GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2

Autor: Yu-Shih Lin, Chang Geng-He, Wu Ching-Yuan, Li-Hsin Shu, Cheng-Ming Hsu, Yao-Hsu Yang, Yu-Heng Wu, Ming-Shao Tsai, Yu-Huei Wu, Yu-Ching Cheng, Reming-Albert Yeh, Hung-Te Liu, Rou-Chen Shen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Conformational change
Lineage (genetic)
medicine.drug_class
RM1-950
Spike protein
medicine.disease_cause
Monoclonal antibody
Antiviral Agents
Antioxidants
Catechin
Article
RBD
receptor binding domain
Theaflavin 3-gallate (Pubchem CID: 136825044)
T3G
Theaflavin 3-gallate
Epsilon variant
Gallic Acid
Drug Discovery
medicine
Biflavonoids
Humans
Protein Interaction Domains and Motifs
GU
glycyrrhiza uralensis Fisch. ex DC
COVID-19
coronavirus disease 2019
Pharmacology
Infectivity
Medicine
East Asian Traditional
Mutation
biology
ACE2
angiotensin converting enzyme 2
SARS-CoV-2
The severe acute respiratory syndrome coronavirus 2
SARS-CoV-2
HEK 293 cells
Wild type
COVID-19
General Medicine
Theaflavin (Pubchem CID: 135403798)
Virology
Antibodies
Neutralizing
Beta variant
HEK293 Cells
Spike Glycoprotein
Coronavirus
biology.protein
Angiotensin-Converting Enzyme 2
(+)-Catechin (Pubchem CID: 9064)
GB-2
Therapeutics. Pharmacology
Antibody
Protein Binding
Zdroj: Biomedicine & Pharmacotherapy, Vol 142, Iss, Pp 112011-(2021)
Biomedicine & Pharmacotherapy
ISSN: 0753-3322
Popis: 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.
Graphical Abstract ga1
Databáze: OpenAIRE
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