Graphical abstract Image, graphical abstract Background: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L’Hér.) Herb. and has various pharmacological bioactivities including antiviral function. Purpose: We investigated the direct-inhibiting action of lycorine on CoV’s RdRp, as potential treatment for emerging CoV infections. Methods: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp. Results: Lycorine efficiently inhibited these CoVs with IC 50 values of 2.123 ± 0.053, 1.021 ± 0.025, and 0.878 ± 0.022 μM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC 50 of 1.406 ± 0.260 μM, compared with remdesivir’s IC 50 value of 6.335 ± 0.731 μM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (−6.2 kcal/mol) were higher than those of remdesivir (−4.7 kcal/mol). Conclusions: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.
【저자키워드】 COVID-19, coronavirus, HIV, Human immunodeficiency virus, Remdesivir, RNA-dependent RNA polymerase, FBS, fetal bovine serum, DMSO, dimethyl sulfoxide, COVID-19, coronavirus infectious disease 2019, RdRp, RNA-dependent RNA polymerase, MHV, mouse hepatitis virus, DMEM, Dulbecco's modified Eagle's medium, SARS, Severe acute respiratory syndrome, CDC, Centers for Disease Control and Prevention, CoV, coronavirus, FDA, Food and Drug Administration, lycorine, cell-based reporter assay, HCV, hepatitis C virus, MERS, Middle East respiratory syndrome coronavirus, KNIH, Korea National Institute of Health, NAA, nucleoside analog antiviral, NNA, non-nucleoside antiviral,