COVID-19 Update: Structural Modeling, New Funding, Vaccine News
June 5, 2020 More updates on SARS-CoV-2 research and COVID-19 from the Bio-IT Community including an app to create COVID-19 severity scores, new insights into viral behavior, modeling tools for the virus structure, and an influx of funding from Illumina, the Department of Defense, AstraZeneca, and more.
Literature Updates
A new mobile app created by researchers at NYU College of Dentistry, uses artificial intelligence (AI) to assess risk factors and key biomarkers from blood tests, producing a COVID-19 "severity score." Using data from 160 hospitalized COVID-19 patients in Wuhan, China, the researchers identified four biomarkers measured in blood tests that were significantly elevated in patients who died versus those who recovered: C-reactive protein (CRP), myoglobin (MYO), procalcitonin (PCT), and cardiac troponin I (cTnI). These biomarkers can signal complications that are relevant to COVID-19, including acute inflammation, lower respiratory tract infection, and poor cardiovascular health. The researchers then built a model using the biomarkers as well as age and sex, two established risk factors. They trained the model using a machine learning algorithm, a type of AI, to define the patterns of COVID-19 disease and predict its severity. When a patient's biomarkers and risk factors are entered into the model, it produces a numerical COVID-19 severity score ranging from 0 (mild or moderate) to 100 (critical). The model was initially validated using data from 12 hospitalized COVID-19 patients from Shenzhen, China. These findings are published in Lab on a Chip, a journal of the Royal Society of Chemistry. Since then, the researchers further validated the model using data from more than 1,000 New York City COVID-19 patients. After optimizing the clinical utility of the app at the Family Health Centers at NYU Langone in May, the researchers aim to roll it out nationwide in the coming weeks. DOI: 10.1039/D0LC00373E
Scientists at the UNC School of Medicine and the UNC Gillings School of Global Public Health have characterized the specific ways in which SARS-CoV-2 infects the nasal cavity. The findings suggest the virus tends to become firmly established first in the nasal cavity, but in some cases the virus is aspirated into the lungs, where it may cause more serious disease, including potentially fatal pneumonia. Their findings were published in Cell. DOI: 10.1016/j.cell.2020.05.042
Researchers at the University of Tokyo have introduced a new technique called Fate-seq to determine the fate of a genetic sequence, whether it will persist or degrade based on its stability. Using Fate-seq, the team identified a SARS-CoV-2 genetic fragment that may enhance survival of the virus and appears—in predictive models—to be very stable. These sequences have the potential to enhance the stability of viral RNA genomes, thereby augmenting viral replication efficiency and virulence. The work was published in Biochemical and Biophysical Research Communications. DOI: 10.1016/j.bbrc.2020.05.008.
A team of structural biologists at the University of Virginia have created a Web resource that provides scientists a quick assessment of SARS-CoV-2 structural models and enhanced versions of these structures, when possible. Their goal is to carefully validate the models deposited into the Protein Data Bank of CoV-2 proteins, with the aim of helping the biomedical community to establish a validated database. The team has described the new resource in a free access article published in the FEBS Journal. DOI: 10.1111/febs.15366
Researchers at Colorado State University attempted to use riboflavin and ultraviolet light to reduce the SARS-CoV-2 virus in infected human plasma and whole-blood products. The study was published May 29 in PLOS ONE. The research team used the Mirasol Pathogen Reduction Technology System, a technology owned by Terumo BCT and invented by Ray Goodrich, senior author of the study, to treat nine plasma and three whole-blood products for the study. Riboflavin and UV light reduced the infectious titer of SARS-CoV-2 below the limit of detection for plasma products at 60–100% of the recommended energy dose. DOI: 10.1371/journal.pone.0233947
Scientists from the University of California, Riverside, report in the journal Molecules that two proteases on the surface of host cells and responsible for processing viral entry could be inhibited, preventing SARS-CoV2 from invading the host cell. The team recognized that in addition to a previously identified protease called TMPRSS2, the new SARS-CoV-2 coronavirus could also be processed by an additional human protease, called furin, for viral entry. They suggest that furin may be essential for the viral entry and/or egress in highly pathogenic strains DOI: 10.3390/molecules25102424
Researchers from Peking University (PKU) have successfully identified multiple highly potent neutralizing antibodies against the novel coronavirus SARS-CoV-2 by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. The findings were published in Cell. DOI: 10.1016/j.cell.2020.05.025
Company Updates
Ginkgo Bioworks has announced a $70M investment from Illumina and existing Ginkgo investors, General Atlantic and Viking Global Investors to fund infrastructure that could enable rapid epidemic response. Ginkgo aims to achieve unprecedented scale with its automation capabilities, leveraging Illumina's next-generation sequencing (NGS) technology to enable widespread testing for COVID-19. Ginkgo's hardware and software that is designed for the large-scale automation of biological experiments. In combination with NGS, the companies believe it has the potential to significantly increase COVID-19 testing capacity, contributing to the testing volume that many public health experts believe is necessary for slowing the spread of the virus. Press release.
Southwest Research Institute is virtually screening millions of drug compounds using Department of Defense supercomputers to search for and test possible treatment options for the novel coronavirus 2019. The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. (HJF) has awarded SwRI a $1.9 million, one-year contract to support these efforts to identify potential COVID-19 treatments. SwRI is working with the DOD High Performance Computing Modernization Program to rapidly screen potential drug compounds using SwRI's 3D drug screening software tool, Rhodium. Using supercomputers speeds up the screening process allowing evaluation of possible therapeutic compounds to increase from 250,000 compounds a day to more than 40 million compounds in just one week. Press release.
AstraZeneca has donated $500,000 to the American Thoracic Society’s COVID-19 Crisis Fund. The Crisis Fund will help clinicians and scientists develop and disseminate research, education and scientific recommendations to providers in the pulmonary and critical care communities, as well as to support other clinicians in need of expanding their skill set during this emergency. It is the ATS's hope that donations to the fund will motivate other industry groups to share their resources in helping to address the significant needs arising from the COVID-19 crisis. Press release.
Otago and ESR have received $25 million in total government grants to lead an international team of scientists to sequence the genomes of all of New Zealand's positive COVID-19 cases and track how the virus spread across New Zealand. The fund allows for the rapid development of innovative solutions by New Zealand-based entities in response to COVID-19, and aims to alleviate the direct impacts of the virus threat. Their team of 14 world-leading experts in virus evolution and phylodynamics will create a user-friendly web browser application that will be available to the public online and will track and explain the evolution, epidemiology, population dynamics and transmission chains of COVID-19 in New Zealand. Press release.
SAS has launched COVID-19 Scientific Literature Search and Text Analysis, a free visual text analysis environment that uses artificial intelligence (AI) and machine learning to quickly search tens of thousands of research articles on COVID-19. Leading research groups have gathered and released to the public more than 50,000 full-text scientific research articles on COVID-19 and other coronaviruses through the COVID-19 Open Research Dataset (CORD-19). SAS Viya powers the interactive environment through advanced analytics and AI methods that help researchers explore the CORD-19 dataset. Using SAS Visual Text Analytics and SAS Visual Data Mining and Machine Learning, SAS augments the dataset with models developed by linguists and health and life sciences experts. Researchers can explore topics such as PPE effectiveness, social distancing efficacy and the transmission environment. The models also extract and visualize quantitative data, such as the incubation period and reproduction number of COVID-19. The free and publicly available environment aims to quickly and efficiently connect the global research community with the most relevant scientific literature through its self-guided, cloud-based system. Press release.
Chimeron Bio, an RNA therapeutics company, and George Mason University's National Center for Biodefense and Infectious Diseases (NCBID), are partnering to develop a Coronavirus (COVID-19) vaccine. The vaccine development will be based on Chimeron Bio's ChaESARTM self-amplifying RNA technology and will integrate Mason's complimenting expertise and Biomedical Research Laboratory (BRL), a National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) supported, state-of-the-art Regional Biocontainment Laboratory for the rapid screening of the company's vaccine pipeline. Press release.
Intravacc and EpiVax have entered into a collaboration agreement to further progress a novel vaccine against COVID-19, based on Intravacc's proprietary Outer Membrane Vesicles (OMV) technology platform. For this joint research project, Intravacc will combine its safe and immunogenic OMV delivery platform with synthetically produced COVID-19 epitopes (protein allergens), designed and optimized by EpiVax using advanced immunoinformatics tools, in order to generate a safe and highly effective T-cell response against SARS-CoV-2 and related coronaviruses. Pre-clinical studies will start immediately so as to select the best candidate peptides for the vaccine. Intravacc will utilize its in-house pilot-scale facility for the GMP production of the OMV-peptide vaccine, for clinical (phase I) studies expecting to start in Q4 2020. Press release.
SAB Biotherapeutics (SAB) has developed a novel therapeutic candidate for COVID-19. SAB produces fully human polyclonal antibodies without the need for human plasma donors by leveraging genetically engineered cattle to produce fully human antibodies. SAB’s candidate deploys the same natural immune response to fight the disease as recovered patients, but with a much higher concentration of targeted antibodies the company says. SAB-185 is being developed in collaboration with CSL Behring and initial funding up to $9.4 million supported by the Biomedical Advanced Research Development Authority (BARDA). Press release.
Baylor College of Medicine and Texas Children’s Hospital Center for Vaccine Development has extended their ongoing collaboration with Infectious Disease Research Institute (IDRI) to advance its COVID-19 vaccine candidate, pursue a key manufacturing step and fill sufficient vials to accelerate the transition into Phase 1 clinical trials. Through this alliance, Baylor and Texas Children’s, in conjunction with PATH, a global nonprofit organization dedicated to improving public health, will work with IDRI to formulate and vial enough of its COVID-19 vaccine to accelerate its testing into Phase 1 clinical trials. The aim is to have the Covid-19 vaccine evaluated in humans later this fall. Together, these institutions will prepare the stage for the advancement of a low-cost, safe and effective vaccine to prevent COVID-19 locally and globally. Press release.
The Center for International Health, Education and Biosecurity (Ciheb) at the University of Maryland School of Medicine's Institute of Human Virology was awarded $4 million from the U.S. Centers for Disease Control and Prevention (CDC) to support COVID-19 response activities in Botswana, Nigeria, Malawi, and Mozambique. In Nigeria, the award of $2.1 million will support a population-based epidemiological study to estimate COVID-19 prevalence in communities, household transmission, the proportion of subclinical infections, and risk factors for infection. In Botswana, the award of $810,000 will support the development of an influenza-like illness (ILI) and severe acute respiratory infection (SARI) surveillance systems for the Botswana Ministry of Health and Wellness to capture community circulation and transmission of SARS-CoV-2. In Malawi, the award of $795,000 will enhance the Malawi Ministry of Health's laboratory capacity in five primary areas: training, quality control, supplies, services, and waste management. Finally, in Mozambique, the award of $380,000 will ensure maintenance for ABI 7500 and ABI 7900 PCR instruments installed at the National Institute of Health in Maputo Province. The award will also provide GeneXpert operations training, support the installation of the COVID-19 software and instrument hardware, and ensure DISA-Lab operational connectivity on GeneXpert instruments at 11 locations across the nation. Press release.
A Texas A&M team received a National Science Foundation grant to pursue the lab-on-a-chip technology to rapidly identify antibodies for therapeutics to fight COVID-19. So far, the team has successfully built a prototype device of PRESCIENT (Platform for the Rapid Evaluation of antibody SucCess using Integrated microfluidics ENabled Technology) and tested its feasibility using the hepatitis virus, a type of coronavirus, and demonstrated that antibodies produced by a single cell could neutralize infection of the virus within the pico-liter-volume bioreaction chamber. This work has now been accepted by the journal Lab on a Chip according to the researchers and will be published in an upcoming issue. Press release.