Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections

Autor: Seungtaek Kim, Young Hee Jin, Daeui Park, Tamina Park, Chul Min Park, Sangeun Jeon, Jung Sun Min, Jihye Lee, Sunoh Kwon, Hyoung Rae Kim, Min Seong Jang, Jong Hwan Song
Jazyk: angličtina
Rok vydání: 2020
Předmět:
viruses
CoV
coronavirus
coronavirus
Pharmaceutical Science
remdesivir
MERS
Middle East respiratory syndrome coronavirus
Pharmacology
DMSO
dimethyl sulfoxide
medicine.disease_cause
RNA-dependent RNA polymerase
chemistry.chemical_compound
0302 clinical medicine
Chlorocebus aethiops
Drug Discovery
CDC
Centers for Disease Control and Prevention
Coronavirus
0303 health sciences
Alanine
Chemistry
Alkaloid
virus diseases
respiratory system
Phenanthridines
Molecular Docking Simulation
HIV
human immunodeficiency virus
Severe acute respiratory syndrome-related coronavirus
030220 oncology & carcinogenesis
HCV
hepatitis C virus
Middle East Respiratory Syndrome Coronavirus
Molecular Medicine
cell-based reporter assay
NAA
nucleoside analog antiviral
Antiviral Agents
Lycorine
Article
DMEM
Dulbecco's Modified Eagle's Medium
Viral Proteins
03 medical and health sciences
FBS
fetal bovine serum
medicine
Animals
SARS
severe acute respiratory syndrome
RdRp
RNA-dependent RNA polymerase
COVID-19
coronavirus infectious disease 2019
Amaryllidaceae Alkaloids
Vero Cells
IC50
MHV
mouse hepatitis virus
030304 developmental biology
SARS-CoV-2
NNA
non-nucleoside antiviral
COVID-19
Hydrogen Bonding
biochemical phenomena
metabolism
and nutrition
FDA
Food and Drug Administration
Adenosine Monophosphate
respiratory tract diseases
KNIH
Korea National Institute of Health
Complementary and alternative medicine
Docking (molecular)
Nucleoside
Zdroj: Phytomedicine
ISSN: 1618-095X
0944-7113
Popis: Highlights • Lycorine inhibited MERS-CoV, SARS-CoV, and SARS-CoV-2 infections. • Lycorine directly inhibited MERS-CoV RdRp activity. • Lycorine interacts with SARS-CoV-2 RdRp through hydrogen bonding. • Lycorine is a non-nucleoside direct-acting antiviral against emerging coronavirus.
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 IC50 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 IC50 of 1.406 ± 0.260 μM, compared with remdesivir's IC50 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.
Databáze: OpenAIRE
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