Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells.
Pathogens
; 10(11)2021 Nov 20.
Article
in English
| MEDLINE | ID: covidwho-1524103
ABSTRACT
(1) Background:
There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2)Methods:
In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3)Results:
Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4)Conclusions:
Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Topics:
Variants
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Pathogens10111514
Similar
MEDLINE
...
LILACS
LIS