Mines at Catalyst Response to COVID-19
Project 1: Manufacturing of personal protective equipment (PPE)
Hospitals are faced with a shortage of PPE putting hospital workers and patients at a dramatic risk of infection. Mines, including the Advanced Manufacturing Center, ADAPT, in collaboration with the National Renewable Energy Laboratory (NREL) have developed a streamlined pipeline for the creation of face shields at Mines/NREL facilities for distribution among hospitals in Colorado who need them, combining the unique expertise in the supply chain, 3D printing and scale-up capabilities of the two institutions.
Project 2: AI of clinical and claims data
The Colorado Hospital Association (CHA) administers hospital claims data that provides a unique source of information on how hospitals across Colorado, both in the Denver metro as well as rural areas, cope with COVID-19. Large numbers of digital health companies develop digital health tools, such as telehealth, care coordination, and diagnostic testing, that play a direct role in combating COVID-19. Mines’ expertise in artificial intelligence (AI) will be deployed to analyze CHA data and provide student workforce and training to collaborate with local industries developing predictive models, for example, to predict the impact of co-morbidities on COVID-19.
Project 3: AI for drug and target discovery and diagnostics development.
Machine learning (ML) and simulations are integral tools for AI. Large amounts of clinical, epidemiological, sequence and molecular data has been collected as evidenced by more than 1000 scientific articles relating to the novel coronavirus and a number of dedicated databases and websites disseminating these large data. We will leverage ML and simulations for drug and biomarker discovery for treatment and diagnostics in a collaboration with the nation’s top specialists in computational biology of host-pathogen interaction networks.
Seeking: experimental validation, prioritization for clinical practice
Project 4: AI for hospital clinical operations.
As hospitals assess their clinical operations and readiness both now and for the duration of the pandemic, operations research tools are needed to help them ensure that their facilities have the necessary expertise, equipment, and personnel in place to provide optimal care while also protecting their staff. Prior to the coronavirus pandemic, there was already a strain on scarce nursing resources, and while we’ve seen nurses and other medical personnel selflessly and courageously jumping into the fray to help areas of greatest need, we are reminded that this will be a marathon and not a sprint. Until adequate PPE supplies exist, we can reasonably expect our providers to become ill and exit the workforce at an accelerated rate. As of last week, 2,629 Italian health care workers (8.3% of overall cases) had experienced a COVID-19 infection, with infections attributed to inadequate equipment and asymptomatic exposures. Thus, hospitals are assessing how to manage their resources for the whole curve, not just for the immediate influx, but for the duration.We are working with emergency departments (ED) in Chicago and NYC to help them appropriately allocate resources across short and longer term horizons. The proposed technology develops a new predictive analytics engine grounded in optimization modeling for emergency department use under short-term and medium term covid conditions. A simulation component will be introduced to allow ED leaders to consider and compare operational strategies generated via a predictive analytics engine grounded in optimization modeling.
Seeking: operations research expertise, python, statistics,
Project 5: Sterilization of N95 face masks FOR SAFE REUSE
In an effort crossing state boundaries we are collaborating to develop novel sterilization protocols for N95 face masks using dense phases of carbon dioxide (liquid, supercritical) made by companies such as TharProcess and Coolclean. Testing for retained particle filtration functionality and testing of complete inactivation of the virus have begun in the Pittsburgh, Minneapolis and South Carolina areas. The exemplary re-purposing of CO2 emitted from breweries for the CBD industry in Colorado could be a rapid prototype for re-purposing CO2 for PPE sterilization in Colorado hospitals.
Seeking collaborators with BSL3 capabilities to test for coronavirus infectivity after sterilization treatment.
Project 6: Structure-based drug design Coronavirus protease SARS-CoV-2 3CLpro and MMP inhibitor Periostat
One of the drug targets among coronaviruses is a protease called Mpro or 3CLpro. The current pandemic-causing virus SARS-CoV-2 also produce 3CLpro in infected human cells. The protease activity of 3CLpro is essential to produce functional proteins necessary for coronavirus propagation. Therefore, an inhibition of protease activity would potentially be beneficial for coronavirus patients. A search for similar human proteases led to human matrix metalloproteases (MMPs), in particular MMP1. Both 3CLpro and MMP1 have two parts connected by a linker and computational molecular docking suggests 3CLpro binds collagen similar to MMP1. This is important because MMP1 can degrade highly protease-resistant type-1 collagen, the primary component of structural scaffold for cells in the human body. In the context of COVID-19, the disease caused by SARS-CoV-2, a pattern is emerging about the disease pathology: 1) increased structural damage of lungs (more degradation of collagen), 2) increased fibrosis post recovery (more deposition of collagen), and 3) increased blood clots. These pathologies are related to collagen (structural damage of lung and fibrosis), fibrin (blood clot), and MMPs (proteases that are capable of degrading collagen and fibrin) among myriad of other possibilities. Due to similarities between 3CLpro and MMP1 as suggested by computational studies, we posit that MMP inhibitor might be a potential candidate for treatment. Fortunately, there is Periostat, an FDA-approved MMP inhibitor that is a synthetic derivative of tetracycline. Recently, we observed that tetracycline holds the two parts of MMP1 and inhibits MMP1 inter-domain dynamics necessary for MMP1 activity. Interestingly, tetracycline binds the two parts of 3CLpro in a similar way. We are currently working on understanding how 3CLpro interacts with type-1 collagen, MMP1, and tetracycline. If successful, our research might lead to another avenue for COVID-19 treatment.
- Heit, J.A., A.T. Cohen, and F.A. Anderson, Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. 2005, Am Soc Hematology.
- Mahan, C.E., et al., Venous thromboembolism: annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates. Thrombosis and haemostasis, 2012. 107(02): p. 291-302.
- Deitelzweig, S., et al., Prevalence of clinical venous thromboembolism in the USA: current trends and future projections. American journal of hematology, 2011. 86(2): p. 217-220.
- Collen, D., The plasminogen (fibrinolytic) system. Thrombosis and haemostasis, 1999. 82(02): p. 259-270.
- Wendelboe, A.M., et al., Global public awareness of venous thromboembolism. Journal of Thrombosis and Haemostasis, 2015. 13(8): p. 1365-1371.
- dela Peña, I., et al., Strategies to extend thrombolytic time window for ischemic stroke treatment: an unmet clinical need. Journal of stroke, 2017. 19(1): p. 50.
- Sidelmann, J.J., et al. Fibrin clot formation and lysis: basic mechanisms. in Seminars in thrombosis and hemostasis. 2000. Copyright© 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New ….
- Mannello, F., Serum or plasma samples? The “Cinderella” role of blood collection procedures preanalytical methodological issues influence the release and activity of circulating matrix metalloproteinases and their tissue inhibitors, hampering diagnostic trueness and leading to misinterpretation. 2008, Am Heart Assoc.
- Van Doren, S.R., Matrix metalloproteinase interactions with collagen and elastin. Matrix Biology, 2015. 44: p. 224-231.
- Morrison, C.J., et al., Matrix metalloproteinase proteomics: substrates, targets, and therapy. Current opinion in cell biology, 2009. 21(5): p. 645-653.
- Birkedal-Hansen, H., et al., Matrix metalloproteinases: a review. Critical Reviews in Oral Biology & Medicine, 1993. 4(2): p. 197-250.
- Parks, W.C., et al., The Role of Matrix Metalloproteinases in Cellular Invasion and Metastasis, in Extracellular Matrix Degradation. 2011, Springer Berlin Heidelberg. p. 145-191.
- Song, F.Y., et al., Matrix metalloproteinase dependent and independent collagen degradation. Frontiers in Bioscience, 2006. 11: p. 3100-3120.
- Cunningham, K.S. and A.I. Gotlieb, The role of shear stress in the pathogenesis of atherosclerosis. Laboratory Investigation, 2005. 85(1): p. 9-23.
- Chakraborti, S., et al., Regulation of matrix metalloproteinases: An overview. Molecular and Cellular Biochemistry, 2003. 253(1-2): p. 269-285.
- Lauer-Fields, J.L., D. Juska, and G.B. Fields, Matrix metalloproteinases and collagen catabolism. Biopolymers, 2002. 66(1): p. 19-32.
- Bissell, M.J. and D. Radisky, Putting tumours in context. Nature Reviews Cancer, 2001. 1(1): p. 46-54.
- Cleutjens, J.P.M., et al., Regulation of Collagen Degradation in the Rat Myocardium after Infarction. Journal of Molecular and Cellular Cardiology, 1995. 27(6): p. 1281-1292.
- Kivirikko, K.I., Collagens and Their Abnormalities in a Wide Spectrum of Diseases. Annals of Medicine, 1993. 25(2): p. 113-126.
- Liotta, L.A., et al., Metastatic Potential Correlates with Enzymatic Degradation of Basement-Membrane Collagen. Nature, 1980. 284(5751): p. 67-68.
- Ross, R. and E.P. Benditt, Wound Healing and Collagen Formation .1. Sequential Changes in Components of Guinea Pig Skin Wounds Observed in Electron Microscope. Journal of Biophysical and Biochemical Cytology, 1961. 11(3): p. 677-&.
- Control, C.f.D. and Prevention, Leading causes of death and numbers of deaths, by sex, race, and Hispanic origin: United States, 1980 and 2014 (Table 19). Health, United States, 2015.
Every individual is affected and many want to help, but it is not clear how. This website and initiative, led by Mines at Catalyst and the University’s Biosciences and Engineering faculty, is out attempt to bring different industries and disciplines together, to repurpose technology, invent new technology and develop creative solutions to unprecedented problems. The expertise and capabilities needed to combat the virus require an unprecedented convergence of disciplines. We plan to facilitate communication and cooperation for AI in bio and health at the Colorado School of Mines with others interested in collaboration with us to combat the deadly virus with all of the modern arsenal of technology available to us.
Mines is well known for its expertise in technology and engineering, and with over 45 faculty working in bio and health related application areas, we have the capacity to understand the biological intricacies of a viral pandemic. The headquarter for this initiative is the Mines suite within the Catalyst Health Tech Integrator (HTI) in RiNo, where Mines is embedded in a network of industries and stakeholders in the health sector, ensuring the relevance of the collaborative infrastructure for public health in Colorado.
In response to our list of projects here, if you can take action, provide additional help, or have inquiries, or if you have a project that involves Mines and COVID-19 that you would like to see listed here, please fill out the form below or contact Judith Klein at email@example.com
If you can take action, provide additional help, or just have inquiries please let us know in the form below. Please stay safe.
– Thank you.