Chemistry researchers fighting COVID-19 on several fronts

Date

05/13/20

Projects range from better COVID-19 testing to stopping the virus altogether

Researchers in the Department of Chemistry are applying their expertise to this healthcare crisis in a variety of ways, including designing and producing protective equipment for front-line healthcare workers, creating components for virus test kits, developing more accurate widely-deployable testing methods to better detect COVID-19 and stopping the virus, and future coronavirus pathogens, altogether.

Early on in the pandemic, efforts focused on immediate needs of frontline healthcare workers as Professor Martin Burke was involved with a team of engineers, physicians, researchers and designers from the university and from Carle Health who developed and launched production of a face shield for health professionals responding to COVID-19 cases. Burke harnessed the collective power of the Health Maker Lab, an interconnected network of making facilities across campus that can generate almost anything, to lead a highly interdisciplinary effort between the university and the community to meet other urgent needs of front-line healthcare workers. Their efforts have produced N-95 respirators, Powered Air Purifying Respirator shields, intubations shields, disposable and reusable gowns, and masks, all of which were manufactured and delivered to health care workers, along with mid- and small-scale sterilization technologies to sanitize manufactured personal protective equipment and enable that equipment to be reused.

Collaboration has been part of other projects involving chemistry faculty members, including Yi Lu, who is working with a University of Illinois at Chicago colleague, to develop more accurate diagnostic virus testing methods. Burke, along with professors Jeffrey Moore and Doug Mitchell, helped provide COVID-19 testing supplies that are in drastically short supply; and Burke and Professor Paul Hergenrother are involved in the SHIELD initiative to strategically deploy rapid and scalable COVID-19 virus and virus-antibody testing, frontier modeling and contact tracing platforms as part of a broad effort to reopen the University of Illinois community as safely as possible.

Other chemistry faculty have begun focusing efforts on completely stopping the virus, and even future coronavirus-related diseases, including Professor Wilfred van der Donk, who is researching compounds that could stop the virus from entering human cells altogether, and Professor Angad Mehta, who is working on universal platforms for vaccines to address COVID-19 and future coronavirus derived pathogens.

Read more about each of these important projects in the Department of Chemistry:
 

Head shot of Professor Angad Mehta

Angad Mehta: The search for universal coronavirus vaccines

In addition to the current COVID-19 strategies of increasing testing capabilities and practicing social distancing, it has become imperative to develop therapeutic strategies as well, like drugs that can help treat patients and vaccines that can ultimately prevent the disease caused by the virus. 

The universal vaccine platforms that Professor Angad Mehta envisions could be fundamentally important and groundbreaking and positively impact both short-term and long-term vaccine strategies that are imperative in tackling this global challenge. To carry out this research, he has received a grant from the National Science Foundation, specifically a RAPID grant for COVID-19-related projects. 

Several therapeutic options, including various vaccine candidates are in clinical trials now, but as Mehta explains, the constant and sudden emergence of new coronavirus derived pathogens, including the SARS-CoV-2, accentuates the need to develop coronavirus vaccine platforms that can be broadly applied to all coronaviruses and then rapidly and rationally modified based on any emerging coronavirus derived pathogens.

This is especially important, he explained, considering continuing waves of infections.

For those reasons, the central goal of his study is to develop universal platforms to design vaccine candidates for coronaviruses, including SARS-CoV-2, that are based off altering the molecular details of coronavirus genome replication, transcription and translation.

Like the small molecule drug strategies which have shown very promising results by targeting the way in which these viruses replicate, Mehta envisions developing a universal live attenuated SARS-CoV-2 vaccine platform by engineering highly conserved coronavirus replication and transcription mechanisms.

Because these mechanisms are highly conserved, or identical, his platform will have the potential to be a universal and modular platform to engineer coronavirus vaccine candidates.

“So, we are targeting mechanisms that are identical in all known coronavirus pathogens; this makes it possible for our platform to be potentially modular and universal,” he said. “This is a bit different from current vaccine strategies that target proteins on the surface of the virus, where mutations have now been detected in these proteins.”

Furthermore, Mehta explained, several differences have also been observed in these proteins when compared to other coronavirus pathogens, including the SARS-CoV pathogen from the early 2000s.

“Therefore developing universal vaccine platforms might have implications on both short-term and long-term vaccine strategies to tackle this global challenge of developing vaccines for COVID-19 as well as future coronavirus pathogens,” he said.
 

Head shot of Professor Wilfred van der Donk

Wilfred van der Donk: Trying to stop the virus from entering human cells

If Professor Wilfred van der Donk can stop the virus from entering human cells, it would prevent the COVID-19 virus infection altogether.

Van der Donk, the Richard E. Heckert Endowed Chair in Chemistry, explained how the SARS-CoV-2 virus that causes COVID-19 enters human cells by recognition of a surface receptor called the human acetyl choline esterase 2 (ACE2).

“The SARS-CoV-2 spike protein, so called because it is the protein that is responsible for the ‘spiky’ protrusions that are shown in artistic renditions of the virus, binds to ACE2 in the first step of entry into human cells,” he said. “If this entry can be stopped, virus infection will be prevented.

The molecular structure of the spike protein bound to ACE2 is known, van der Donk said, and the laboratory of Erik Procko in the Department of Biochemistry at Illinois has studied this interaction.

Compounds that mimic the part of the ACE2 protein where the spike protein binds could in principle work as decoys that bind to the virus and prevent it from interacting with ACE2, and that approach to fighting COVID-19 is what the van der Donk and Procko laboratories are exploring together.

“We use so-called lanthipeptides that resemble the part of ACE2 where the spike protein binds,” van der Donk explained. “Lanthipeptides are very stable compounds made in nature and are already used in the food industry to kill food-borne pathogens.”
 

Head shot of Professor Yi Lu

Professor Yi Lu: Developing more accurate virus testing methods

After receiving a National Science Foundation RAPID grant this spring, Yi Lu launched into a COVID-19 project with Lijun Rong, a professor in the Department of Microbiology and Immunology at the University of Illinois at Chicago to develop a new widely-deployable method to more efficiently detect COVID-19. 

The goal is to identify and synthesize DNA aptamers — short, single-stranded DNA molecules that can selectively bind to a target. The aptamers will bind the intact infectious SARS-CoV-2, the virus that causes COVID-19, but not the non-infectious forms or other viruses and interfering species, with high specificity and affinity, explained Lu, the Jay and Ann Schenck Professor of Chemistry.

When the DNA is immobilized into a nanopore, a tiny pore of nanometer size, this method would be less resource intensive than the sensing technique commonly used now, he said, and it would also simplify the testing procedure partly because sample pretreatment would not be needed. And it would also minimize the chance of cross contamination.

“Most importantly, our method addresses a major limitation of current COVID-19 diagnostic tests that are mostly based on detecting viral RNA; they cannot inform whether the virus is infectious or not,” Lu said, “because it has been shown that the presence of viral RNA in specimens does not always correlate with viral transmissibility” 

He emphasized the importance of rapid and accurate detection of the infectious viruses. It provides patients the opportunity to receive proper treatments early on and prevents them from unknowingly spreading the infectious virus to others, Lu explained, and it also eliminates unnecessary quarantine of non-contagious patients and enables assessment of whether surfaces at critical locations, such as hospitals, airports, grocery stores and home, have been properly disinfected. Lu is one of three Nick Holonyak Jr., Micro and Nanotechnology Lab (HMNTL) faculty members that have received RAPID grants, all of which hope to shorten the amount of time it takes to process a COVID-19 test.
 

Head shot of Professor Xing Wang

Professor Xing Wang: Better, faster COVID-19 detection methods

With the support of a National Science Foundation RAPID grant, chemistry professor Xing Wang is working along with Brian Cunningham, a professor in Electrical and Computer Engineering at Illinois, to develop a new sensing paradigm for virus diagnostics that does not require the chemical enzymatic amplification of nucleic acids. This would eliminate the need for temperature control, thermal cycles, viral lysis, nucleic acid purification, or fluorescent dyes in virus testing. Their entire virus sensing process, explained below, is estimated to provide COVID-19 test results in less than 15 minutes.

According to Wang, their COVID-19 detection strategy combines two novel technologies recently developed in the labs of Wang and Cunningham.

First, they are using a designer DNA nanostructure-based technology developed in the Wang group, called Pattern-recognition Enabled Sensing and Therapeutics (PEST) to synthesize a customized DNA “virus net” that can recognize and capture intact SARS-CoV-2 virus particles with high binding avidity and specificity.

Second, the researchers then immobilize “virus net” on a photonic crystal biosensor surface to selectively attach the virus to the biosensor surface.  The captured SARS-CoV-2 virions from patient samples are “imaged” by a new form of biosensor microscopy, developed in the Cunningham group, and called Photonic Resonator Interference Scattering Microscopy (PRISM), which allows users to detect and digitally count virus particles, protein molecules, and a variety of nanoparticles in real time without the use of additional labels or stains.
 

Head shots of Professors Martin Burke and Paul Hergenrother
Professors Martin Burke (left) and Paul Hergenrother

Burke and Hergenrother: SHIELD initiative

Burke is leading the SHIELD initiative to stand-up and strategically deploy rapid and scalable COVID-19 testing, to detect the virus and virus antibodies, in concert with frontier modeling and contact tracing platforms as part of a broad integrated  effort to reopen our Champaign-Urbana community as safely as possible. The program centers on a three-part strategy dubbed Target, TEST, and Tell.

Burke is joined in this effort by a large number of partners from across campus, including chemistry Professor Paul Hergenrother.

A COVID-19 testing facility is being created as a new arm of the Veterinary Diagnostic Lab on campus that already has experience testing for COVID-19 in animals, and it’s combining efforts with other university entities, including the National Center for Supercomputing Applications and the new RokWire digital society, an interdisciplinary team of computer scientists and other experts on campus who are developing a digital operating system for the cities of tomorrow.

Burke said the considerable strengths of the NCSA, the new ROKWire digital society, and an intensive community engagement effort will be collectively interfaced with the data generated from this new lab to mitigate the risk that COVID-19 poses for our Champaign-Urbana community.

COVID-19 Briefing Series: SHIELD: Target, Test, Tell
 

Head shots of Professors Martin Burke and Doug Mitchell
Professors Martin Burke (left) and Doug Mitchell

Burke and Doug Mitchell: Donation of testing components for local and state testing

Two initiatives took shape on campus to provide COVID-19 testing supplies that are in drastically short supply: one was focused on creating liquids necessary to conduct COVID-19 testing and the other was focused on the creation of nasopharyngeal swabs. 

Chemistry’s Martin Burke and Doug Mitchell, Alumni Research Scholar Professor of Chemistry, collaborated with Microbiology’s Chris Brooke to mass produce liquids necessary for COVID-19 testing, including buffered saline and viral transfer media (VTM), an essential mix of buffers, nutrients, and antimicrobials that’s in short supply.

VTM is used to preserve test samples from patients until testing occurs. As faculty with appointments in the Carl R. Woese Institute for Genomic Biology, they were granted laboratory space in the institute to begin producing VTM using base materials from their own research supplies. A pair of laboratory technicians from Burke’s laboratory, Justin Lange and Akanksh Shetty, stepped forward to help, and soon the team was mass producing VTM. That caught the attention of state officials, who asked them to produce enough VTM for 10,000 tests per week. The VTM will be sent to a state laboratory in Springfield, with Illinois Emergency Management Agency reimbursing the university for the direct cost of the product.

As the agreement with the state of Illinois took shape, the Carl R. Woese Institute for Genomic Biology made available six more laboratory spaces, in addition to the one already being used, to scale up VTM production. More than 150,000 tubes of viral transfer media have been delivered to date, which has helped Illinois increase its testing capacity state wide.

“It has been deeply gratifying to see how faculty, staff, and students have stepped up to make it possible for the institute to contribute to this critical effort, from sourcing scarce materials, to facilitating deliveries, to organizing, training, and supervising staff, to actually preparing the VTM,” said Gene Robinson, Swanlund Chair of Entomology and director of the Carl R. Woese Institute for Genomic Biology. “This has been an inspirational team effort fueled by altruism.”

Mitchell said it hasn’t been easy to essentially turn an academic environment into a factory to fight COVID-19, but he is strongly motivated.

“Healthcare workers are those on the front lines of dealing with this disease; however, there is essentially no testing being done on those individuals who are exposed every day to patients with COVID-19,” he said. “How many people have been infected in hospitals and in the community through asymptomatic transmission of the virus? Without widespread testing, we will never know. The amount of testing that has been done thus far is a very far cry from what needs to be performed.”

Brooke said that it’s been stressful to get the testing up and running, but that he feels some satisfaction for making a difference.

“What we’re doing is small,” he added, “compared to the health workers who are actually serving patients on the front lines.”

This collaborative effort produced enough materials for nearly 200,000 coronavirus tests across the state. 

Head shot of Professor Jeffrey Moore

Jeffrey Moore: Mass production of swabs to collect test samples

Meanwhile, another campus team has been spearheading the mass production of nasopharyngeal swabs (also in short supply), which are used to collect test samples from patients’ noses. In collaboration with Carle diagnostic labs, the team reverse-engineered a commercial swab to design and test their own.

The team, which includes Mitchell, Jeffrey Moore, a Stanley O. Ikenberry Chair and professor of chemistry and materials science and engineering, and director of the Beckman Institute for Advanced Science & Technology, and Nancy Sottos, a Swanlund Chair and head of the Department of Materials Science and Engineering, developed a method to create enough swabs that, if validated, could meet a portion of the need in the state of Illinois.

The team also includes Martin Gruebele, James R. Eiszner Endowed Chair in Chemistry and head of the Department of Chemistry, providing oversight as the plan calls for using glassware ovens found in organic chemistry labs in Roger Adams Lab to create the swabs. Mitchell described the process as converting a precursor rod into a viable swab using a hot draw. The key, he said, is to stretch the material in a way that retains rigidity in the handle while allowing for flexibility in the portion that enters the patient’s nose. 

The Beckman Institute is creating a training video which can demonstrate how to create a swab within about 90 seconds. Once the swabs are validated at Carle and the Illinois Department of Public Health, group members and other researchers plan to produce up to 300,000 swabs to help deal with the crisis.  

“We came to the lab to reverse engineer the nasopharyngeal swab with a safe, inexpensive, rapid, scalable method from common laboratory supplies and equipment,” Moore said. “When our initial idea hit a snag, the graduate students put their ingenuity to work and improvised a brilliant solution that checked all the boxes.”

 

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