Neutralizing activity of Usnic acid and -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 beta-cyclodextrins (beta-CDs), a pharmaceutical excipient used to improve drug solubility. The cytotoxic activity, tested on Vero E6 cells, revealed no effect for beta-CDs alone whereas significant cytotoxicity for the UA /beta-CDs complex was recorded at concentrations >= 0.05%. The neutralizing activity towards the fusion of SARS-CoV-2 Spike Pseudovirus showed no effects for beta-CDs alone whereas the UA /beta-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 /beta-CDs complex could be useful in SARS-CoV-2 infection. [GRAPHICS]