Analyses identifying more than 300 protein interactions involved in infections with SARS-CoV-2, of which around one-fifth serve as targets for existing drugs, are reported in Nature today. Some of the drugs that can act on these proteins are shown in the study to have antiviral action in laboratory tests. These findings suggest that there may be potential for developing treatments for COVID-19 by repurposing drugs that are already approved or under investigation for other conditions.
Efforts to develop vaccines against or treatments for SARS-CoV-2 infection have been hampered by a limited understanding of how this coronavirus hijacks the human host. To address this issue, Nevan Krogan and colleagues investigate how 26 of the 29 SARS-CoV-2 proteins interact with human proteins. The authors identify 332 notable interactions, among which 66 human proteins are found to be targeted by 69 known compounds, including 29 FDA-approved drugs and 40 compounds in clinical or preclinical trials. They went on to test a subset of these agents to identify two groups that had antiviral activity in laboratory experiments, although no tests were performed in individuals with SARS-CoV-2. The antiviral agents blocked protein translation (a key process for viral replication) or targeted specific receptors (Sigma1 and Sigma2) to disrupt the virus.
The insights into the mechanisms of SARS-CoV-2 infection in humans and the identification of drugable targets have the potential to guide new therapeutic avenues for the treatment of COVID-19. However, the authors emphasize that caution is needed when considering the use of known drugs for this purpose, as there may be unwanted side effects. Drugs that interact with Sigma1 and Sigma2 receptors may also have proviral activity, for example. Further study of the agents shown to target SARS-CoV-2 infection-related proteins is warranted.
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