Abstract
COVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, therapeutics that can help manage the disease are still required until immunity has been achieved globally. The identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARS-CoV-2-ΔOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were particularly effective in supporting SARS-CoV-2 replication, which is in-line with reported proteinuria and liver damage in patients with COVID-19. Using the nano-luciferase as a measure of virus replication we identified 35 drugs that reduced replication in Vero cells and human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3 to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected cells. In conclusion, our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID.
Highlights
IntroductionThe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is having a widespread impact on global health with substantial loss of life
Using a nano-luciferase tagged version of the virus (SARS-CoV-2-ΔOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 Food and Drug Administration (FDA)-approved drugs
Hepatocytes, kidney glomerulus, and proximal tubule cells were effective in supporting SARS-CoV-2 replication, which is in-line with reported proteinuria and liver damage in patients with COVID-19
Summary
The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is having a widespread impact on global health with substantial loss of life. An early step in the infection process is interaction of the Spike protein on the surface of the virus with angiotensin-converting enzyme 2 (ACE2) on the surface of the host cell [5]. Using this information, first-generation vaccines have been generated against the Spike protein. The different stages of the disease, from the initial infection of host cells through to virus replication and the response (normal or extreme) of the immune system, offer opportunities to identify drugs, treatments, and therapies to help stop disease progression. The identification of safe and distributed medications that can target the different stages of virus infection and replication, could reduce the spread of SARS-CoV-2 and reduce the cases of COVID-19
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