Evidence supporting the use of peptides and peptidomimetics as potential SARS-CoV-2 (COVID-19) therapeutics. 2020

Sonya VanPatten, and Mingzhu He, and Ahmad Altiti, and Kai F Cheng, and Mustafa H Ghanem, and Yousef Al-Abed
Center for Molecular Innovation, Feinstein Institute of Bioelectronic Medicine Feinstein Institutes for Medical Research, Northwell Health 350 Community Drive, Manhasset, NY 11030, USA.

During a disease outbreak/pandemic situation such as COVID-19, researchers are in a prime position to identify and develop peptide-based therapies, which could be more rapidly and cost-effectively advanced into a clinical setting. One drawback of natural peptide drugs, however, is their proteolytic instability; peptidomimetics can help to overcome this caveat. In this review, we summarize peptide and peptide-based therapeutics that target one main entry pathway of SARS-CoV-2, which involves the host ACE2 receptor and viral spike (S) protein interaction. Furthermore, we discuss the advantages of peptidomimetics and other potential targets that have been studied using peptide-based therapeutics for COVID-19.

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
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011024 Pneumonia, Viral Inflammation of the lung parenchyma that is caused by a viral infection. Pneumonias, Viral,Viral Pneumonia,Viral Pneumonias
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
D000086382 COVID-19 A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent. 2019 Novel Coronavirus Disease,2019 Novel Coronavirus Infection,2019-nCoV Disease,2019-nCoV Infection,COVID-19 Pandemic,COVID-19 Pandemics,COVID-19 Virus Disease,COVID-19 Virus Infection,Coronavirus Disease 2019,Coronavirus Disease-19,SARS Coronavirus 2 Infection,SARS-CoV-2 Infection,Severe Acute Respiratory Syndrome Coronavirus 2 Infection,COVID19,2019 nCoV Disease,2019 nCoV Infection,2019-nCoV Diseases,2019-nCoV Infections,COVID 19,COVID 19 Pandemic,COVID 19 Virus Disease,COVID 19 Virus Infection,COVID-19 Virus Diseases,COVID-19 Virus Infections,Coronavirus Disease 19,Disease 2019, Coronavirus,Disease, 2019-nCoV,Disease, COVID-19 Virus,Infection, 2019-nCoV,Infection, COVID-19 Virus,Infection, SARS-CoV-2,Pandemic, COVID-19,SARS CoV 2 Infection,SARS-CoV-2 Infections,Virus Disease, COVID-19,Virus Infection, COVID-19
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
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
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
D057786 Peptidomimetics Compounds that are designed to mimic the 3D structure of a natural peptide or protein. Peptidomimetic

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