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MIT, Oak Ridge National Laboratory Join In Consorted Efforts To Address COVID-19



April 24, 2020 | As SARS-CoV-2 (COVID-19) continues impacting individuals and communities on a global scale, the bio-IT community is working around the clock to provide both relief and solutions. Their latest efforts include a COVID-19 Research Database, specialized proteins to combat immune overreaction to the virus, promising animal models, and much more.

Literature Updates

Researchers at the Massachusetts Institute of Technology have developed specialized proteins, similar in structure to antibodies, that they believe could halt the burst of immune overreaction—cytokine storms—seen in COVID-19 patients. The idea is to inject the water-soluble receptor proteins into the body where they sop up excess cytokines like a sponge, alleviating symptoms from the infection. Initial findings published in Quarterly Review of Biophysics (QRB) Discovery, and the next step is to test the proteins in human cells and in animal models of cytokine release and coronavirus infection. Researchers hope to license the technology quickly and collaborate with pharmaceutical and biotech companies that can help to move it toward clinical trials. DOI: 10.1017/qrd.2020.4

Researchers from Oregon Health & Science University and the Portland VA Research Foundation have discovered that genetic variability in the human immune system may affect susceptibility to and severity of infection by SARS-CoV-2. They show that individual HLA (a component of the immune system containing multiple genes,) haplotype (a set of DNA variations that tend to be inherited together) and full genotype variability likely influence the capacity to respond to SARS-CoV-2 infection, and they note that certain alleles could be associated with more severe infection. Pairing HLA typing with COVID-19 testing could improve assessment of viral severity in the population and, once a vaccine is developed, individuals with high-risk HLA types could be prioritized for vaccination. The research published in the Journal of Virology. DOI: 10.1128/JVI.00510-20

Animals are a promising model for testing COVID-19 therapeutics, suggests a study published in Science. Researchers report that SARS-CoV-2 gave cynomolgus macaques a mild COVID-19-like disease even as they were shedding the virus, as happens in asymptomatic humans. Viral RNA was detected at higher levels and for longer duration in older macaques, although none showed the severe symptoms that older humans do. As with influenza, the animals shed the virus from the respiratory tract very early during infection as compared to other coronaviruses; this could explain the explosive global spread of COVID-19 and why case detection and isolation may not be as effective as public health officials hope. DOI: 10.1126/science.abb7314

Researchers from CSIRO, Australia's national science agency, have unveiled a new approach to analyzing the genetic codes of the SARS-CoV-2 virus in Transboundary and Emerging Diseases. The novel visualization platform is underpinned by bioinformatics algorithms originally used to analyze the human genome. Highly complex analysis of the genome sequence of the virus has already helped to determine which strains are suitable for testing vaccines underway at the Australian Centre for Disease Preparedness in Geelong, the only high biocontainment facility of its kind in the Southern Hemisphere. SARS-CoV-2 will likely evolve into several distinct clusters that share mutations, which will likely not affect the development and evaluation of COVID-19 vaccines, therapies, and diagnostics. But it is nonetheless important information to monitor, so study authors are calling on the international research community to share de-identified details of case severity and outcome, and other relevant metadata such as comorbidities and smoking status, alongside the genomic sequences of the virus. DOI: 10.1111/tbed.13588

A new study by researchers at Boston Children’s Hospital and Massachusetts Institute of Technology pinpoints the three likely cell types infected by SARS-CoV-2—goblet cells in the nose that secrete mucus, type II pneumocytes that help maintain the alveoli and enterocytes that line the small intestine and involved in nutrient absorption. They are the only ones expressing both receptor ACE2 and enzyme TMPRSS2, which previous research has shown are used by SARS-CoV-2 to gain entry into human cells. Intriguingly, the ACE2 gene is stimulated by interferon, one of the body's main defenses when it detects a virus. Interferon (which is being tested as a treatment for COVID-19) turns the ACE2 gene on at higher levels, potentially giving the virus new portals to get in. Researchers speculate that the virus might be exploiting that normal protective response. Findings published in Cell and may raise new lines of inquiry around ACE inhibitors, which work in the same pathway as ACE2 and may affect people’s risks. DOI: 10.1016/j.cell.2020.04.035 [Pre-proof PDF]

A team of Chinese scientists recently developed two novel compounds that inhibit the SARS-CoV-2 main protease (Mpro) and the one with lower toxicity is a good drug candidate for further clinical studies, based on results of a study published in Science. Preclinical research on the compound is now proceeding. Research data is being shared with scientists around the world to accelerate the development of anti-SARS-CoV-2 drugs. DOI: 10.1126/science.abb4489

Other News

A consortium of leading healthcare companies today announced the launch of the COVID-19 Research Database, a secure repository of HIPAA-compliant, de-identified and limited patient-level data sets made available to public health and policy researchers to extract insights to help combat the COVID-19 pandemic. The database is a pro bono, cross-industry collaboration. Collaborators include Advarra, Aetion, AnalyticsIQ, Arcadia.io, Berkeley Research Group, BHE, Change Healthcare, Datavant, Elsevier, Glooko, Health Care Cost Institute, Healthjump, Helix, Medidata (a Dassault Systèmes company), Mirador Analytics, Munich Re Life US, Office Ally, OMNY, Parexel, Prognos Health, QIAGEN, SAS, Snowflake, Sumitomo Dainippon Pharma, Symphony Health, Veradigm, and Verana Health. It comprises a large, diverse repository of real-world data, including medical claims, pharmacy claims, electronic health records, and demographic data. In addition to the underlying data, the repository integrates privacy-preserving patient linking technology and statistical certification, connecting data sources in a HIPAA-compliant manner to provide a more complete view of the patient journey. Researchers can access the COVID-19 Research Database via an analytic platform, enabling them to conduct large-scale studies while protecting patient privacy. Press release.

Using data from Elsevier’s PharmaPendium product, which includes searchable FDA/EMA drug approval documents, as well as pharmacokinetic and efficacy data, ExactCure, a personalized medicine startup that uses AI technology to reduce medication errors, is developing personalized model simulations that will provide information to physicians to improve the dosing of COVID-19 related therapies. PharmaPendium will provide ExactCure with pharmacokinetic information for approximately 20 approved drugs that have been widely cited in the literature and the news, such as Hydroxychloroquine, Chloroquine, Lopinavir/Ritonavir and Azithromycin, including their regulatory-approval datasets. ExactCure will use this data to build drug-specific exposure models that allow the prediction of pharmacokinetic properties (e.g. Cmax, AUC, Tmax etc). Press release.

Lore IO, providers of an AI-powered common data model that enables unified data views and faster vendor onboarding, has announced its free COVID-19 Data Onboarding Initiative, a program designed to help pharmaceutical organizations shorten development cycles to speed drug readiness. The program allows organizations to onboard data from up to three unique sources in only 30 days instead of months which is the time it typically takes using traditional methods. Lore IO's COVID-19 Data Onboarding Initiative focuses on expediting the onboarding and transformation of three vendor sources of industry data, which allows the user to create a unified view of the data for analysis and accelerate the execution of their go-to-market plan. More information.

Scripps Research has established an international network of collaborating scientific laboratories to leverage ReFRAME, the world's leading drug repurposing collection, to find antiviral compounds against the novel coronavirus. Calibr, the drug development division of Scripps Research, established the collection in 2018 to tackle areas of urgent unmet medical need. The collection comprises over 14,000 compounds. Since the therapeutic properties of the drugs are already well-characterized, they can be rapidly screened and advanced into a patient setting. ReFRAME is part of the COVID-19 Therapeutics Accelerator launched by funders that include the Bill & Melinda Gates Foundation. Many of Calibr's collaborators are experts in virology and antiviral therapeutics, including Mount Sinai in New York and the Rega Institute for Medical Research in Belgium that is working with Scripps Research on finding drugs that prevent SARS-CoV-2 viral replication. Calibr and the Gates Foundation are working to establish collaborations with leading pharmaceutical companies to further augment ReFRAME's collection of antiviral compounds for future pandemic responses. Press release.

Researchers at Protein Production UK, a collaborative project led by The Rosalind Franklin Institute, have isolated nanobodies (antibodies found in llamas, alpacas, and camels) that bind to the “spike” protein of the SARS-CoV-2 virus and are making them widely available to other research groups around the world. Their high stability, small structure and specificity makes them ideal for the purification and stabilization of proteins and protein structures prior to imaging with techniques such as cryo-electron microscopy. Also under investigation is whether the nanobodies, or therapies derived from them, could be used to create highly specific “blockers” that could contribute to treatments for COVID-19 by preventing the SARS-CoV-2 virus from binding to human cells and causing infection. The nanobodies additionally have diagnostic potential. The next step for researchers at The Franklin is to identify which nanobodies have “binding” and which have “binding and neutralizing” actions, requiring them to search for a wider range of nanobodies and compare their action to human antibodies derived from patient samples. Press release.

A scientist at Tel Aviv University was awarded U.S. patent for his novel coronavirus vaccine design. The patent covers a vaccine that targets the virus’s Achilles’ heel, its receptor-binding motif (RBM), a tiny feature of its "spike" protein that is only 50 amino acids long. Researchers at the university expect to have a reconstituted RBM of SARS- CoV-2 soon, which will be the basis for a new vaccine that could be ready for use within 12 to 18 months. Press release.

Nanoengineers at the University of California San Diego are working on a COVID-19 vaccine using a plant virus that infects legumes and has been engineered to look like SARS-CoV-2. The team's goal is to use plants to create a stable, easy-to-manufacture vaccine that can be shipped around the globe. It will be packaged in slow-release microneedle patches that patients can wear on their arm to painlessly self-administer the vaccine in a single dose. Researchers are customizing methods used to mass-produce plastic products like Legos and disposable cutlery to fabricate the microneedle patches. Press release.

A large collaborative effort, led by researchers at U. S. Department of Energy's Argonne National Laboratory, is combining artificial intelligence with physics-based drug docking and molecular dynamics simulations to rapidly home in on the most promising molecules against COVID-19 to test in the lab. The project is using several of the most powerful supercomputers on the planet—including those at the Texas Advanced Computing Center (TACC), Summit at Oak Ridge National Laboratory, Theta at the Argonne Leadership Computing Facility, and the San Diego Supercomputing Center—to run millions of simulations, train the machine learning system to identify the factors that might make a given molecule a good candidate, and then further explore the most promising results. The team is currently exploring the COVID-19 main protease and will soon begin work on larger proteins that are more challenging to compute but may prove important (e.g., simulation of an all-atom model of the entire virus, which is being produced on the Frontera supercomputer at TACC). The work uses DeepDriveMD (Deep-Learning-Driven Adaptive Molecular Simulations for Protein Folding), a toolkit jointly developed by researchers at Argonne and Rutgers University/Brookhaven National Laboratory. Press release.

A group of U.S. universities, national labs and corporations have formed a consortium offering computing power to help researchers more rapidly build computer models of the SARS-CoV-2's parts, which could aid in developing new therapeutics, according to an article in Chemical & Engineering News. Among the free computing resources are Google's and Amazon's extensive cloud services and some of the world's most powerful supercomputers. Similar efforts are underway in Europe, China and elsewhere. Current projects include a study on protein inhibitors of viral enzymes that could prevent SARS-CoV-2 from replicating, using powerful supercomputers from Oak Ridge National Laboratory.

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