Data Kits, Supercomputers, And Llamas: Bio-IT Community Leaves No Stone Unturned In COVID-19 Research
May 1, 2020 | New insights from the global bio-IT community show progress in fight against COVID-19. From new data kits and supercomputers to free sequencing and llama-related research, companies and universities are leaving no stone unturned as they combat the novel virus.
Literature Updates
An international team of scientists collaborating through the Human Cell Atlas (HCA) Lung Biological Network has identified the goblet and ciliated cells in the nose as the likely initial infection points for the COVID-19 coronavirus, which could help explain its high transmission rate. Cells in the eye and in the lining of the intestine also contain viral-entry proteins, suggesting other possible routes of infection, they report in Nature Medicine. Their study also predicts how a key entry protein is regulated with other immune system genes and reveals potential targets for the development of treatments to reduce transmission. Multiple HCA consortium datasets of single cell RNA sequencing, from more than 20 different tissues of non-infected people, were analyzed. The HCA consortium aims to create reference maps of all human cells to understand health and disease, and more than 1,600 people across 70 countries are involved in the community. The data is openly available to scientists worldwide. DOI: s41591-020-0868-6
Researchers from the University of Texas at Austin, the National Institutes of Health and Ghent University in Belgium report in Cell that they have discovered a potential avenue for a coronavirus treatment involving llamas. They linked two copies of a special kind of antibody produced by llamas to create a new antibody that binds tightly to the spike protein on the SARS-CoV-2 that allows the virus to break into host cells. Initial tests indicate the new antibody blocks viruses displaying the spike protein from infecting cells in culture. The team will next conduct preclinical studies in animals such as hamsters or nonhuman primates. The goal is to develop a treatment that would help people soon after infection with the virus, potentially delivered via an inhaler. A llama named Winter has been involved in this line of research since 2016, when two other coronaviruses (SARS-CoV-1 and MERS-CoV) were being studied. DOI: 10.1016/j.cell.2020.04.031
Severe cases of COVID-19 infection begin with a fluid problem, according to researchers at Radboud University Medical Center in The Netherlands. They report on an essential but overlooked mechanism in the disease process of COVID-19 in eLife. An international collaborative effort is now underway attempting to turn their insights into potential treatments. Excess fluid is a common denominator in all three phases of infection. The lungs initially fill up with fluid and patients become short of breath, which researchers theorize is due in part to leaking capillaries; COVID-19 enters the lungs via the ACE2 receptor that then pulls the virus into lung cells where it multiplies. ACE2 controls blood pressure, but it also keeps bradykinin—the substance that makes blood vessels leak—under control. A similar phenomenon occurs with hereditary angioedema, a rare disease. Some side effects of ACE inhibitors, such as dry cough, also resemble symptoms seen with COVID-19. The problems of vascular leakage can be aggravated by an inflammatory phase that can occur after about nine days of infection. Longstanding fluid in the lungs can eventually lead to thrombosis and scarring of the lungs. Interventions that are started early to treat vascular leakage could perhaps prevent these serious complications and keep patients out of the ICU. Radboud researchers are now working on treatments with Icatibant, a product that can inhibit the effects of bradykinin. DOI: 10.7554/eLife.57555
Other News
Genomics Medicine Ireland (GMI), with support from Illumina Cambridge Ltd, will assist research institutions by sequencing genomes free of charge from study participants infected with coronavirus across Ireland. This support will be provided to researchers working to identify protective and risk-bearing genetic factors for COVID-19 and who are sharing their consented anonymized datasets with other authorized researchers through EMBL’s European Bioinformatics Institute (EMBL-EBI) European Genome-phenome Archive (EGA) database. The Clinical Research Facility at St James’s Hospital, which is collaborating with researchers in Trinity College Dublin (TCD), is among the initial research facilities participating in these international efforts. Press release.
The Pathogen and Microbiome Institute (PMI) at Northern Arizona University (NAU) has repurposed its existing biodefense research infrastructure for a COVID-19 Testing Service Center (CTSC) that will grow the SARS-CoV-2 virus and test new drugs against it. The first therapeutic agent to be tested against the COVID-19 virus will be the promising cancer drug 2X-121, developed by the Danish firm Oncology Venture that recently signed a joint research agreement with PMI and NAU. The small molecule is currently being evaluated for the treatment of advanced ovarian cancer in a phase 2 clinical trial at the Dana-Farber Cancer Institute in Boston, which would accelerate its potential use as an antiviral agent. The CTSC will conduct in vivo testing on any existing drugs showing strong virus inhibitory action in vitro. The CTSC is being led by C. Todd French, recently recruited from the University of California Los Angeles for his expertise in pathogen virulence mechanisms. The PMI’s executive director, Paul Keim, is also a world expert in pathogens such as plague and anthrax. Press release.
LabVantage Solutions has announced its new purpose-built COVID-19 LIMS solution. The new solution is designed to jump-start the ability of laboratories everywhere to enter biospecimens into a biobank and rapidly begin conducting COVID-19-related testing and research. The LabVantage COVID-19 Biobanking Accelerator is built on the company’s industry-leading LIMS and Biobanking platforms used by clinical laboratories around the globe. Delivered as a comprehensive Software-As-A-Service (SaaS) solution, the LabVantage COVID-19 Biobanking Accelerator requires no infrastructure investment. Being pre-configured means minimal implementation time is needed with a go-live start possible in less than four weeks. The LIMS Accelerator includes full biobanking capabilities and COVID-19 extraction and testing workflows with related master data for rapid use. It incorporates multiple protocols defined by the CDC for COVID-19 testing, and it can easily accommodate the addition of standard and customer-determined protocols for testing using a variety of approaches, such as RT-PCR, isothermal nucleic acid amplification and serology. Press release.
Digital Science's ReadCube has launched The COVID-19 Research Pass (CRP) programme providing direct access to over 26 million articles and available to anyone studying or writing about COVID-19. Early on in the COVID-19 pandemic, scholarly publishers were quick to open up access to COVID-19 literature to the greater research community. The CRP program expands on these efforts to provide COVID-19 researchers with access to a broader set of content needed in the course of their research. Rather than pre-filtering access to specific articles related to COVID-19, the CRP allows researchers to access any article from participating publishers they may need while studying COVID-19, including both open access and content behind paywalls. Additionally, the program can support COVID-19 researchers who are now working remotely and require remote access to literature. Press release. More information.
A new investigation at Flinders University, funded under the university's COVID-19 Research Grant scheme, is looking at why the presence of bacterial pathogens seems to predispose individuals to severe COVID-19—specifically, respiratory failure. Patients with pre-existing respiratory disease are among those with the highest COVID-19 death rates, and the research will help define the importance of tracking and treating bacterial infection in susceptible populations as a prevention strategy. Press release.
Illumina in investing in SARS-CoV-2 research. Last week, the company released the free Illumina SARS-CoV-2 Data Toolkit, which includes a new DRAGEN RNA Pathogen Detection Pipeline to enable detection of infectious diseases, a DRAGEN Metagenomics Pipeline for outbreak surveillance, an SRA Import App, as well as a GISAID Sharing App. The toolkit integrates with Illumina’s worldwide installed base of 15,000 sequencing systems and is designed to help the global research community and public health officials track the path of the epidemic, understand transmission routes, determine the rate of viral evolution, and understand if the virus is changing in ways that impact therapeutic effectiveness. Press release. The company also donated $1.4 million worth of sequencing systems and related consumables intended to expand SARS-CoV-2 sequencing capabilities and capacity in ten African countries, including the Democratic Republic of the Congo, Egypt, Ethiopia, Ghana, Kenya, Mali, Nigeria, Senegal, South Africa and Uganda. Press release.
ProteoGenix, a global leader in antibody production, is pleased to announce the first Human Immune COVID-19 library for the fast discovery of potent antibodies against SARS-CoV-2. The library, created using blood samples from dozens of recovered COVID-19 patients, is adapted for screening with phage display and strives to meet the rising demands for effective antibodies for a broad range of applications. The library’s vast diversity (1.2 x 1010 different clones) allied to the fast turnaround time and sensitivity of the screening technology, are intended to fast-track the discovery of antibodies with the strongest affinity, specificity, and viral blocking activity. More information.
Researchers in Germany are trying to develop a passive vaccine against COVID-19 by developing monoclonal antibodies that can be used to protect medical personnel, staff in care homes and high-risk patients and potentially also treat patients severely affected by COVID-19 infection. The idea is to inject patients with antibodies that target a specific pathogen in the event of a possible infection. Although the passive vaccine is only expected to offer about two to three months of protection, it’s considered a good option for certain risk groups until an active vaccine is developed. More than 25 antibodies potentially suitable for a vaccine have already been identified. In one investigation, genetically engineered mice vaccinated with components of the coronavirus formed human antibodies that are now being tested for their ability to prevent viral infection in a cell culture system. Next, scientists will test whether the results obtained from cell cultures can also be confirmed in animal experiments. Clinical trials wouldn’t begin for at least six months, with a passive vaccine available in nine months if all goes well. Press release.
PrecisionLife is now offering free use of its unique analytics platform and support from its data and biomedical science teams to the on-going collaborative efforts of the medical research community in the fight against COVID-19 coronavirus. The precisionlife platform can analyse large scale, complex multi-omic and epidemiological data to generate disease insights that are not possible with current tools. It is routinely used to analyse very large anonymised patient datasets (>100,000 patients) and with detailed insights into complex diseases returned within hours. The platform can be used to help identify the complex genetic factors associated with patients’ different disease severity and outcomes, understand risk factors such as smoking, gender, ethnicity, blood group and underlying health conditions, develop tests to identify whether people are at high- / low-risk for serious forms of the disease, inform the hunt for existing drugs that will be effective for given patient sub-groups, especially those at risk of late-stage disease, and identify novel drugs targets especially for more serious late-stage disease. Press release.
At the University of California, Los Angeles (UCLA), researchers have received a pair of grants from the California Institute for Regenerative Medicine, the state's stem cell agency, to pursue treatments and vaccines for COVID-19. One $150,000 award will support a study into how T cells respond to SARS-CoV-2, informing the development of vaccines and therapies that harness the immune cells to fight the virus. Rather than using cells taken from infected people, scientists are taking T cells donated by healthy people and inducing them to mount strong immune responses to parts of the virus in the lab. Their method uses blood-forming stem cells that are converted into dendritic cells using a new method developed by a pair of graduate students. These rare immune cells devour proteins from foreign invaders, including viruses, and then chop them into fragments (antigens) that can trigger an immune response from T cells. Gomperts' $150,000 award will support the use of a human stem cell-derived lung organoid model to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with SARS-CoV-2. Another $150,000 grant will support the use of a three-dimensional lung organoid model to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with SARS-CoV-2. Thousands of drug candidates will be screened, beginning with those approved by the Food and Drug Administration or deemed safe in humans based on a phase one clinical trial. Each award is being matched dollar-for-dollar by the UCLA Broad Stem Cell Research Center. Press release.
Canada just invested $23 million toward development of a COVID-19 vaccine by researchers at the University of Saskatchewan's Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), who have been collaborating with the World Health Organization, the Public Health Agency of Canada and researchers around the world. The award will support pre-clinical testing and two phases of clinical trials. Manufacturing of the prototype vaccine and extensive safety assessment of the vaccine in animal models has been started and will be completed this summer. Clinical testing in humans (all Canadians) is planned for the fall, with the vaccine potentially being available as early as next spring. Canada now has almost 42,000 confirmed cases and 1,974 deaths from COVID-19. VIDO-InterVac is currently completing its vaccine manufacturing facility to Good Manufacturing Practices standards, as required for human vaccine production, with the support of the federal and Saskatchewan governments. Press release.
Researchers at the Center for High Performance Computing at the University of Utah are using the powerful supercomputers of Texas Advanced Computing Center at the University of Texas at Austin to rapidly generate molecular models of compounds relevant for COVID-19. They have been applying Assisted Model Building with Energy Refinement (aka Amber), a molecular simulation suite of software and force fields, to biomolecular simulations with applications in medicine. When the COVID-19 pandemic struck, they turned their attention to discovering drugs that could disrupt the coronavirus. The researchers rapidly generated more than 2,000 molecular models of potential COVID-19 drugs that involved optimizing known crystal structures and then ranking them based on free energetics estimates. They are now continuing their efforts using 2.7 million node hours on Blue Waters, a GPU-based system located at the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign. Press release.
A pulmonary and critical care physician at the Albany Medical Center in New York is collaborating with investigators at the Morgridge Institute for Research and the Department of Biomolecular Chemistry at the University of Wisconsin School of Medicine and Public Health (SMPH) to better understand the molecular profile of COVID-19 and provide insights that may improve treatment. Researchers will be analyzing approximately 150 patient COVID-19 samples—using mass spectrometry to measure lipids, proteins and metabolite—in hopes of uncovering factors that influence whether a patient will suffer from complications such as acute respiratory distress syndrome (ARDS). Previous research has typically focused on proteomics, lipidomics and metabolomics separately. It remains unclear if cytokine storm is a trigger for ARDS. Other potential indicators of disease severity involve blood clotting factors in the vessels of the lung. The researchers will also look for unique gene expression profiles to distinguish between mild and severe cases. Press release.
Entos Pharmaceuticals is collaborating with EpiVax to develop a pan-coronavirus DNA vaccine offering long-term immunity against SARS-CoV-2 infection. Unlike traditional vaccines, it will encode the virus proteins in a DNA plasmid that is then delivered into the patient's own cells by direct fusion. The patient's cells then produce the viral proteins that the body recognizes as foreign, and a potent immune response is mounted. The project will use the Fusogenix platform of Entos that has undergone extensive pre-clinical toxicity and efficacy studies in animal model and has been validated as an intracellular delivery platform for DNA. Press release.
Starting today, Verndari Inc. is evaluating VaxiPatch, a potential vaccine delivery system for COVID-19, at UC Davis. VaxiPatch is a single-dose vaccination kit that uses a dermal patch with a metal microneedle array to deliver vaccines. The technology eliminates the need for refrigeration, facilitates high-volume, automated manufacturing of vaccines and can potentially be self-administered on the subject's arm. Researchers amended an existing protocol for influenza to test the COVID-19 vaccine in rats and will compare administration of the VaxiPatch to an injectable vaccine and monitor the rodents for adverse reactions as well as collect blood samples to evaluate immune responses. Verndari is also in discussions with the California National Primate Research Center at UC Davis to conduct further testing in rhesus macaques. In preparation for human trials, the company is working on an agreement with UC Davis to manufacture the clinical version of the vaccine kit. Press release.
Nuritas has received a grant from Partnership for Advanced Computing in Europe (PRACE) to identify therapeutic peptides for the treatment of patients with COVID-19. Under the terms of the grant, Nuritas will employ its proprietary AI platform to identify peptides with antiviral properties as well as peptides with cytokine regulatory properties, with the goal of creating a therapeutic ‘peptide cocktail’. If successful, this approach has the potential to slow or stop disease progression by both mitigating viral replication and modifying the cytokine-based inflammatory response known to drive respiratory damage in patients with COVID-19. Press release.
