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

Abstract

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.