@article{open3224,
          volume = {26},
          number = {22},
           month = {November},
          author = {Mrinmoy Jana and Rathina Delipan and Arighna Sarkar and Sreejith Raran-Kurussi and Rajesh P Ringe and Kalyaneswar Mandal},
           title = {Chemically synthesized LRAD3-D1 interacts with N-terminal domain of SARS-CoV-2 spike protein},
       publisher = {Wiley},
            year = {2025},
         journal = {Chembiochem},
           pages = {e202500403},
        keywords = {LRAD3 ectodomain; SARS-CoV-2 entry; neurological disorders; peptide synthesis},
             url = {http://crdd.osdd.net/open/3224/},
        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.}
}