Repurposing of approved drugs with potential to interact with SARS-CoV-2 receptor

Tamim Ahsana, Abu Ashfaqur Sajib

10.1016/j.bbrep.2021.100982

Research curated

Abstract

Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1 and potentially interfere with the entry of SARS-CoV-2 inside the host cells.

Source: PMC

Related molecules

Name	Synonyms	Genes
Angiotensin Converting Enzyme	ACE1,ACE
Avatrombopag
Natamycin
Pibrentasvir
Posaconazole
Reserpine
Amphotericin B
Azithromycin	homoerythromycin A, Azithramycine, Azithromycin (TN), Azasite (TN), Azithromycin (INN)
Deslanoside
Eptifibatide
Nystatin
Rifamycin	Rifocin
Vancomycin
Alatrofloxacin
Azilsartan kamedoxomil
Baloxavir Marboxil
Betrixaban
Butenafine
Candicidin
Celecoxib
Deserpidine
Dihydroergotoxine
Doravirine
Loperamide
Loratadine
Lusutrombopag
Maraviroc
Saralasin
Zafirlukast
Ceruletide
Simvastatin
Nelfinavir
Sirolimus
Dihydroergotamine
Angiotensin-converting enzyme 2	ACE-related carboxypeptidase, ACE2	ACE2
Digitoxin
Digoxin
Rifaximin
Mefloquine
Rifapentine
Cefoperazone
Pitavastatin
Icatibant
Indinavir
Anidulafungin

Related interactions

Target	Drug	Type	Result
Angiotensin Converting Enzyme	Avatrombopag	Computational	positive
Angiotensin-converting enzyme 2	Avatrombopag	Computational	positive
Angiotensin Converting Enzyme	Ceruletide	Computational	positive
Angiotensin-converting enzyme 2	Ceruletide	Computational	positive
Angiotensin Converting Enzyme	Natamycin	Computational	positive
Angiotensin-converting enzyme 2	Natamycin	Computational	positive
Angiotensin Converting Enzyme	Pibrentasvir	Computational	positive
Angiotensin-converting enzyme 2	Pibrentasvir	Computational	positive
Angiotensin Converting Enzyme	Posaconazole	Computational	positive
Angiotensin-converting enzyme 2	Posaconazole	Computational	positive
Angiotensin Converting Enzyme	Reserpine	Computational	positive
Angiotensin-converting enzyme 2	Reserpine	Computational	positive
Angiotensin Converting Enzyme	Rifapentine	Computational	positive
Angiotensin-converting enzyme 2	Rifapentine	Computational	positive
Angiotensin Converting Enzyme	Amphotericin B	Computational	positive
Angiotensin-converting enzyme 2	Amphotericin B	Computational	positive
Angiotensin Converting Enzyme	Anidulafungin	Computational	positive
Angiotensin Converting Enzyme	Azithromycin	Computational	positive
Angiotensin-converting enzyme 2	Azithromycin	Computational	positive
Angiotensin Converting Enzyme	Deslanoside	Computational	positive
Angiotensin-converting enzyme 2	Deslanoside	Computational	positive
Angiotensin Converting Enzyme	Digitoxin	Computational	positive
Angiotensin-converting enzyme 2	Digoxin	Computational	positive
Angiotensin Converting Enzyme	Eptifibatide	Computational	positive
Angiotensin-converting enzyme 2	Eptifibatide	Computational	positive
Angiotensin Converting Enzyme	Icatibant	Computational	positive
Angiotensin-converting enzyme 2	Icatibant	Computational	positive
Angiotensin Converting Enzyme	Nystatin	Computational	positive
Angiotensin-converting enzyme 2	Nystatin	Computational	positive
Angiotensin Converting Enzyme	Rifamycin	Computational	positive
Angiotensin-converting enzyme 2	Rifamycin	Computational	positive
Angiotensin Converting Enzyme	Sirolimus	Computational	positive
Angiotensin-converting enzyme 2	Sirolimus	Computational	positive
Angiotensin Converting Enzyme	Vancomycin	Computational	positive
Angiotensin-converting enzyme 2	Vancomycin	Computational	positive
Angiotensin Converting Enzyme	Alatrofloxacin	Computational	positive
Angiotensin-converting enzyme 2	Alatrofloxacin	Computational	positive
Angiotensin Converting Enzyme	Azilsartan kamedoxomil	Computational	positive
Angiotensin-converting enzyme 2	Azilsartan kamedoxomil	Computational	positive
Angiotensin Converting Enzyme	Baloxavir Marboxil	Computational	positive
Angiotensin-converting enzyme 2	Baloxavir Marboxil	Computational	positive
Angiotensin Converting Enzyme	Betrixaban	Computational	positive
Angiotensin-converting enzyme 2	Betrixaban	Computational	positive
Angiotensin Converting Enzyme	Butenafine	Computational	positive
Angiotensin-converting enzyme 2	Butenafine	Computational	positive
Angiotensin Converting Enzyme	Candicidin	Computational	positive
Angiotensin-converting enzyme 2	Candicidin	Computational	positive
Angiotensin Converting Enzyme	Cefoperazone	Computational	positive
Angiotensin-converting enzyme 2	Cefoperazone	Computational	positive
Angiotensin Converting Enzyme	Celecoxib	Computational	positive
Angiotensin-converting enzyme 2	Celecoxib	Computational	positive
Angiotensin Converting Enzyme	Deserpidine	Computational	positive
Angiotensin-converting enzyme 2	Deserpidine	Computational	positive
Angiotensin Converting Enzyme	Dihydroergotoxine	Computational	positive
Angiotensin-converting enzyme 2	Dihydroergotamine	Computational	positive
Angiotensin Converting Enzyme	Doravirine	Computational	positive
Angiotensin-converting enzyme 2	Doravirine	Computational	positive
Angiotensin Converting Enzyme	Indinavir	Computational	positive
Angiotensin Converting Enzyme	Loratadine	Computational	positive
Angiotensin-converting enzyme 2	Loratadine	Computational	positive
Angiotensin Converting Enzyme	Lusutrombopag	Computational	positive
Angiotensin-converting enzyme 2	Lusutrombopag	Computational	positive
Angiotensin Converting Enzyme	Maraviroc	Computational	positive
Angiotensin-converting enzyme 2	Maraviroc	Computational	positive
Angiotensin Converting Enzyme	Mefloquine	Computational	positive
Angiotensin-converting enzyme 2	Mefloquine	Computational	positive
Angiotensin Converting Enzyme	Nelfinavir	Computational	positive
Angiotensin Converting Enzyme	Pitavastatin	Computational	positive
Angiotensin-converting enzyme 2	Pitavastatin	Computational	positive
Angiotensin Converting Enzyme	Saralasin	Computational	positive
Angiotensin-converting enzyme 2	Saralasin	Computational	positive
Angiotensin Converting Enzyme	Simvastatin	Computational	positive
Angiotensin-converting enzyme 2	Simvastatin	Computational	positive
Angiotensin Converting Enzyme	Zafirlukast	Computational	positive
Angiotensin-converting enzyme 2	Zafirlukast	Computational	positive
Angiotensin-converting enzyme 2	Nelfinavir	Computational	positive
Angiotensin Converting Enzyme	Rifaximin	Computational	positive
Angiotensin-converting enzyme 2	Rifaximin	Computational	positive
Angiotensin-converting enzyme 2	Indinavir	Computational	positive
Angiotensin-converting enzyme 2	Anidulafungin	Computational	positive