(+)-Usnic acid and its salts, inhibitors of SARS‐CoV‐2, identified by using in silico methods and in vitro assay

Abstract

The pandemic caused by severe acute respiratory Coronavirus-2 (SARS-CoV-2) has been ongoing for over two years, and treatment for COVID-19, other than monoclonal antibodies, is urgently required. Accordingly, we have investigated the inhibitors of SARS-CoV-2 protein targets by high-throughput virtual screening using a marine natural products database. Considering the calculated molecular properties and availability of the compounds, (+)-usnic acid was selected as a suitable hit. In the in vitro antiviral assay of (+)-usnic acid by the immunofluorescence method, IC50 was 7.99 μM, which is similar to that of remdesivir used as a positive control. The generalized Born and surface area continuum solvation (MM/GBSA) method was performed to find the potent target of (+)-usnic acid, and the Mpro protein showed the most prominent value, −52.05 kcal/mol, among other SARS-CoV-2 protein targets. Thereafter, RMSD and protein–ligand interactions were profiled using molecular dynamics (MD) simulations. Sodium usnate (NaU) improved in vitro assay results with an IC50 of 5.33 μM and a selectivity index (SI) of 9.38. Additionally, when (+)-usnic acid was assayed against SARS-CoV-2 variants, it showed enhanced efficacy toward beta variants with an IC50 of 2.92 μM and SI of 11.1. We report the in vitro anti-SARS-CoV-2 efficacy of (+)-usnic acid in this study and propose that it has the potential to be developed as a COVID-19 treatment if its in vivo efficacy has been confirmed.

Advances in Research on Bioactivity, Toxicity, Metabolism, and Pharmacokinetics of Usnic Acid In Vitro and In Vivo

“…In a recent study, usnic acid and its salts against SARS-CoV-2 were tested by using in silico methods and in vitro assays [ 79 ]. High-throughput virtual screening using a marine natural product database was used in investigating the inhibitors of SARS-CoV-2 protein targets.…”

Effects of Usnic Acid to Prevent Infections by Creating a Protective Barrier in an In Vitro Study

“…The clinical real-life benefits of HPMC in the nose depend on its efficiency gelling property to trap all particles present in the air [ 8 ]. Indeed, there are studies that explore the opportunity to add other ingredients such as antimicrobial drugs of natural origin to the gelling barrier [ 10 ]. There are natural substances with antiviral effects that could be an interesting starting point for developing a strategy to control the infectious diseases [ 11 ].…”

“…There are natural substances with antiviral effects that could be an interesting starting point for developing a strategy to control the infectious diseases [ 11 ]. One of these is usnic acid (UA), a dibenzofuran derived from lichen [ 10 ]. UA exists in two enantiomeric forms, depending on the position of the methyl group at the chiral atom, which have no substantial differences in physical properties, but have significant differences in their biological and pharmacological activity [ 12 ].…”

Safety in Rats of a Novel Nasal Spray Formulation for the Prevention of Airborne Viral Infections

“…By binding SARS-CoV-2 Spike protein, UA could contribute to the retention of viral particles into the hydrogel produced by HPMC. UA and remdesivir (a product recently approved for the treatment of COVID-19) showed a similar activity in a SARS-CoV-2 binding assay [ 44 ]. Finally, an in vitro study performed on Vero E6 cells showed a significant activity of UA against three different strains of SARS-CoV-2, namely Wuhan, Delta, and Omicron [ 45 ].…”