When Richard Sherwood, PhD, convened his lab for a virtual meeting to discuss how their research would continue during the COVID-19 pandemic, one question predominated the conversation: How can we help?
Sherwood runs a genetics lab that uses the tools of genomics to understand and develop therapies for genetic disease. He is quick to acknowledge that the lab’s focus usually isn’t on viruses or how the body responds to them.
“We thought, is there something, however modest, that we can do that may help others figure out how best to treat COVID-19 patients?” he said. “We believe that research has a role to play, and we wanted to find a way to contribute.”
Drawing on their unique expertise, Sherwood’s 12-person team has found multiple ways that they can shed light on new, potential treatments being evaluated in the fight against COVID-19.
Examining Experimental Treatments for COVID-19
There are no approved therapies for treating patients infected with SARS-CoV-2 (the virus that causes COVID-19) but there are many experimental therapies that are being used as part of clinical research studies at the Brigham and elsewhere. Two of these drugs are hydroxychloroquine and remdesivir. Both drugs are known to have side effects but there is little information about how and why.
“For any drug, there are two important areas to consider: how it affects the virus and how it affects the person taking the drug. There are toxicity concerns for both hydroxychloroquine and remdesivir, and the interactions between these drugs and human proteins that mediate toxicity are not known,” said Sherwood.
That’s where the Sherwood lab comes in. In the lab, the team can expose cells to an experimental drug and then look on a genomic level to see which genes and pathways have been activated or deactivated in response to it. They can also do CRISPR screening — editing specific locations in the cells’ genomes to see which changes influence the toxic effects of a drug. These insights may help to identify drugs or nutrients to alleviate toxicity in patients being dosed with an experimental drug.
Precision Medicine for COVID-19
The team is also considering how the tools of genomics could be used to screen patient populations for genetic variants that may affect their response to SARS-CoV-2 infection or antiviral drug treatment.
“There may be specific population who respond better or poorly to a drug — ideally, we’d be able to predict this so that we can get the most effective drug to a patient in need as quickly as possible,” said Sherwood.
The team is also developing assays to assess how SARS-CoV-2 might develop resistance to antiviral therapies in the hopes of mitigating such drug resistance.
“These are the ideas we have at the moment. We expect our thinking to change, our plans to change,” the lab writes on its blog, where they have been providing real-time updates on the work they are doing. By sharing openly, they hope to help others move projects forward.
“Researchers around the world are putting their window of expertise to work on this problem,” said Sherwood. “If we can get our insights out to the right community, someone, somewhere may able to use this in conjunction with other research or clinical expertise. We hope that every little bit helps.”