Biomaterial Database

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2. 2022

Changzhi Li, and Hongjuan Zhou, and Lingling Guo, and Dehuan Xie, and Huiping He, and Hong Zhang, and Yixiu Liu, and Lixia Peng, and Lisheng Zheng, and Wenhua Lu, and Yan Mei, and Zhijie Liu, and Jie Huang, and Mingdian Wang, and Ditian Shu, and Liuyan Ding, and Yanhong Lang, and Feifei Luo, and Jing Wang, and Bijun Huang, and Peng Huang, and Song Gao, and Jindong Chen, and Chao-Nan Qian

State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.

The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

UI	MeSH Term	Description	Entries
D007703	Peptidyl-Dipeptidase A	A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-\|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020).	ACE1 Angiotensin-Converting Enzyme 1,ACE1 Protein,Angiotensin Converting Enzyme,Angiotensin Converting Enzyme 1,Antigens, CD143,CD143 Antigens,Dipeptidyl Carboxypeptidase I,Kininase II,Peptidase P,Angiotensin I-Converting Enzyme,Carboxycathepsin,Dipeptidyl Peptidase A,Kininase A,ACE1 Angiotensin Converting Enzyme 1,Angiotensin I Converting Enzyme,Carboxypeptidase I, Dipeptidyl,Peptidyl Dipeptidase A
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000085962	Angiotensin-Converting Enzyme 2	A transmembrane glycoprotein with an extracellular catalytic domain which functions as a carboxypeptidase. It cleaves a single C-terminal residue from a distinct range of substrates. The catalytic efficiency is 400-fold higher with ANGIOTENSIN II as a substrate than with ANGIOTENSIN I. Angiotensin-converting enzyme 2 is also is a functional receptor for the spike glycoprotein (SPIKE PROTEIN, CORONAVIRUS) of the CORONAVIRUSES SARS-COV, SARS-COV2, and HCOV-NL63.	ACE-Related Carboxypeptidase,ACE2 Angiotensin-Converting Enzyme Protein 2,ACE2 Enzyme,ACE2 Protein,Angiotensin Converting Enzyme 2,Angiotensin-Converting Enzyme-Related Carboxypeptidase,ACE Related Carboxypeptidase,ACE2 Angiotensin Converting Enzyme Protein 2,Angiotensin Converting Enzyme Related Carboxypeptidase,Carboxypeptidase, ACE-Related,Carboxypeptidase, Angiotensin-Converting Enzyme-Related
D000086402	SARS-CoV-2	A species of BETACORONAVIRUS causing atypical respiratory disease (COVID-19) in humans. The organism was first identified in 2019 in Wuhan, China. The natural host is the Chinese intermediate horseshoe bat, RHINOLOPHUS affinis.	2019 Novel Coronavirus,COVID-19 Virus,COVID19 Virus,Coronavirus Disease 2019 Virus,SARS Coronavirus 2,SARS-CoV-2 Virus,Severe Acute Respiratory Syndrome Coronavirus 2,Wuhan Coronavirus,Wuhan Seafood Market Pneumonia Virus,2019-nCoV,2019 Novel Coronaviruses,COVID 19 Virus,COVID-19 Viruses,COVID19 Viruses,Coronavirus 2, SARS,Coronavirus, 2019 Novel,Coronavirus, Wuhan,Novel Coronavirus, 2019,SARS CoV 2 Virus,SARS-CoV-2 Viruses,Virus, COVID-19,Virus, COVID19,Virus, SARS-CoV-2,Viruses, COVID19
D000093485	COVID-19 Drug Treatment	The use of DRUGS to treat COVID19 or its symptoms.	COVID-19 Drug Therapy,COVID19 Drug Therapy,COVID19 Drug Treatment,Coronavirus Disease 2019 Drug Treatment,Coronavirus Disease-19 Drug Treatment,COVID 19 Drug Therapy,COVID 19 Drug Treatment,COVID-19 Drug Therapies,COVID19 Drug Therapies,COVID19 Drug Treatments,Coronavirus Disease 19 Drug Treatment,Drug Therapy, COVID-19,Drug Therapy, COVID19,Therapy, COVID-19 Drug,Therapy, COVID19 Drug,Treatment, COVID-19 Drug
D013634	Tannins	Polyphenolic compounds with molecular weights of around 500-3000 daltons and containing enough hydroxyl groups (1-2 per 100 MW) for effective cross linking of other compounds (ASTRINGENTS). The two main types are HYDROLYZABLE TANNINS and CONDENSED TANNINS. Historically, the term has applied to many compounds and plant extracts able to render skin COLLAGEN impervious to degradation. The word tannin derives from the Celtic word for OAK TREE which was used for leather processing.	Tannin
D062105	Molecular Docking Simulation	A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.	Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking
D064370	Spike Glycoprotein, Coronavirus	A class I viral fusion protein that forms the characteristic spikes, or peplomers, found on the viral surface that mediate virus attachment, fusion, and entry into the host cell. During virus maturation, it is cleaved into two subunits: S1, which binds to receptors in the host cell, and S2, which mediates membrane fusion.	Spike Glycoprotein, Bovine Coronavirus,Spike Glycoproteins, Coronavirus,E2 Spike Glycoprotein, Coronavirus,Glycoprotein S, Coronavirus,Spike Glycoprotein S1, Coronavirus,Spike Protein S2, Coronavirus,Spike Protein, Coronavirus,Coronavirus Spike Glycoprotein,Coronavirus Spike Protein