Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle

Abstract

47The SARS-CoV-2 pandemic that originated from Wuhan, China, in December 2019 has impacted public 48 health, society and economy and the daily lives of billions of people in an unprecedented manner. 49There are currently no specific registered antiviral drugs to treat or prevent SARS-CoV-2 infections. 50Therefore, drug repurposing would be the fastest route to provide at least a temporary solution while 51 better, more specific drugs are being developed. Here we demonstrate that the antiparasitic drug 52 suramin inhibits SARS-CoV-2 replication, protecting Vero E6 cells with an EC50 of ~20 µM, which is well 53 below the maximum attainable level in human serum. Suramin also decreased the viral load by 2-3 54 logs when Vero E6 cells or cells of a human lung epithelial cell line (Calu-3) were treated. Time of 55 addition and plaque reduction assays showed that suramin acts on early steps of the replication cycle, 56possibly preventing entry of the virus. In a primary human airway epithelial cell culture model, suramin 57 also inhibited the progression of infection.

Computational Identification of Human Biological Processes and Protein Sequence Motifs Putatively Targeted by SARS-CoV-2 Proteins Using Protein–Protein Interaction Networks

“…Our GO clustering analyses detected clusterings of great significance for annotations such as establishment of RNA localization, cell projection, lyase activity, cell cycle, and more. These fall in line with the current literature that describes such disturbances upon SARS-CoV-2 infection 44 − 46 and could also represent putative therapeutic targets. This collection of GO terms also helps shed light on the host mechanisms hijacked by SARS-CoV-2.…”

The repurposed drugs suramin and quinacrine inhibit cooperativelyin vitroSARS-CoV-2 3CLpro

“…In contrast, chloroquine has a weak effect on 3CL pro proteolytic activity. Suramin and quinacrine possess an anti-viral effect against SARS-CoV-2 in cell culture (da Silva et al, 2020; Duan et al, 2020; Roldan et al, 2020; Touret and de Lamballerie, 2020), however, the target protein of both molecules in the viral replication process was not identified. Based on the primary inhibition results, quinacrine and suramin were further investigated regarding their inhibitory potential, and our results demonstrate that suramin and quinacrine have an inhibitory effect against the 3CL protease of SARS-CoV-2 (Figures 2 and 3, respectively) .…”

“…Thus, repurposing of existing drug molecules could be a rapid alternative to combat the virus infection. The well described anti-parasitic drugs like chloroquine, quinacrine and suramin revealed anti-viral effects against SARS-Cov-2 in cell cultures (Liu et al, 2020; da Silva et al, 2020; Duan et al, 2020; Roldan et al, 2020; Touret and de Lamballerie, 2020). These three compounds have been used as antiprotozoal drugs, being that chloroquine and quinacrine are used against malaria (Hoekenga, 1955; Joy, 1999) and suramin against sleeping sickness, which is caused by trypanosomes (Steverding, 2010).…”

Preferential recognition and antagonism of SARS-CoV-2 spike glycoprotein binding to 3-O-sulfated heparan sulfate

“…Such high potencies could be advantageously translated into potential drug candidates, as proposed by the Turnbull group in the form of a clinical-stage heparan sulfate mimetic ( 54 ). Suramin, a small molecule mimetic of heparin, has also been presented as an inhibitor of early steps of SARS-CoV-2 infection ( 55 ).…”