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, IC 50 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 IC 50 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 IC 50 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.
【초록키워드】 COVID-19, Treatment, SARS-CoV-2, Efficacy, pandemic, Antiviral, sodium, Remdesivir, Virtual screening, molecular dynamics, in vitro, monoclonal antibodies, anti-SARS-CoV-2, inhibitors, database, COVID-19 treatment, SARS-CoV-2 variants, targets, molecular, immunofluorescence, Beta variant, in vivo, compounds, Mpro protein, RMSD, surface area, selectivity index, inhibitors of SARS-CoV-2, severe acute respiratory coronavirus, positive control, SARS-CoV-2 protein, beta variants, continuum, Severe acute respiratory coronavirus-2, protein-ligand interaction, Protein target, usnic acid, caused, investigated, required, was performed, calculated, treatment for COVID-19, was selected, 【제목키워드】 in vitro, In silico method, inhibitors of SARS-CoV-2,