Molecular interactions between perlecan LG3 and the SARS‐CoV‐2 spike protein receptor binding domain

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has caused a global health crisis with significant clinical morbidity and mortality. While angiotensin‐converting enzyme 2 (ACE2) is the primary receptor for viral entry, other cell surface and extracellular matrix proteins may also bind t...

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Bibliographic Details
Published in:Protein science 2024-01, Vol.33 (1), p.e4843-n/a
Main Authors: Gressett, Timothy E., Hossen, Md Lokman, Talkington, Grant, Volic, Milla, Perez, Hugo, Tiwari, Purushottam B., Chapagain, Prem, Bix, Gregory
Format: Article
Language:English
Subjects:
ACE2
Angiotensin
Angiotensin-converting enzyme 2
Angiotensin-Converting Enzyme 2 - metabolism
Binding
Cell surface
Coronaviruses
COVID-19
Extracellular matrix
Global health
Heparan sulfate
heparan sulfate proteoglycan
Heparan sulfate proteoglycans
Heparan Sulfate Proteoglycans - metabolism
Humans
LG3
molecular dynamics
Molecular interactions
Molecular modelling
Morbidity
Pathophysiology
Perlecan
Protein Binding
Proteins
Proteoglycans
Public health
Receptors
SARS-CoV-2 - metabolism
SARS‐CoV‐2
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - chemistry
Spike protein
Surface plasmon resonance
Viral diseases
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Summary:Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has caused a global health crisis with significant clinical morbidity and mortality. While angiotensin‐converting enzyme 2 (ACE2) is the primary receptor for viral entry, other cell surface and extracellular matrix proteins may also bind to the viral receptor binding domain (RBD) within the SARS‐CoV‐2 spike protein. Recent studies have implicated heparan sulfate proteoglycans, specifically perlecan LG3, in facilitating SARS‐CoV‐2 binding to ACE2. However, the role of perlecan LG3 in SARS‐CoV‐2 pathophysiology is not well understood. In this study, we investigated the binding interactions between the SARS‐CoV‐2 spike protein RBD and perlecan LG3 through molecular modeling simulations and surface plasmon resonance (SPR) experiments. Our results indicate stable binding between LG3 and SARS‐CoV‐2 spike protein RBD, which may potentially enhance RBD‐ACE2 interactions. These findings shed light on the role of perlecan LG3 in SARS‐CoV‐2 infection and provide insight into SARS‐CoV‐2 pathophysiology and potential therapeutic strategy for COVID‐19.
ISSN:0961-8368
1469-896X
1469-896X
DOI:10.1002/pro.4843