Discovery of Camellia sinensis catechins as SARS-CoV-2 3CL protease inhibitors through molecular docking, intra and extra cellular assays

Autor: Peng Zhang, Jia-Ping Ke, Guan-Hu Bao, Shi-Yu Liu, Wei Wang, Gang-Xiu Chu
Rok vydání: 2021
Předmět:
CG
(+)-catechin gallate
(–)-epicatechin 3-O-caffeoate
medicine.medical_treatment
SARS-CoV
severe acute respiratory syndrome coronavirus
ETFs
ester-type flavoalkaloids
Pharmaceutical Science
Article
Camellia sinensis
Catechin
GCG
(+)-gallocatechin gallate
KD
dissociation constants
Luc
Luciferase
ECG
(–)-epicatechin gallate
3CLpro
3-chymotrypsin-like cysteine protease
IC50
half-maximal inhibitory concentration
Drug Discovery
medicine
Extracellular
Humans
Flu
Fluminescence
Protease Inhibitors
catechins
Pharmacology
Protease
Tea
Chemistry
SARS-CoV-2
COVID-19
Gallate
EGCG
(–)-epigallocatechin gallate
AutoDock
Cysteine protease
Dissociation constant
Molecular Docking Simulation
Complementary and alternative medicine
Biochemistry
Docking (molecular)
Molecular Medicine
ebselen
RLU
Renilla luminescence
SPR
Surface plasmon resonance
Zdroj: Phytomedicine
ISSN: 1618-095X
Popis: Background and purpose Previous studies suggest that major Camellia sinensis (tea) catechins can inhibit 3-chymotrypsin-like cysteine protease (3CLpro), inspiring us to study 3CLpro inhibition of the recently discovered catechins from tea by our group. Methods Autodock was used to dock 3CLpro and 16 tea catechins. Further, a 3CLpro activity detection system was used to test their intra and extra cellular 3CLpro inhibitory activity. Surface plasmon resonance (SPR) was used to analyze the dissociation constant (KD) between the catechins and 3CLpro. Results Docking data suggested that 3CLpro interacted with the selected 16 catechins with low binding energy through the key amino acid residues Thr24, Thr26, Asn142, Gly143, His163, and Gln189. The selected catechins other than zijuanin D (3) and (-)-8-(5′'R)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (11) can inhibit 3CLpro intracellularly. The extracellular 3CLpro IC50 values of (–)-epicatechin 3-O-caffeoate (EC-C, 1), zijuanin C (2), etc-pyrrolidinone C and D (6), etc-pyrrolidinone A (9), (+)-gallocatechin gallate (GCG), and (-)-epicatechin gallate (ECG) are 1.58 ± 0.21, 41.2 ± 3.56, 0.90 ± 0.03, 46.71 ± 10.50, 3.38 ± 0.48, and 71.78 ± 8.36 µM, respectively. The KD values of 1, 6, and GCG are 4.29, 3.46, and 3.36 µM, respectively. Conclusion Together, EC-C (1), etc-pyrrolidinone C and D (6), and GCG are strong 3CLpro inhibitors. Our results suggest that structural modification of catechins could be conducted by esterificating the 3-OH as well as changing the configuration of C-3, C-3′'' or C-5′'' to discover strong SARS-CoV-2 inhibitors.
Graphical abstract Image, graphical abstract
Databáze: OpenAIRE
Externí odkaz: