Andrographolide and its fluorescent derivative inhibit the main proteases of 2019-nCoV and SARS-CoV through covalent linkage
Journal
Biochemical and Biophysical Research Communications
Journal Volume
533
Journal Issue
3
Pages
467-473
Date Issued
2020
Author(s)
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by 2019 novel coronavirus (2019-nCoV) has been a crisis of global health, whereas the effective vaccines against 2019-nCoV are still under development. Alternatively, utilization of old drugs or available medicine that can suppress the viral activity or replication may provide an urgent solution to suppress the rapid spread of 2019-nCoV. Andrographolide is a highly abundant natural product of the medicinal plant, Andrographis paniculata, which has been clinically used for inflammatory diseases and anti-viral therapy. We herein demonstrate that both andrographolide and its fluorescent derivative, the nitrobenzoxadiazole-conjugated andrographolide (Andro- NBD), suppressed the main protease (Mpro) activities of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV). Moreover, Andro-NBD was shown to covalently link its fluorescence to these proteases. Further mass spectrometry (MS) analysis suggests that andrographolide formed a covalent bond with the active site Cys145 of either 2019-nCoV Mpro or SARS-CoV Mpro. Consistently, molecular modeling analysis supported the docking of andrographolide within the catalytic pockets of both viral Mpros. Considering that andrographolide is used in clinical practice with acceptable safety and its diverse pharmacological activities that could be beneficial for attenuating COVID-19 symptoms, extensive investigation of andrographolide on the suppression of 2019-nCoV as well as its application in COVID-19 therapy is suggested. ? 2020 Elsevier Inc.
Subjects
2019-nCoV; Andrographolide; Main protease; SARS-CoV
SDGs
Other Subjects
andrographolide; cysteine; disulfiram; nctu 048; nitrobenzoxadiazole conjugated andrographolide; proteinase; recombinant enzyme; terpenoid; unclassified drug; 3C-like proteinase, Coronavirus; andrographolide; cysteine proteinase; diterpenoid; fluorescent dye; proteinase inhibitor; viral protein; antiviral activity; Article; binding affinity; controlled study; covalent bond; drug binding site; drug protein binding; drug structure; enzyme active site; enzyme activity; enzyme inhibition; IC50; in vitro study; molecular docking; molecular model; nonhuman; priority journal; SARS coronavirus; Severe acute respiratory syndrome coronavirus 2; Betacoronavirus; chemistry; enzymology; metabolism; protein conformation; protein multimerization; SARS coronavirus; Betacoronavirus; Catalytic Domain; Cysteine Endopeptidases; Diterpenes; Fluorescent Dyes; Molecular Docking Simulation; Protease Inhibitors; Protein Conformation; Protein Multimerization; SARS Virus; Viral Nonstructural Proteins
Type
journal article