In response to the COVID-19 pandemic, Gladstone scientists have rapidly pivoted the focus of their research labs to the novel virus, SARS-CoV-2. Specifically, they are leveraging their established tools, unique infrastructure, and diverse expertise in virology to develop improved diagnostics, identify targeted treatment strategies, and invent preventative approaches.
Gladstone scientists were instrumental in converting HIV/AIDS from a uniformly lethal disease into a chronic condition, and are now bringing the same urgency and focus to combatting COVID-19 in a comprehensive manner.
Image Credit: Novel Coronavirus SARS-CoV-2 by NIAID is licensed under CC BY 2.0
How Gladstone Is Contributing
Gladstone scientists are collaborating to develop a CRISPR-based method to rapidly measure COVID-19 RNA. By combining the technique with smartphone technology, they aim to develop a diagnostic that could deliver rapid results and be widely deployed even far from traditional labs, such as in airports and other ports of entry, and in remote communities throughout the world. Another team is applying machine learning to discover biomarkers that will predict which patients are most likely to experience severe disease, and which may have an asymptomatic course.
Gladstone researchers mapped interactions between human host cell proteins and the virus, and are now using this information to identify therapeutic targets. Others are screening libraries of FDA-approved drugs and testing their effects on the virus in human lung “organoids” and human heart cells. Additional projects include investigating how the virus affects the brain, leading to cerebrovascular complications and stroke, and studying ways to rejuvenate the immune system to improve its ability to fight infection.
A Gladstone team is investigating the potential of an innovative alternative to a vaccine. Therapeutic interfering particles (TIPs) could turn the tables on the virus by hijacking its machinery to transform virus-infected cells into factories that produce more therapeutic particles than virus, slowing its spread.
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Current Research Projects
The Gladstone building is currently equipped with two BSL-3 labs, both of which will require ongoing upgrades to meet COVID-19 research demands. Such facilities are of incalculable value. Whatever breakthroughs and discoveries will lead us to overcome the current crisis, they are likely to originate in a BSL-3 lab.
Melanie Ott and Jennifer Doudna are collaborating to develop a CRISPR-based COVID-19 diagnostic assay as a viable alternative to conventional methods and a potential point-of-care test. The advantage of the assay is that it can be performed in a single step, is faster than current PCR-based assays (under 30 min), and, when combined with the right read-out technology, can be deployed outside the lab.
Protein Mapping for Drug Targets
Nevan Krogan and a large team of collaborators, including Melanie Ott, have mapped all the proteins the virus interacts with to hijack the human host cell’s machinery. These proteins serve as potential targets for drug therapies. The team is testing existing drugs targeting these interaction points to find those that may block infection. Learn more about this project.
Stopping Viral Entry
Warner Green’s lab is repurposing a world’s-first assay that was invented at Gladstone Institutes for research on HIV, to detect SARS-CoV-2 viral entry. Next, the lab will screen a carefully curated library of 12,000 existing FDA-approved and clinically safe drugs to identify any that effectively prevents the virus from entering host cells. We are also working to identify peptides that interfere with human proteins to prevent viral entry or fusion to host cells. Learn more about this project.
Gladstone is home to state-of-the-art models of human disease, called organoids, which mimic many features of the organs found in the body. Using cutting-edge technology, Melanie Ott and Todd McDevitt are creating “lungs in a dish” from human induced pluripotent stem cells to discover how the SARS-CoV-2 virus damages lung tissue. Learn more about this project.
Implications for the Heart
We are studying new ways to prevent COVID-19-induced heart damage, reduce mortality, and improve treatment outcomes. Buce Conklin, Todd McDevitt, and Melanie Ott are deploying cutting-edge stem cell technology and using cardiac microtissues to examine how the virus interacts with the heart. Learn more about this project.
Predictors of Recovery
The labs of Nadia Roan and Warner Greene are studying how immune responses in patients may help or hinder COVID-19 pathology. This includes determining correlations between immune system features and clinical outcomes, using natural immunity to inform vaccine development, and harnessing effective immunity for therapeutics. Learn more about this project.
Improving Immune Function with Stem Cells
We are investigating the idea that immune imbalance plays an important role in COVID-19. This imbalance is exacerbated in older individuals, making the virus especially difficult for an aged immune system to fight. In collaboration with the lab of Melanie Ott, Todd McDevitt and his team are working on an innovative strategy that uses treatment with pluripotent stem cells to correct this imbalance and reduce the severity of disease in aged individuals.
COVID-19 and the Brain
Some COVID-19 patients show neurologic signs in addition to respiratory symptoms. Emerging studies suggest COVID-19 pathology results in part from an excessive response of the body’s immune system. This immune response also affects the brain, and the labs of Katerina Akassoglou and Warner Greene are working to understand how combined with the virus it contributes to brain pathology in COVID-19 patients.
Using AI to Predict the Clinical Course of COVID-19
Using breakthrough technology platforms, we aim to identify biomarkers, biological molecules that correlate with disease outcomes and can be used to predict the clinical course of COVID-19. Katie Pollard and her team are deploying artificial intelligence and machine learning to analyze the massive datasets generated by this project and define biomarkers that will help physicians design informed and well stratified care for COVID-19. Learn more about this research project.
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How Does the Coronavirus Spread?
Coronaviruses are a large family of viruses that predominantly circulate in bats. They occasionally transmit from bats to other animals, and then to people. The virus responsible for the current outbreak, now called SARS-CoV-2, is thought to primarily spread from person-to-person through respiratory droplets, which are created when a person coughs or sneezes.
What Are the Symptoms of Infection, and When Should People Seek Medical Advice?
The most common symptoms are fever, cough, and shortness of breath. Most people will recover on their own by keeping their fever under control, using a room humidifier, staying well-hydrated, and basically staying home to rest. If symptoms become worse or concerning, call your health care provider.
How Long Can the Coronavirus Survive on Various Surfaces?
Recent studies, published but not yet peer-reviewed, indicate that the coronavirus can survive on plastic and stainless steel for up to 2 to 3 days, on cardboard for 24 hours, and on copper for 4 hours. That means you should consider every doorknob potentially contaminated. Bottom line: Keep your hands away from your face and wash your hands frequently, decontaminate your workspace, your computer and keyboard, your phone, and figure out a good way to open doors that reduces your chances of contaminating your hands.
How Does Testing Work and Who Can Administer the Test?
The test looks for the virus itself, not for antibodies against the virus. It is based on nasal swabs or pharyngeal (throat) swabs, which according to Chinese studies, is where there is the highest amount of virus. At first, all testing was centralized at the CDC, which is why it took so long for testing to become widespread. Now the CDC has allowed more laboratories, including from the private sector, and companies to carry out the test. UCSF has developed a test for clinical use but capacity is limited. However, the numbers will increase, and testing will be more and more available. Currently, as testing is still limited, a doctor has to approve it—for instance for people with clear symptoms or people who have been in close contact with an infected person.
Are There Extra Precautions One Should Take If Pregnant?
As far as we know today, there is no known risk to the fetus if the mother is affected with COVID-19, at least in the late stages of the pregnancy, so this is very different from other illnesses like the Zika virus infection. But it is clear that pregnant women have a somewhat weakened immune system, so if you are pregnant, you are generally more susceptible to infection (by any virus), and extra precautions should be taken. You should practice social distancing, and all the hygiene recommendations that are in place should be taken very seriously. Find out more about higher-risk populations.
“Gladstone is perfectly positioned to respond to the current coronavirus pandemic. Our scientists are working together to pivot their research to address this major public health crisis.”
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