Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Repurposing of Approved Drugs with Potential to Interact with SARS-CoV-2 Receptor

Version 1 : Received: 19 April 2020 / Approved: 20 April 2020 / Online: 20 April 2020 (16:01:29 CEST)
Version 2 : Received: 30 July 2020 / Approved: 2 August 2020 / Online: 2 August 2020 (09:23:18 CEST)

How to cite: Sajib, A. Repurposing of Approved Drugs with Potential to Interact with SARS-CoV-2 Receptor. Preprints 2020, 2020040369 (doi: 10.20944/preprints202004.0369.v2). Sajib, A. Repurposing of Approved Drugs with Potential to Interact with SARS-CoV-2 Receptor. Preprints 2020, 2020040369 (doi: 10.20944/preprints202004.0369.v2).

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, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease (COVID-19).

Subject Areas

COVID-19; SARS-CoV-2; spike protein; ACE1; ACE2; host-virus interaction; drug repurposing

Comments (1)

Comment 1
Received: 2 August 2020
Commenter: Abu Sajib
Commenter's Conflict of Interests: Author
Comment: This updated version of the manuscript contains addional information and a more detailed discussion section.
+ Respond to this comment

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 1
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.