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GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2.
Biomed Pharmacother. 2021 Oct; 142:112011.BP

Abstract

Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 μg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation.

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Authors+Show Affiliations

Tsai MS
Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Faculty of Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Yang YH
Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Chinese medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Lin YS
Department of Pharmacy, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Chang GH
Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Faculty of Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Hsu CM
Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Faculty of Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Yeh RA
Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Shu LH
Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Cheng YC
Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Liu HT
Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Wu YH
Department of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
Wu YH
Department of Electrical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Shen RC
Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Wu CY
Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Chinese medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan. Electronic address: smbepigwu77@gmail.com.

MeSH

Angiotensin-Converting Enzyme 2Antibodies, NeutralizingAntioxidantsAntiviral AgentsBiflavonoidsCOVID-19CatechinDrug DiscoveryGallic AcidHEK293 CellsHumansMedicine, East Asian TraditionalMutationProtein BindingProtein Interaction Domains and MotifsSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34388530

Citation

Tsai, Ming-Shao, et al. "GB-2 Blocking the Interaction Between ACE2 and Wild Type and Mutation of Spike Protein of SARS-CoV-2." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 142, 2021, p. 112011.
Tsai MS, Yang YH, Lin YS, et al. GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2. Biomed Pharmacother. 2021;142:112011.
Tsai, M. S., Yang, Y. H., Lin, Y. S., Chang, G. H., Hsu, C. M., Yeh, R. A., Shu, L. H., Cheng, Y. C., Liu, H. T., Wu, Y. H., Wu, Y. H., Shen, R. C., & Wu, C. Y. (2021). GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 142, 112011. https://doi.org/10.1016/j.biopha.2021.112011
Tsai MS, et al. GB-2 Blocking the Interaction Between ACE2 and Wild Type and Mutation of Spike Protein of SARS-CoV-2. Biomed Pharmacother. 2021;142:112011. PubMed PMID: 34388530.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2. AU - Tsai,Ming-Shao, AU - Yang,Yao-Hsu, AU - Lin,Yu-Shih, AU - Chang,Geng-He, AU - Hsu,Cheng-Ming, AU - Yeh,Reming-Albert, AU - Shu,Li-Hsin, AU - Cheng,Yu-Ching, AU - Liu,Hung-Te, AU - Wu,Yu-Huei, AU - Wu,Yu-Heng, AU - Shen,Rou-Chen, AU - Wu,Ching-Yuan, Y1 - 2021/08/05/ PY - 2021/05/15/received PY - 2021/07/17/revised PY - 2021/08/03/accepted PY - 2021/8/14/pubmed PY - 2021/9/29/medline PY - 2021/8/13/entrez KW - (+)-Catechin (Pubchem CID: 9064) KW - Beta variant KW - Epsilon variant KW - GB-2 KW - SARS-CoV-2 KW - Spike protein KW - Theaflavin (Pubchem CID: 135403798) KW - Theaflavin 3-gallate (Pubchem CID: 136825044) SP - 112011 EP - 112011 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 142 N2 - Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 μg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/34388530/GB_2_blocking_the_interaction_between_ACE2_and_wild_type_and_mutation_of_spike_protein_of_SARS_CoV_2_ DB - PRIME DP - Unbound Medicine ER -