While researching new drugs for Covid-19 caused by the SARS-CoV-2 virus, a team led by researchers at the University of California, San Francisco, has identified a new potential target for drugs that can prevent SARS-CoV-2 infection. The new target is a protein called BRD2. BRD2 regulates the ACE2 receptor to which the SARS-CoV-2 virus binds to enter the host cell. In their new study, published January 13 in the journal Nature Cell Biology, researchers discovered that inhibiting the production of the BRD2 protein prevents the virus from infecting various types of human cells.
“We knew brd2 regulates the secretion of other genes, including those that help tumors grow in some types of cancers,” Martin Kampmann, associate professor of Biochemistry and Biophysics and senior author of the study, said in a report posted on the university’s website at the same time as the study was published. Our discovery of how the protein regulates ACE2 means that potentially this protein can be manipulated to make it difficult for SARS-CoV-2 to infect the host cell.”
Unlike many proteins studied as potential targets for drugs against Covid-19, the BRD2 protein is produced not by the virus, but by human host cells. Currently, BRD2 and others linked to this protein are being investigated as targets for cancer drugs in clinical trials.
Researchers discovered that the BRD2 protein regulates the enzyme ACE2 while researching human host proteins that grow in a laboratory environment, including lungs, heart and nasal cavity cells (these are tissues that are particularly vulnerable to infection and long-term damage due to Covid-19) that are effective on the virus’s ability to bind to different cell types.
Scientists scanned 2,325 proteins that they believe could have an effect on Covid-19 infection by affecting the virus’s interaction with human cells. They found that existing drugs targeting the BRD2 protein can prevent Covid-19 infection of hamsters, as well as sensitive cell types. Kampmann said, “We were surprised to see that the suppression of BRD2 had almost the same effect as ACE2 itself in terms of preventing ACE2 production and infection with Covid-19.” Despite the study’s promising results, the researchers cautioned that this new study is just a first step, and that more work is needed to pinpoint the safety and effectiveness of a BRD2 or other newly identified targets. For example, the study team found that blocking brd2 production also inhibits interferon production, the main protein in the body’s inflammatory response. Kampmann said, “It is important to find out more about these possible side effects. We do not know whether this effect on the immune system will be harmful or beneficial for an infected patient and under what conditions this benefit and harm will occur.”
