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Animals’ Susceptibility to Coronavirus Subject of U of I Research

The following article highlights research funded through IMCI. The original news release was written by Ralph Bartholdt in University of Idaho Communications and Marketing.

MOSCOW, Idaho — Sept. 17, 2020 — Whether coronavirus can use farm animals or North American bats as intermediate hosts to spread the novel pathogen SARS-CoV2 is being explored by three University of Idaho researchers.

At his lab on the Moscow campus, Paul Rowley, a virologist and assistant professor in the Department of Biological Sciences, is using mammalian cell cultures and a viral agent similar to coronavirus to get to the bottom of the question.

“We already know that humans can infect cats and other animals,” Rowley said. “We’re interested in learning what animals are susceptible and if there’s a risk of SARS-CoV2 jumping into the bat population in North America, or domestic cattle or livestock.”

Aided by a federal grant, Rowley has teamed with U of I Research Assistant Professor Jagdish Patel, a molecular modeling specialist, and James Van Leuven, research assistant professor, to identify animal populations that are likely susceptible to the pandemic.

Ferret farms in Europe this year were shut down and the animals killed because of SARS-CoV2 infections, Rowley said. And civet cats — a weasel-like animal related to the mongoose — were partly responsible for the SARS outbreak of almost 20 years ago.

“Those populations could potentially act as viral reservoirs and could initiate new disease outbreaks,” Rowley said.

Viruses are submicroscopic bundles of genetic material that cannot replicate without first invading a host cell. Once inside a cell, viruses such as SARS-CoV2, the coronavirus responsible for the global pandemic, multiply and can make us sick.

Instead of working on treatments to kill SARS-CoV2, Rowley, Patel and U of I Department of Physics Professor Marty Ytreberg, began last spring to locate cell doors — called receptors — that allow viruses to board and invade a cell.

If the researchers find a way to block receptors that allow SARS-CoV2 to penetrate a cell, they could effectively halt the spread of the virus. Determining the animal receptors that enable SARS-CoV2 cell entry will benefit both human and animal health, Rowley said.

So far, scientists have learned that livestock is not as susceptible to coronavirus as humans, he said.

All-Hands Virtual Poster Session

IMCI is hosting a virtual poster session as part of the GenoPheno All-Hands meeting for the EPSCoR Track-2 project on May 28-29. You are invited to participate.

We are asking each presenter to create a 1-minute YouTube video that briefly introduces your research. A link to these “elevator pitch” videos will be included with the list of posters, so participants can easily decide which poster presentations to attend.

Each participant will be assigned a time slot to present and given a specific Zoom meeting ID.

Complete the following form if you wish to participate.

GenoPheno Virtual Poster SIGN UP

Once you have determined a title, have a YouTube video and a .pdf or .pttx file, please come back to submit those poster details and be assigned a time slot and Zoom meeting ID.

GenoPheno Virtual Poster DETAILS

University of Idaho Works to Develop Cure for COVID-19

University of Idaho Works to Develop Cure for COVID-19

This press release was written by Leigh Cooper in University of Idaho Communications and Marketing. View the original press release here. See the article published in the Idaho Press here. Dr. Marty Ytreberg is the Associate Director of IMCI.

MOSCOW, Idaho — April 20, 2020 —The University of Idaho is working to identify a cure for coronaviruses, including COVID-19.

The Department of Biological Sciences team expects to finish preliminary tests within a year. Researchers will also develop a pipeline for identifying drugs that block viruses from infecting human cells.

The project is funded with $100,000 from a National Science Foundation EPSCoR grant issued to U of I Department of Physics Professor Marty Ytreberg. The EPSCoR funds were provided to determine how amino acid changes modify the way proteins interact with other molecules.

“Funding agencies are giving leeway to researchers with existing grants to shuttle resources toward the COVID pandemic,” Ytreberg said. “We decided this was a good investment, because it has the potential to lead to a therapeutic and fits within the theme of the grant.”

The team includes molecular modeling specialist Jagdish Patel, a research assistant professor; virologist Paul Rowley, an assistant professor; and evolutionary biologist JT Van Leuven, a research assistant professor. The research is being conducted within the Institute for Modeling Collaboration and Innovation, U of I’s multidisciplinary, collaborative research program that houses biomedical research modeling experts.

“The University of Idaho’s research engine has pivoted quickly in the battle against COVID-19,” President Scott Green said. “I’m proud of this team for taking the initiative to help develop a cure for this virus. Their work is rising to the challenge we all face during this difficult time and will help save countless lives in the process.”

The team hopes to create a drug that shields human cells rather than attacks viruses. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus is shaped like a ball with spikes on the surface as shown in widely-used photos. The spike proteins have evolved to dock with a specific protein — called the ACE2 receptor — on the surface of human cells. The attachment of the spike protein to ACE2 begins the infection process by which the virus transfers genetic material to the cell. This genetic material tricks the cell into generating more virus.

Patel and his team want their drug to shield the ACE2 receptor from interacting with the SARS-CoV-2 spike protein.

Drugs targeting human cells, as opposed to viruses, are likely to be effective for a longer period of time, Patel said. Viruses can rapidly evolve at their binding sites to render antiviral drugs ineffective.

The team will improve the known molecules and screen a large library of molecules on computers that might act as inhibitors for SARS-CoV-2. They will test potential inhibitor molecules against a SARS-CoV-2 pseudovirus, a harmless virus with SARS-CoV-2 spike proteins. Promising molecules would then be sent out for testing against the real SARS-CoV-2 virus and subsequently for clinical studies.

“The ACE2 receptor is being used by other coronaviruses as well,” Patel said. “If we find a drug that blocks SARS-CoV-2, the drug should have multiple purposes, protecting us from other coronaviruses like those that cause mild to severe respiratory infection, SARS and NL-63.”

Jagdish Patel, a University of Idaho research assistant professor, is a molecular modeling specialist and among U of I team members working to identify a cure for COVID-19.

Through the process of studying and testing potential inhibitors to combat COVID-19, the team will have developed and refined a multidisciplinary pipeline for antiviral drug development during future outbreaks.

“With the pipeline in place, we will also be able to respond much more quickly to any other disease outbreaks,” Patel said. “We’re designing the pipeline to be flexible so we can adjust to the different challenges each virus poses.”

Within their new pipeline, the researchers will identify antiviral drugs for human receptors other than ACE2, inhibitors that target the virus instead of human cell receptors and inhibitors for other animal viruses.

The awards are made through NSF EPSCoR as part of its Research Infrastructure Improvement (RII) Track-2 investment strategy. RII Track-2 is intended to build national research strength by initiating research collaborations across institutions in two or more EPSCoR jurisdictions. EPSCoR is a program designed to fulfill NSF’s mandate to promote scientific progress nationwide.

This project, “Using biophysical protein models to map genetic variation to phenotypes,” was funded under National Science Foundation grant No. OIA-1736253. The total amount of federal funds for the project is $6 million, which amounts to 100 percent of the total cost of the project.

Patterns of Adaptive Evolution

Project Team: Craig Miller (Co-PI), Holly Wichman (Co-PI), JT Van Leuven, LuAnn Scott

Vaccines are a remarkably effective way to stem the threat posed by infectious diseases. Methods that allow rapid development of vaccines are vital. Synonymous recoding of viral genomes is a recently developed, general, and highly promising strategy for producing live attenuated vaccines. From an antigenic perspective, the method is ideal because it leaves the amino acid sequence of the viral proteins identical to the circulating pathogenic form. A number of viruses have been attenuated by recoding with non-preferred codons or codon pairs, and at least eight studies have shown protective immunization of mice. Despite its demonstrated success, there are fundamental gaps in our knowledge: 1) no effort has been made to compare alternative recoding strategies within the same virus in the same study; 2) several potential methods of synonymous recoding have not been tested at all; 3) the way in which attenuation is affected by the combination of multiple recoded genes is not known; and 4) most importantly, it is unresolved whether viruses attenuated by synonymous recoding are robust to evolutionary recovery.

This proposal tackles these gaps through three Specific Aims.

  • Aim 1: Identify methods of synonymous recoding and associated sequence features that can be used to generate viral genomes with a targeted level of attenuation. This aim includes developing empirical measures of individual codon and codon pair effects on translation rate to guide attenuation. It will also test metrics that have not previously been used for synonymous recoding.
  • Aim 2: Extend models of adaptive evolution to determine if the attenuating effects, within and among genes and transcripts, combine in additive or non-additive ways.
  • Aim 3: Determine if some strategies of attenuation are more robust to recovery than others. This aim will focus on viruses attenuated in multiple regions and by multiple methods, and also determine if some recovery pathways are broadly beneficial.

The project takes advantage of a bacteriophage model system with well-developed tools for genome manipulation and methods for rapid experimental evolution relative to eukaryotic viral systems (i.e., a hundred generations per day at very large population sizes). Achieving these three aims will yield approaches that can be applied to other systems for designing viruses with targeted levels of attenuation that are robust to evolutionary recovery. This research is a critical step toward the long-term goal of achieving a general strategy for fighting infectious diseases by precision design of live vaccines that do not re-evolve virulence when used in humans.