Abstract
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 (K D ) 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 IC 50 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 K D 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.
Keywords: (–)-epicatechin 3-O-caffeoate; Camellia sinensis; SARS-CoV-2; catechins; ebselen.
【저자키워드】 SARS-CoV-2, catechins, (–)-epicatechin 3-O-caffeoate, Camellia sinensis, ebselen., 【초록키워드】 3CLpro, surface plasmon resonance, SPR, inhibitors, binding energy, ECG, Ebselen, dissociation, Dissociation constant, Amino acid, cellular, AutoDock, Camellia sinensis, cysteine, gallate, surface plasmon, Previous studies, cysteine protease, chymotrypsin, amino acid residues, previous study, inhibitory activity, Gly143, HIS163, Modification, configuration, amino acid residue, detection system, Extracellular, Epicatechin, ASN142, THR26, GLN189, (-)-epicatechin, selected, was used, inhibit, conducted, suggested, Camellia, GCG, 【제목키워드】 molecular docking, Protease inhibitor, 3CL, cellular, Camellia sinensis,