AI Article Synopsis
- Scientists are trying to find new medicines to treat COVID-19 because of fast-spreading variants like Omicron that can avoid antibodies.
- They created a special cell model to study how a protein called ACE2 helps the virus enter human cells and how to reduce ACE2 levels.
- The best results came from using two specific drugs together, which helped stop the virus from getting into certain human cells, suggesting a way to find new treatments for COVID-19.
Article Abstract
Because of rapid emergence and circulation of the SARS-CoV-2 variants, especially Omicron which shows increased transmissibility and resistant to antibodies, there is an urgent need to develop novel therapeutic drugs to treat COVID-19. In this study we developed an cellular model to explore the regulation of ACE2 expression and its correlation with ACE2-mediated viral entry. We examined ACE2 expression in a variety of human cell lines, some of which are commonly used to study SARS-CoV-2. Using the developed model, we identified a number of inhibitors which reduced ACE2 protein expression. The greatest reduction of ACE2 expression was observed when CK869, an inhibitor of the actin-related protein 2/3 (ARP2/3) complex, was combined with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an inhibitor of sodium-hydrogen exchangers (NHEs), after treatment for 24 h. Using pseudotyped lentivirus expressing the SARS-CoV-2 full-length spike protein, we found that ACE2-dependent viral entry was inhibited in CK869 + EIPA-treated Calu-3 and MDA-MB-468 cells. This study provides an model that can be used for the screening of novel therapeutic candidates that may be warranted for further pre-clinical and clinical studies on COVID-19 countermeasures.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733118 | PMC |
| http://dx.doi.org/10.1016/j.jve.2022.100307 | DOI Listing |
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