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 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 faceshields at Mines/NREL facilities for distribution among hospitals in Colorado who need them, combining the unique expertise in 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.

References

 

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     Our society is facing a public health crisis due to the COVID-19 pandemic caused by a biological pathogen, the novel coronavirus, that first appeared in Wuhan, China in December 2019.  As of March 31, 2020, COVID-19 has claimed 42,354 deaths world-wide and close to a million people confirmed to be infected. The largest number of confirmed cases of any country is in the US: 200,000 people diagnosed with an unknown number of undiagnosed cases. In Colorado, we have 2,966 confirmed cases, 509 patients are hospitalized and 69 have died. Life as we know it is on hold, affecting everyone in Colorado and the world.

     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 judithklein@mines.edu

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.

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