Suramin interacts with the positively charged region surrounding the 5-fold axis of the EV-A71 capsid and inhibits multiple enterovirus A

Abstract

Suramin was previously shown to bind to the EV-A71 capsid through its naphthalenetrisulfonic acid groups, thereby reducing virus-cell binding and inhibiting viral replication. Here, we identify VP1-145 as the critical amino acid that accounts for the differential sensitivity of EVA-71 viruses to suramin. A single Q or G to E substitution at VP1-145 results in an approximately 30-fold shift of IC50 or IC90 values reproducing the inhibition profile observed with field isolates expressing either the 145Q or E mutation. Our data support the conclusion that suramin binds to the positively charged region surrounding the 5-fold axis of the capsid and consequently blocks the virus attachment and entry into host cells. In order to assess the antiviral-spectrum of suramin, we analyzed 18 representative enteroviruses: A (n = 7), B (n = 5), C (n = 5) and D (n = 1). We show that suramin potency is restricted to enterovirus A species. Clinical development of suramin is further supported by pharmacokinetic data demonstrating bioactive plasma levels after a single dose intramuscular administration in macaques. Altogether, our findings support the clinical development of suramin as a novel entry inhibitor for the treatment of enterovirus A infections.

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

“…This is in agreement with other studies that also reported on the inhibition of virus binding or entry by suramin (16,23,27). Several studies have suggested that negatively charged suramin molecules can bind to positive charges on virions (22,28,29). Our data suggest that the antiviral effect of suramin is primarily due to inhibition of an early step in the SARS-CoV-2 replication cycle, and we suspect that this is due to binding of the compound to SARS-CoV-2 virions, interfering with their binding to the cell receptor and possibly also inhibiting fusion.…”

Molecular epidemiology of coxsackievirus A6 derived from hand, foot, and mouth disease in Fukuoka between 2013 and 2017

“…Analyses of the amino acid changes in the VP1 gene suggested that CV‐A6 had changed its infectivity of the host and contributed to the development of anti‐EV drugs targeting capsid and a vaccine . In the current study, some mutations in the VP1 loops were detected, but this analysis was limited because only VP1 was investigated, despite capsid protein comprising VP1, VP2, and VP3 complexes.…”

The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1

“…Several clinical and preclinical studies have highlighted the pleiotropic beneficial effects of suramin on other clinical domains (8 -10, 13, 27-30). The discovery that suramin could prevent infection by several important viral pathogens, including Zika virus (12), herpes simplex virus (31), and others (11,13,27) might indicate that it has potential to be applied to treat multiple sexually transmitted infections.…”