Abstract
Aims: Flavonoids and related compounds, such as quercetin-based antiviral drug Gene-Eden-VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS-CoV proteases. In this study, we aimed to compare the anti-SARS CoV-2 activities of both newly synthesized chalcone derivatives and these two drugs.
Methods: Determination of the potent antiviral activity of newly synthesized chalcone derivatives against SARS-CoV-2 by calculating the RT-PCR cycling threshold (C t ) values.
Results: Antiviral activities of the compounds varied because of being dose dependent. Compound 6, 7, 9, and 16 were highly effective against SARS-CoV-2 at the concentration of 1.60 µg/mL. Structure-based virtual screening was carried out against the most important druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase, to identify putative inhibitors that could facilitate the development of potential anti-coronavirus disease-2019 drug candidates.
Conclusions: Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from -4.370 to -2.748 kcal/mol along with their toxicological, ADME, and drug-like properties.
【초록키워드】 SARS-CoV-2, coronavirus, SARS-CoV, drugs, quercetin, flavonoids, Virtual screening, protease, antiviral activity, severe acute respiratory syndrome Coronavirus, RT-PCR, ADME, binding affinity, antiviral drug, activity, flavonoid, chalcone, RNA-dependent RNA polymerase, Viral RNA, targets, Proteases, RNA polymerase, inhibitor, threshold, compounds, Concentration, dose, antiviral activities, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, viral RNA-dependent RNA polymerase, drug candidates, Compound, derivative, Cycling, effective, identify, carried, inhibit, eight, facilitate, analysis, inhibiting, Angelica, Determination, 【제목키워드】 SARS-CoV-2, derivative, effective, New,