A team of scientists from the UNC School of Medicine and UNC Gillings School of Global Public Health just made a groundbreaking discovery. They found that an orally administered experimental drug called EIDD-2801 halts SARS-CoV-2 replication and prevents infection of human cells in a new in vivo lab model containing human lung tissue.
As you already know, “severe acute respiratory syndrome coronavirus 2” or SARS-CoV-2 for short, is the virus that causes COVID-19. The study was published on Feb. 9th of this year in the journal Nature. Separate phase 2 and 3 clinical trials are ongoing to evaluate EIDD-2801 safety in humans and its effect on viral shedding in COVID-19 patients. The first clinical trial results could be released as early as March.
Why Vaccines Aren’t Enough
The number of new COVID-19 cases continues to rise in many parts of the world, with the emergence of coronavirus variants. Although experimental vaccines have been authorized for emergency use, it may take considerable time to reach herd immunity due to vaccines being difficult to manufacture, transport, store, and distribute.
For these reasons, alternative treatments and preventive approaches that can be widely and rapidly implemented are urgently needed to curb the risk for COVID-19 related hospitalization and death in multiple settings including nursing homes and long-term care facilities.
The Difficult Study
Mouse models are often used for studies. They can be useful in studying highly pathogenic human coronaviruses including SARS-CoV-2 and compounds that might control infection. But human coronaviruses do not replicate in mice. That is, unless researchers alter the virus, genetically modify the mice, or introduce the individual human receptor genes into mice so the virus can infect cells.
Such mouse models have added to the scientific community’s understanding of coronavirus infection and disease progression. However, none of these models possess the diverse human cells found in human lungs where viral infection can cause severe disease. UNC scientists came up with a solution to this problem. They created a line of mice with human lung tissue that includes all the primary human cells infected when individuals fall ill with COVID-19.
Immune-deficient mice implanted with human lung tissue (LoM) allowed for replication of SARS-CoV-2, which resulted in an infection that replicates several early symptoms of lung damage seen in COVID-19 patients. In addition, acute SARS-CoV-2 infection induced a robust and sustained inflammatory cytokine/chemokine response.
To evaluate the therapeutic efficacy of EIDD-2801 for COVID-19, the researchers administered EIDD-2801 to LoM starting 24 hours or 48 hours post-SARS-CoV-2 exposure and every 12 hours thereafter.
“We found that EIDD-2801 had a remarkable effect on virus replication after only two days of treatment – a dramatic, more than the 25,000-fold reduction in the number of infectious particles in human lung tissue when treatment was initiated 24 hours post-exposure. Virus loads were significantly reduced by 96% when treatment was started 48 hours post-exposure,” said J. Victor Garcia, PhD, Study Senior Author and Professor of Medicine.
Next, the researchers tested the ability of EIDD-2801 to prevent SARS-CoV-2 infection by administering the drug 12 hours prior to SARS-CoV-2 exposure and every 12 hours thereafter.
“Remarkably, we found that EIDD-2801 pre-exposure prophylaxis significantly inhibited SARS-CoV-2 replication – reducing virus load in the human lung tissues of LoM by over 100,000 fold in two independent experiments,” said co-first author Angela Wahl, PhD, assistant professor of medicine.
Bats are the presumed source of SARS-CoV-2 and the highly pathogenic human coronaviruses SARS-CoV and MERS-CoV, all of which emerged into the human population within the past two decades.
“We show that LoM allow for the in vivo study of all recently emerged human coronaviruses in a single platform,” said co-first author Lisa Gralinski, Ph.D., assistant professor of epidemiology. “Our model allows researchers to directly compare infection between human coronaviruses and the effectiveness of potential preventative and therapeutic approaches.”
Gralinski, added, “We also show efficient replication of endogenous bat coronaviruses in LoM human lung tissue without the need for prior adaptation of the viruses, confirming that bats harbor viruses that are capable of directly infecting humans without the need for further adaptation.”
“Previously, we demonstrated that EIDD-2801 is also efficacious against SARS-CoV and MERS-CoV infection in vivo and in primary human airway epithelial cultures,” said Ralph Baric, Ph.D., the William Kenan Distinguished Professor of Epidemiology at the UNC Gillings School of Global Public Health and the UNC School of Medicine.
“Overall, these results indicate that EIDD-2801 may not only be efficacious in treating and preventing COVID-19, it could also prove to be highly effective against future coronavirus outbreaks as well.”