Receptor-Loaded Virion Endangers GPCR Signaling: Mechanistic Exploration of SARS-CoV-2 Infections and Pharmacological Implications.
Int J Mol Sci
; 22(20)2021 Oct 11.
Article
in English
| MEDLINE | ID: covidwho-1463714
ABSTRACT
SARS-CoV-2 exploits the respiratory tract epithelium including lungs as the primary entry point and reaches other organs through hematogenous expansion, consequently causing multiorgan injury. Viral E protein interacts with cell junction-associated proteins PALS1 or ZO-1 to gain massive penetration by disrupting the inter-epithelial barrier. Conversely, receptor-mediated viral invasion ensures limited but targeted infections in multiple organs. The ACE2 receptor represents the major virion loading site by virtue of its wide tissue distribution as demonstrated in highly susceptible lung, intestine, and kidney. In brain, NRP1 mediates viral endocytosis in a similar manner to ACE2. Prominently, PDZ interaction involves the entire viral loading process either outside or inside the host cells, whereas E, ACE2, and NRP1 provide the PDZ binding motif required for interacting with PDZ domain-containing proteins PALS1, ZO-1, and NHERF1, respectively. Hijacking NHERF1 and ß-arrestin by virion loading may impair specific sensory GPCR signalosome assembling and cause disordered cellular responses such as loss of smell and taste. PDZ interaction enhances SARS-CoV-2 invasion by supporting viral receptor membrane residence, implying that the disruption of these interactions could diminish SARS-CoV-2 infections and be another therapeutic strategy against COVID-19 along with antibody therapy. GPCR-targeted drugs are likely to alleviate pathogenic symptoms-associated with SARS-CoV-2 infection.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Receptors, G-Protein-Coupled
/
COVID-19
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Ijms222010963
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