creators_name: Jana, Mrinmoy
creators_name: Delipan, Rathina
creators_name: Sarkar, Arighna
creators_name: Raran-Kurussi, Sreejith
creators_name: Ringe, Rajesh P
creators_name: Mandal, Kalyaneswar
type: article
datestamp: 2026-02-01 14:20:31
lastmod: 2026-02-01 14:20:31
metadata_visibility: show
title: Chemically synthesized LRAD3-D1 interacts with N-terminal domain of SARS-CoV-2 spike protein
keywords: LRAD3 ectodomain; SARS-CoV-2 entry; neurological disorders; peptide synthesis
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
publication: Chembiochem
volume: 26
number: 22
publisher: Wiley
pagerange: e202500403
citation:   Jana, Mrinmoy and Delipan, Rathina and Sarkar, Arighna and Raran-Kurussi, Sreejith and Ringe, Rajesh P and Mandal, Kalyaneswar  (2025) Chemically synthesized LRAD3-D1 interacts with N-terminal domain of SARS-CoV-2 spike protein.  Chembiochem, 26 (22).  e202500403.