(Press-News.org) CHAPEL HILL, NC - Publishing their work in Nature, scientists at the UNC School of Medicine and UNC Gillings School of Global Public Health found that the orally administered experimental drug EIDD-2801 halts SARS-CoV-2 replication and prevents infection of human cells in a new in vivo lab model containing human lung tissue.
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 number of new COVID-19 cases continues to rise in many parts of the world, with the highest incidence in the United States. Although some highly efficacious vaccines have been authorized for emergency use, it may take considerable time to reach target vaccination levels needed for herd immunity due to the logistics of vaccine manufacturing, shipping, storage, and distribution as well as public acceptance.
Also, SARS-CoV-2 variants have emerged which appear to have increased transmissibility and have added more challenges to ensure vaccine viability. Therefore, 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.
Mouse models 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 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, but none of these models possess the diverse human cells found in human lungs where viral infection can cause severe disease. UNC scientists created a solution to this problem - 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 infection that recapitulates several features of early diffuse lung damage seen in COVID-19 patients. In addition, acute SARS-CoV-2 infection induced a robust and sustained Type I interferon and 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 25,000-fold reduction in the number of infectious particles in human lung tissue when treatment was initiated 24 hours post-exposure," said senior author J. Victor Garcia, PhD, professor of medicine and director of the International Center for the Advancement of Translational Science. "Virus titers were significantly reduced by 96% when treatment was started 48 hours post-exposure."
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 titers 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 and assistant director of the International Center for the Advancement of Translational Science.
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, PhD, 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, PhD, 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."
INFORMATION:
Clinical trials for EIDD-2801 are ongoing, and the first results could be released as early as March.
Other authors are Claire Johnson, Wenbo Yao, Martina Kovarova, Kenneth Dinnon III, Hongwei Liu, Victoria Madden, Halina Krzystek, Chandrav De, Kristen White, Kendra Gully, Alexandra Schäfer, Tanzila Zaman, Sarah Leist, Paul Grant, Frederic Askin, Edward Browne, Corbin Jones, and Raymond Pickles, all from UNC-Chapel Hill, and Gregory Bluemling, Alexander Kolykhaloy, Michael Natchus, George Painter from Emory University.
This work was supported through grants from the National Institutes of Health and the North Carolina Coronavirus Relief Fund.
A global survey of healthcare providers by the International Osteoporosis Foundation (IOF), the National Osteoporosis Foundation (NOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) has revealed unprecedented effects of the Covid-19 pandemic on worldwide healthcare delivery for osteoporosis.
Osteoporosis is a chronic, age-related disease which is associated with life-changing fragility fractures. Approximately 740,000 people lose their lives following hip fractures every year.
The survey report is based on online questionnaires completed from April to June 2020 by 209 healthcare providers in 53 countries: 28% from Europe, 24% from North America, and 19%, 17% and 12% from the Asia-Pacific, Middle ...
DALLAS - Feb. 8, 2021 - World health experts have long suspected that the incidence of COVID-19 has been higher than reported. Now, a machine-learning algorithm developed at UT Southwestern estimates that the number of COVID-19 cases in the U.S. since the pandemic began is nearly three times that of confirmed cases.
The algorithm, described in a study published today in PLOS ONE, provides daily updated estimates of total infections to date as well as how many people are currently infected across the U.S. and in 50 countries hardest hit by the pandemic.
As of Feb. 4, according to ...
As teens' use of social media has grown over the past decade, so too has the suicide rate among younger people, with suicide now being the second leading cause of death among those ages 10 to 34. Many have suggested that social media is driving the increased suicide risk, but because social media is still relatively new, it's been difficult to determine its long-term effects on mental health.
In the longest study to date on social media use and suicidality, BYU research recently published in the Journal of Youth and Adolescence now offers some answers.
Through ...
One of the dozens of unusual symptoms that have emerged in COVID-19 patients is a condition that's informally called "COVID brain" or "brain fog." It's characterized by confusion, headaches, and loss of short-term memory. In severe cases, it can lead to psychosis and even seizures. It usually emerges weeks after someone first becomes sick with COVID-19.
In the February 8, 2021, issue of the journal Cancer Cell, a multidisciplinary team from Memorial Sloan Kettering reports an underlying cause of COVID brain: the presence of inflammatory molecules in the liquid surrounding the brain and spinal cord (called the cerebrospinal fluid). The findings suggest that anti-inflammatory drugs, such as steroids, may ...
Exposure to sexual assault in the U.S. military doubled the odds that a service member would leave the military within 28 months, and sexual harassment was associated with roughly 8% of all military separations during this same time period, according to a new report from the RAND Corporation.
Specifically, the report estimates that sexual assaults were associated with 2,000 more separations than would normally be expected, and another 8,000 separations were associated with sexual harassment.
"Sexual assault and sexual harassment are associated with a wide range of harms to individual service members, but this study highlights another negative impact of these crimes - higher rates of attrition and associated harms to force readiness." said Andrew ...
The world is changing rapidly and in order to serve the human population dealing with those changes, American universities need to change, too. In fact, their role is to model the resiliency that all institutions need to embrace, according to Arizona State University President Michael M. Crow.
While many leading universities are poised to advance society and help respond to the challenges of disruptive change through their traditional role in education and discovery, many face a number of barriers that make them less prepared to respond to the rapidly changing conditions and the demands they create.
What is emerging is a new type of university, one that steps beyond the American research university model and ...
Not all friendships are created equal. Some friends get along; others struggle to avoid conflict. Conventional wisdom holds that the tenor of a friendship with someone who is nice differs from that with someone who is mean, such that the former discourages negative interactions whereas the latter aggravates them. Although it is logical to assume that children who are mean have friendships characterized by growing strife and that children who are nice report little of the same, these assumptions have not yet been tested in the real-world friendships of children.
Researchers from Florida Atlantic University's Charles E. Schmidt College of Science are the first to conduct a longitudinal study to examine the extent to which being "nice" (prosocial behavior) and being "mean" (relationally aggressive ...
A new study from University of Alberta researchers has shown that traumatic or stressful events in childhood may lead to tiny changes in key brain structures that can now be identified decades later.
The study is the first to show that trauma or maltreatment during a child's early years--a well-known risk factor for developing mental health conditions such as major depressive disorder in adulthood--triggers changes in specific subregions of the amygdala and the hippocampus.
Once these changes occur, researchers believe the affected regions of the brain may not function as well, potentially increasing the risk of developing mental health disorders as adults during times of stress.
"Now ...
CORVALLIS, Ore. - Marching band members in leadership roles are more likely to feel discomfort in the neck and upper back than their less experienced bandmates, who in turn are more susceptible to left-hand pain and cognitive strain, a new study by Oregon State University suggests.
The findings also showed that gender had no bearing on how much discomfort a musician felt or the band member's perception of workload.
"The study really seems to indicate that a player's level of experience and role within the band are what drive how much discomfort they feel," said industrial ...
Neurons are the primary cells of the nervous system, and the signals that are transmitted between them are responsible for all our actions and our cognitive ability. In particular, learning and memory are believed to be associated with a process called "long-term potentiation," which is the strengthening of connections between specific neurons via continued signal transmission through "synapses" (small gaps between neurons). Long-term potentiation can change the connection between neurons via synapses--by changing their size and composition. Understanding ...
