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

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.

Anti-Fungal Drug Anidulafungin Inhibits SARS-CoV-2 Spike-Induced Syncytia Formation by Targeting ACE2-Spike Protein Interaction

“…The MD simulation analysis also confirmed that the anidulafungin-ACE2 complex is stable, indicating that it can effectively block the ACE2 receptor sites by interacting with critical amino acid residues. Recently, an in-silico study has also shown that anidulafungin has an affinity toward ACE2 receptors (Ahsan and Sajib, 2021).…”

Insights into COVID-19: Perspectives on Drug Remedies and Host Cell Responses

“…Rational drug design strategies have been investigated during the COVID-19 pandemic [223]. This includes structural design of molecules that could bind to the spike protein [224] or ACE2 [225] to inhibit virus interaction with its cellular receptor. Additionally, molecules and nucleoside analogs that can bind to viral proteases and RdRp were reported [226,227].…”

Structure-Based Screening of Potential Drugs against SARS-CoV-2 Variants

“…Drug-repurposing of FDA-approved drugs is the fastest way to look for possible therapies against SARS-CoV-2 since they are already proven safe for use in human beings. Some researchers have done a virtual screening of FDA-approved drugs against the RBD of SARS-CoV-2 in hopes of finding a potential inhibitor to prevent viral entry into the host cells [26][27][28][29][30][31]. However, those studies focused on the wild-type SARS-CoV-2.…”