The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19. 2021

Iqrar Ahmad, and Rahul Pawara, and Sanjay Surana, and Harun Patel
Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur (Dhule), Maharashtra, 425405, India.

The highly infectious disease COVID-19 is induced by SARS-coronavirus 2 (SARS-CoV-2), which has spread rapidly around the globe and was announced as a pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 binds to the host cell's angiotensin converting enzyme 2 (ACE2) receptor through the viral surface spike glycoprotein (S-protein). ACE2 is expressed in the oral mucosa and can therefore constitute an essential route for entry of SARS-CoV-2 into hosts through the tongue and lung epithelial cells. At present, no effective treatments for SARS-CoV-2 are yet in place. Blocking entry of the virus by inhibiting ACE2 is more advantageous than inhibiting the subsequent stages of the SARS-CoV-2 life cycle. Based on current published evidence, we have summarized the different in silico based studies and repurposing of anti-viral drugs to target ACE2, SARS-CoV-2 S-Protein: ACE2 and SARS-CoV-2 S-RBD: ACE2. This review will be useful to researchers looking to effectively recognize and deal with SARS-CoV-2, and in the development of repurposed ACE2 inhibitors against COVID-19.

UI MeSH Term Description Entries
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
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
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D053586 Virus Internalization The entering of cells by viruses following VIRUS ATTACHMENT. This is achieved by ENDOCYTOSIS, by translocation of the whole virus across the cell membrane, by direct MEMBRANE FUSION of the viral membrane with the CELL MEMBRANE, or by fusion of the membrane of infected cells with the membrane of non-infected cells causing SYNCYTIA to be formed. Viral Entry,Viral Internalization,Viral Membrane Fusion,Virus Entry,Virus Membrane Fusion,Entry, Viral,Entry, Virus,Fusion, Viral Membrane,Internalization, Viral,Internalization, Virus,Membrane Fusion, Viral
D058492 Drug Repositioning The deliberate and methodical practice of finding new applications for existing drugs. Drug Repurposing,Drug Rescue,Repositioning, Drug,Repurposing, Drug,Rescue, Drug

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