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K-State veterinary faculty target new ways to confront COVID-19

Thursday, May 14, 2020

 

 

MANHATTAN — Scientific work continues in the College of Veterinary Medicine at Kansas State University to better understand and confront the virus that causes the COVID-19 disease.

Faculty, staff, students and postdocs in the college are utilizing their respective areas of expertise to explore different aspects of the novel coronavirus, which reached pandemic levels this spring.

"Our work ranges from physical protection from the virus to the creation of new diagnostics for detection of the virus and serology testing to detect antibodies," said Derek Mosier, head of the diagnostic medicine and pathobiology department. "Our faculty are also working to develop new therapeutics and vaccines. Plus, we have faculty who are conducting detailed studies on the pathogenesis and features of the virus. The more we understand, the better we will be able to control the virus."

A pair of researchers in the diagnostic medicine department recently licensed a technology that may lead to the production of an antiviral drug to treat coronaviruses and noroviruses. Yungeong Kim and Kyeong-Ok "KC" Chang, virologists at K-State, collaborated with William Groutas, a medicinal chemist at Wichita State University. Jointly, they have been using National Institutes of Health grants to work on human norovirus therapeutics. They recently received an additional $3.7 million grant to develop antiviral drugs to treat Middle East respiratory syndrome, better known as MERS human coronavirus. Their work extends to other human viruses that have a similar viral protease, such as rhinoviruses and the newly emerged human coronavirus causing COVID-19.

No antiviral drugs are yet available for human norovirus or coronaviruses, which include SARS, MERS and SARS-CoV-2, the virus that causes COVID-19, but this could change as a result of the license agreement between K-State and Cocrystal Pharma Inc., a clinical stage biotechnology company that develops novel antiviral therapeutics. So far, Chang and Kim have agreements with Cocrystal for multiple therapeutic candidates. The company intends to pursue research and development of theses antiviral compounds, including preclinical and clinical development.

Another K-State researcher and professor, Waithaka Mwangi, has worked with his team to develop three patent-pending experimental immunogens to be evaluated for the ability to induce protection against SARS-CoV-2. Two candidates are designed for eliciting mucosal immunity through intranasal delivery — live-vectored replicons or live-vectored viral nucleic acid — and one is for parenteral immunization — a recombinant protein.

"My lab is scaling up these experimental immunogens in readiness for safety, immunogenicity and protective efficacy testing," Mwangi said.

Kansas State University has signed a nonclinical evaluation agreement with the National Institute of Allergy and Infectious Diseases for the materials to be evaluated.

"We are also working with Dr. Juergen Richt to test the materials at K-State's Biosecurity Research Institute," Mwangi said. "Plus, we are working on generation of therapeutic humanized-neutralizing antibodies. We hope these efforts will help produce a robust intervention against COVID-19."

Richt, a Regents distinguished professor and KBA eminent scholar, is director of the Center of Excellence for Emerging Animal Diseases, or CEEZAD, at K-State.

K-State's Molecular Research and Development team, a part of the Kansas State Veterinary Diagnostic Laboratory, has been working on a multiplex real-time PCR assay — a widely used molecular biology method — for faster detection of the SARS-CoV-2 virus.

"The current CDC-recommended protocol involves three molecular targets that are tested individually," said Jianfa Bai, professor and director of the team. "This means each sample requires three PCR reactions. The multiplex real-time PCR assay developed by the Molecular Research and Development team uses a single PCR reaction for each sample."

Bai said preliminary data generated using a plasmid control and an RNA sample extracted from a SARS-CoV-2 isolate indicated that the multiplex assay has similar analytical sensitivity but better linearity, and it has better repeatability on low concentration samples, as compared to the CDC assay.

"The multiplex assay is under validation with a number of positive and negative samples from human patients," Bai said. "An emergency use authorization application has been filed with the FDA for the assay, which will speed up the detection process three times that of the CDC protocol."

Roman Pogranichniy, an associate professor of virology, said team members in the Kansas State Veterinary Diagnostic Lab led by Jamie Henningson are working with Richt on developing diagnostic assays for SARS2-CoV-2 to detect antibodies and virus and to understand the virus's epidemiology and pathogenesis better.

Richt said CEEZAD is working to develop preclinical models and diagnostics, as well as treatments and subunit vaccines, that will be effective against COVID-19. This work will be conducted at K-State's Biosecurity Research Institute, the only facility on campus in which work with the infectious SARS-CoV-2 can be performed.

"Researchers at K-State have access to one of the nation’s premier biosafety laboratories, the BRI, where research on noro- and coronaviruses can be done safely," said Peter Dorhout, vice president for research. "This facility is an investment by the state and the university. The BRI professional staff also train the next generations of biosafety and biosecurity researchers who will discover the vaccines and treatments of not just the human and animal diseases we face today, but those that will emerge in the future."

The therapeutic and vaccine research is taking place in collaboration with various academic and industry partners. Richt was recently appointed to an ad hoc expert group established by the World Health Organization. The WHO is tasking the group to develop preclinical models of COVID-19 that can be used for the evaluation of vaccines and therapeutics against the disease.

Although reports on the effects of COVID-19 have to date been focused on humans, there have been recent reports that the virus has been transmitted from humans to dogs and cats, and also to large cats in zoos. But Richt said there is currently no information that suggests that pets might be a source of infection for people with the coronavirus that causes COVID-19.

"That is most likely due to reverse zoonoses, meaning COVID-19 human patients transmitted it to the companion animals," Richt said. "CEEZAD's effort is designed to marshal the full range of the center's research expertise against COVID-19. CEEZAD is fortunate to have such dedicated employees with a wide array of expertise in infectious diseases."