COVID-19, caused by the coronavirus SARS-CoV-2, has caused a large number of deaths worldwide, including more than 100,000 deaths in the United States to date. Vaccines are being developed, but are still at least a year away from public use. Many clinical trials repurposing existing medications are underway, but whether they will work and how well they will work is uncertain. One drug, remdesivir, has shown modest activity against COVID-19, but it can only be given through an IV and therefore cannot be used outside of the hospital. Many groups are studying antibodies as a possible treatment for COVID-19, which are naturally made by the body to fight viral infections. It is possible to make antibodies in the laboratory as therapies to fight COVID-19. However, this raises several concerns: (1) The antibody may not work against future coronaviruses because antibodies are very specific and will likely only work against SARS-CoV-2, making us still susceptible to future coronavirus pandemics; and (2) antibodies may actually worsen COVID-19 infection in some people, in a process called “antibody-dependent enhancement.” Even in people who are not treated with antibodies as a therapy, their own naturally occurring antibodies made to fight COVID-19 may sometimes worsen their infection through this process. Therefore, it is important to develop a therapy against COVID-19 that will be broadly effective against many coronaviruses and that can mitigate antibody-dependent enhancement.

We are developing a therapy called DF-COV that addresses these concerns. DF-COV interferes with SARS-CoV-2’s ability to infect cells by blocking its entryway into the cell. We expect this to prevent COVID-19 infection. For people who already have COVID-19, we expect DF-COV to slow the infection, prevent worsening of the disease, and help them recover faster. DF-COV is similar to an antibody, but is expected to be effective against more coronaviruses, not only SARS-CoV-2. This is because many coronaviruses use the same entryway to infect cells, and DF-COV blocks this shared entryway. This is important because in the last 20 years, there have already been two severe outbreaks from coronaviruses: the SARS epidemic (caused by SARS-CoV virus) and the COVID-19 pandemic. In the coming decades, we may expect more coronaviruses to appear. It will be critical to have an already-made therapeutic ready to treat and protect against these new coronaviruses. Earlier, similar therapies to DF-COV have been tested in the laboratory and have successfully blocked both SARS-CoV and SARS-CoV-2 infections, but none of these drugs have the safety features of DF-COV.

In addition to treating the virus itself, we believe these unique safety features of DF-COV will allow it to reduce COVID-19 complications caused by antibody-dependent enhancement, a process whereby antibodies made by the body to fight viral infection may actually help the virus to infect immune cells, spread infection, and cause inflammation that can worsen the illness. This has been well established in dengue virus and some other viruses. There is also evidence that coronavirus infection might lead to this phenomenon. It might be one reason why some patients with COVID-19 experience much more severe disease and why the symptoms of some COVID-19 patients worsen in the second week of the infection. It may also be part of the underlying cause of severe lung disease in COVID-19. We have addressed the risk of antibody-dependent enhancement by turning off the part of the DF-COV molecule that could cause antibody-dependent enhancement. This should both prevent DF-COV from causing antibody-dependent enhancement itself and also interfere with antibody-dependent enhancement that may already be naturally occurring due to body’s response to COVID-19. In this way, we expect DF-COV to both safely treat COVID-19 and potentially prevent and treat severe lung disease.

We have designed DF-COV so that it can be given both as an injection or through an IV. Many potential therapies that are being studied, such as remdesivir, can only be given through an IV. This prevents their use outside of the hospital or as a preventative medication. DF-COV can be given as an injection, similar to an insulin shot. This enables it to be given to military service members, veterans, and civilians where they are stationed, where they live, or where they work. It could be used to treat people with milder cases of COVID-19, preventing the disease from worsening or spreading to others. It could also potentially be used as a preventative medication given to people who are at higher risk of getting COVID-19, such as healthcare workers, military service members on ships or in bases, veterans and older adults, and people with lowered immune systems.