Network proteins of angiotensin-converting enzyme 2 but not angiotensin-converting enzyme 2 itself are host cell receptors for SARS-Coronavirus-2 attachment
Files in This Item:
|SARS COV 2 cell entry mechanism with figures.pdf||1.91 MB||Adobe PDF||Download|
|Title:||Network proteins of angiotensin-converting enzyme 2 but not angiotensin-converting enzyme 2 itself are host cell receptors for SARS-Coronavirus-2 attachment||Authors:||Kumar, Arun H.S.||Permanent link:||http://hdl.handle.net/10197/11397||Date:||7-May-2020||Online since:||2020-06-23T12:16:36Z||Abstract:||Background: Coronaviruses causing severe acute respiratory syndrome (SARS-CoV) are known to enter the host cells by attaching to the membrane bound angiotensin-converting enzyme 2 (ACE2). Using molecular docking the efficiency of interaction between SARS-CoV-2 surface proteins and ACE2 network proteins was assessed.Materials and Methods: The ACE2 protein network was identified using the STRING database. The reported SARS-CoV-2 target proteins were searched in the protein data bank and uniport database. The protein-protein interactions were assessed by molecular docking using the Chimera software. The PubChem database was searched for known inhibitors of host cell receptors interacting with SARS-CoV-2 surface proteins. Molecular docking was performed to evaluate the binding efficacy of these compounds against the SARS-CoV-2 targets using AutoDock Vina and the docked protein-ligand complex were visualised using the Chimera and PyMOL software.Results: A low binding affinity was observed between SARS-CoV-2 spike proteins (protein S, M and 6YLA) and ACE2. Coronaviruses are also reported to bind to dipeptidyl peptidase 4 (DPP4), which is a network protein of ACE2. Network analysis showed five membrane proteins associated with ACE2. The ACE2 network proteins were assessed for their binding affinity with all known SARS-CoV-2 surface proteins. The SARS-CoV-2 surface proteins showed preferential binding to network proteins such as DPP4 and Meprin A alpha but not ACE2. The binding efficacy (affinity (-5.86 to -7.10 Kcal/mol), Ki (6.32 – 22.04 mM) and IC50 (12.63 – 113.71 mM) values) of DPP4 inhibitors (saxagliptin and sitagliptin) against SARS-CoV-2 surface proteins, was observed to be at a therapeutically feasible concentration to prevent SARS-CoV-2 attachment and entry into host cells.Conclusion: SARS-CoV-2 surface proteins has better interactions with DPP4 and Meprin A alpha host cells receptors rather than ACE2. DPP4 inhibitors (saxagliptin and sitagliptin) by binding with SARS-CoV-2 surface proteins may be helpful in preventing the virus entry into the host cells.||Funding Details:||University College Dublin||metadata.dc.description.othersponsorship:||Royal Society-UK
|Type of material:||Technical Report||Publisher:||Research Square||Keywords:||Host cell receptors; DPP4; Antiviral agents; SARS-CoV-2; COVID-19; Coronavirus||DOI:||10.21203/rs.3.rs-27149/v1||Language:||en||Status of Item:||Not peer reviewed|
|Appears in Collections:||Veterinary Medicine Research Collection|
Show full item record
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.