We have now performed experiments in HT29 and HepG2 cells to test mitigation/synthetic lethality between…
Like so many people around the world, the 12 members of our lab have been following the global spread of the SARS-CoV2 coronavirus pandemic and wondering whether we can help out in any way. None of us are doctors. The science we think about on a daily basis (using high-throughput genomic techniques such as CRISPR screening to understand and develop therapies for genetic disease) doesn’t concern infectious disease or the body’s responses to it. Is there something, however modest, that we can do that may help others figure out how best to treat COVID-19 patients?
To be honest, we’re not sure. But we have come up with a few areas where we think the tools of genomics and gene editing might provide insight that could come in handy to those on the front lines treating COVID-19 patients. We have begun efforts in a few different areas where we think the rapid collection of genomic datasets may have a non-zero chance of informing the medical community.
Specifically, we see a possible area of need in understanding how two current front-line COVID-19 drugs, remdesivir and hydroxychloroquine, interact with human genes to cause toxicity. These two drugs have been repurposed from other disease indications (remdesivir was designed to target Ebola RNA-dependent RNA polymerase or RdRP, hydroxychloroquine is predominantly used as an anti-malarial with an unclear mechanism) and are now being dosed to thousands of patients across the world in accelerated clinical trial settings.
They are bound to cause toxicity to patients due to interactions with human genes. By understanding how they do so, maybe we can help to identify drugs or nutrients to alleviate this toxicity in patients being dosed with these primary drugs. Maybe we can identify genetic predispositions or pre-existing conditions that should disqualify patients from being diagnosed with these drugs.
Treatment with these drugs is also likely to induce viral mutations that impart drug resistance to the virus. Can we build assays to understand how SARS-CoV2 might develop such resistance, which could inform what to do if such resistant strains emerge?
These are the ideas we have at the moment. We expect our thinking to change, our plans to change. Given the lightning fast spread of COVID-19 and the equally fast pace of the global response, we will provide real-time updates on the science we are doing, the issues we face as we move forward, and the questions we have been mulling over as we consider how we as scientists and as concerned human beings should respond to this health crisis both on this website and on our Twitter feed (@SherwoodLab). Please feel free to get in touch through Twitter or email (email@example.com) with questions or feedback.