Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
| Autor: | David A. Ostrov, Andrew P. Bluhm, Danmeng Li, Juveriya Qamar Khan, Megha Rohamare, Karthic Rajamanickam, Kalpana K. Bhanumathy, Jocelyne Lew, Darryl Falzarano, Franco J. Vizeacoumar, Joyce A. Wilson, Marco Mottinelli, Siva Rama Raju Kanumuri, Abhisheak Sharma, Christopher R. McCurdy, Michael H. Norris |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Pathogens, Vol 10, Iss 11, p 1514 (2021) |
| Druh dokumentu: | article |
| ISSN: | 10111514 2076-0817 |
| DOI: | 10.3390/pathogens10111514 |
| Popis: | (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. |
| Databáze: | Directory of Open Access Journals |
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