Neutralizing activity of usnic acid and β-cyclodextrins complex against SARS-CoV-2 spike pseudovirus

: The rapid spread of SARS-CoV-2 and its infection severity require an urgent development of antiviral agents. In this respect, Usnic acid (UA), a natural dibenzofuran derivative, exerts antiviral activity against several viruses, though presenting very low solubility and high cytotoxicity. Here, UA was complexed with β-cyclodextrins (β-CDs), a pharmaceutical excipient used to improve drug solubility. The cytotoxic activity, tested on Vero E6 cells, revealed no effect for β-CDs alone whereas significant cytotoxicity for the UA/β-CDs complex was recorded at concentrations ≥ 0.05%. The neutralizing activity towards the fusion of SARS-CoV-2 Spike Pseudovirus showed no effects for β-CDs alone whereas the UA/β-CDs complex, when pre-incubated with the viral particles, efficiently inhibited the Pseudoviral fusion of about 90 and 82% at non-cytotoxic concentrations of 0.03 and 0.01%, respectively. In conclusion, although further evidences are needed to clarify the exact inhibition mechanism, UA/β-CDs complex could be useful in SARS-CoV-2 infection.