Topoisomerase and P13K/mTOR Inhibitors Reduce Susceptibility to COVID-19

A recently published study revealed that topoisomerase and P13K/mTOR inhibitors could reduce the susceptibility to the SARS-CoV-2. The viral spike protein enters the human cell by engaging with ACE2, which is copiously expressed on airway epithelial cells. Once the virus is attached to the cell the spike protein is cleaved by the transmembrane protease serine 2 internalizing the virus. The study used the Library of Integrated Network-Based Cellular Signatures (LINCS) program and evaluated the gene expression patterns found in association with different drug exposures in LINCS for 1800 drugs.

Two drug classes revealed the highest reduction in ACE2 expression. Topoisomerase inhibitors were associated with the most considerable fall in the ACE2 expression, which was proportional to its dose. Drugs like camptothecin, taselisib could be used in reducing the susceptibility to the virus. The researchers also studied cancer patients receiving suchACE-2 suppressing drugs and found that the odds of testing positive for COVID-19 were 35% lower than with other anti-cancer medications. The study also evaluated other factors that reduced ACE2 expression. The odds of testing positive for COVI-19 were three times lower in blood cancer and two times lower if a person belonged to a non-white race.

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Ref link: https://www.medrxiv.org/content/10.1101/2020.09.02.20186783v1