Virucidal Potential of 3,3',4,4',5,5'-Hexahydroxy-trans-Stilbene Against Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infections have a significant impact on global health. Despite of recent advancements, the current treatment options for managing severe RSV infections remain primarily limited to supportive care, emphasizing the high priority for the development of effective antiviral therapies. Antiviral activity of 3,3',4,4',5,5'-hexahydroxy-trans-stilbene (HHS), a synthetic polyhydroxyphenol, has previously been demonstrated against SARS-CoV-2. In this study, we provide evidence for a direct virucidal effect of HHS against RSV infection in permissive HEp-2 cells in vitro. HHS, with an IC50 of 3.44 μM, efficiently inhibited HEp-2 cell infection with no sign of toxicity at least up to 25 μM. Interestingly, resveratrol, a polyhydroxyphenol analogue, was less efficient. Mode of action experiments revealed that HHS directly interacts with RSV particles, indicating that its virucidal activity is based on this interaction rather than affecting HEp-2 cells or post-infection processes. Together with previous data, our results suggest a broad antiviral activity of HHS against different respiratory viruses. Further studies are necessary to unveil the exact mechanism and evaluate the potential of HHS in the treatment of severe respiratory virus infections.