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primary topic: Chemically synthesized LRAD3-D1 interacts with N-terminal domain of SARS-CoV-2 spike protein

Chemically synthesized LRAD3-D1 interacts with N-terminal domain of SARS-CoV-2 spike protein
type: AcademicArticle
type: Article
abstract: Growing evidence of post-COVID neurological complications, such as encephalopathy, neurodegeneration, and cognitive impairment, suggests severe acute respiratory syndrome-related corona virus 2 (SARS-CoV-2) viral infection into the central nervous system (CNS). Therefore, understanding the mechanisms of viral entry into the CNS, where human angiotensin-converting enzyme 2 (ACE2) is barely expressed, is critical for addressing the neurological consequences of COVID-19. Importantly, the low-density lipoprotein receptor class A domain containing 3 (LRAD3) is overexpressed in brain cells, suggesting a possible ACE2-independent alternate pathway of viral entry into brain cells. Herein, the interaction of the chemically synthesized LRAD3 domains with SARS-CoV-2 spike protein is reported. It is observed that the extracellular domains of LRAD3 depend on calcium for proper folding and maintaining their structural integrity. The results reveal that domain 1 of LRAD3, which is most accessible from the cell surface, engages with the N-terminal domain of the viral spike protein. These findings open up possibilities to develop new therapeutic strategies targeting ACE2 independent viral entry pathways.
date: 2025-11
volume: 26
issue: 22
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

Wiley
type: Organization

Chembiochem
type: Collection

Arighna Sarkar
type: Person
given name: Arighna
family name: Sarkar

Sreejith Raran-Kurussi
type: Person
given name: Sreejith
family name: Raran-Kurussi

Rathina Delipan
type: Person
given name: Rathina
family name: Delipan

Mrinmoy Jana
type: Person
given name: Mrinmoy
family name: Jana

Kalyaneswar Mandal
type: Person
given name: Kalyaneswar
family name: Mandal

Rajesh P Ringe
type: Person
given name: Rajesh P
family name: Ringe

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primary topic: Chemically synthesized LRAD3-D1 interacts with N-terminal domain of SARS-CoV-2 spike protein