preventing binding or entry of the virus. In a primary human airway epithelial cell culture model, suramin also inhibited the progression of infection. The results of our preclinical study warrant further investigation and suggest that it is worth evaluating whether suramin provides any benefit for COVID-19 patients, which obviously requires safety studies and well-designed, properly controlled randomized clinical trials.