| Property | Value |
|---|
|
?: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.
|
|
is
?:annotates
of
|
|
|
?:creator
|
|
|
?:doi
|
-
10.1016/j.phymed.2020.153440
|
|
?:doi
|
|
|
?:journal
|
|
|
?:license
|
|
|
?:pdf_json_files
|
-
document_parses/pdf_json/03e8d802292808f2e594b06629bb72f13f91e3b5.json
|
|
?:pmc_json_files
|
-
document_parses/pmc_json/PMC7738280.xml.json
|
|
?:pmcid
|
|
|
?:pmid
|
|
|
?:pmid
|
|
|
?:publication_isRelatedTo_Disease
|
|
|
is
?:relation_isRelatedTo_publication
of
|
|
|
?:sha_id
|
|
|
?:source
|
|
|
?:title
|
-
Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections
|
|
?:type
|
|
|
?:year
|
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}