As the COVID-19 pandemic continues, the development of antiviral drug treatments has become a critical weapon in our arsenal against the virus.
The University of California – National Labs Antiviral Treatments Targeting All Coronaviruses and Key RNA virus, or ATTACK, Consortium, harnesses the research and scientific intelligence needed to treat and prevent the next pandemic.
The group integrates expertise and resources from six University of California Los Angeles campuses, San Diego, Davis, Berkeley, Irvine, and Riverside; two national laboratories, Lawrence Livermore and Sandia; and 13 industrial partners. Adam Godzik and Maurizio Pellecchia of UC Riverside, both professors of biomedical sciences in the School of Medicine, are members of the consortium.
“The structural systems biology group at UCR, which I lead, will analyze and monitor the evolution of targeted pathogens to ensure that drugs under development would be active against new pathogen variants, as well as to identify and assess novel therapeutic targets in emerging viruses using modeling and machine learning/artificial intelligence approaches,” said Godzik, Bruce D. and Nancy B. Varner Endowed Presidential Chair in Cancer Research at UCR.
Pellecchia, holder of the Daniel Hays Chair in Cancer Research at UCR, leads a group working on the design and screening of potential drug compounds.
“We are excited to be part of the ATTACK consortium and support the initiative by collaboratively deploying our unique drug discovery strategies,” he said. “This is an exceptionally exciting opportunity to interact with scientists from diverse backgrounds from various UC campuses and national labs and join forces to prevent the next pandemic.”
According to Brigitte Gomperts, professor of pediatrics and pulmonary medicine at UCLA and center director and PI of a recent ATTACK consortium funding proposal to develop antiviral drugs to treat and prevent future pandemics, putting such expertise under a same roof will help alleviate much of the silos that have plagued the development of past antiviral drugs.
“That’s our ultimate and overall goal,” she said. “We want to prevent and prepare for the next pandemic.”
When the next pandemic arrives is a matter of when, researchers say, not if.
UCLA virologist Vaithilingaraja Arumugaswami, an associate professor of molecular and medical pharmacology at UCLA, has worked on viruses and infectious diseases for years.
“We need a combination of antivirals and vaccines to fight the virus and trigger the pandemic,” Arumugaswami said. “The development of antiviral drugs is crucial.”
To do this, the ATTACK Consortium brings together the best minds in drug discovery and development and actively seeks additional funding opportunities to expand the scope of their work.
“The extraordinary measures of this pandemic have created an opportunity,” Arumugaswami said. “I never expected to see more than 50 of the world’s top researchers from a variety of disciplines coming together to tackle this problem.”
Collaboration and know-how
Recently at the California NanoSystems Institute, or CNSI, at UCLA, these top 50 researchers in antiviral drug development came together in person and virtually to expand the strong research, resource and support collaboration they have generated. together.
“I was impressed with the intelligence in the room and the ability to solve these complex problems and prevent future pandemics,” said David Smith, infectious disease physician, professor of medicine at UCSD and PI of the group. “The ATTACK Consortium brings ideas from the bench to the bedside through motivation, collaboration and trust. We have partners as part of the consortium who can bring ideas and discoveries to the clinic through their expertise and skills. capabilities, allowing us to work at a fast pace.”
The ATTACK consortium meeting allowed new collaborations and experiments to kick off in the short term with a long-term eye on developing the pipeline that exists across UC campuses and national labs.
The group quickly developed an expertly effective pipeline that begins with discovery and ends with highly effective direct-acting antiviral therapies that have passed all of the preclinical tests necessary to enter human trials.
“We picked up the ball and we’re running with it,” Smith said. “We have learned from past pandemics as far back as the HIV virus 40 years ago and from those that have occurred since and we are better at predicting which viruses might arise in the future and the hope of this group is to develop what treatment could be used for them.”
National Laboratory, Industry Resources
The speed of collaboration is underlined by the support of national laboratories and industrial partners. The partner national labs, Lawrence Livermore National Lab and Sandia National Lab, report to the Department of Energy’s National Nuclear Security Administration Laboratories.
The Department of Energy’s 17 National Laboratories address the critical scientific challenges of our time and possess unique instruments and facilities, many of which are found nowhere else in the world. They tackle complex, large-scale research and development challenges with a multidisciplinary approach that emphasizes translating basic science into innovation.
“As partners, National Laboratories have served as the premier institutions for scientific innovation in the United States for more than seventy years,” said Robert Damoiseau, professor of molecular and medical pharmacology and bio- engineering at UCLA and director of the shared molecular screening resource at the university. CNSI at UCLA.
Damoiseau has worked closely with national labs and industry partners on previous collaborations and knew that adding their brains and resources to the ATTACK Consortium would greatly increase the capabilities and strengths of the group.
“National labs have resources and an interest in antiviral drug discovery that adds another dimension to what we can do,” Damoiseau said. “And that allows us, as a public entity, to have a very different, transparent and community-focused approach than other groups, which can impact the public good on a larger scale.”
Felice Lightstone is the Biochemical and Biophysical Systems Group Leader and Associate Program Leader for Medical Countermeasures at Lawrence Livermore National Laboratory.
“National Laboratories not only offer high-performance computing and BSL-3 (biosafety level) clearance for secure agent research,” Lightstone said. “We are creating technologies that can make the drug design process more efficient and effective.”
National labs also link academia and industry, having a long process of collaboration with non-profit organizations and government entities.
“This is cutting-edge research,” Smith said. “With this group, we can fully integrate the drug development process. For example, while we are designing drugs for efficacy, we should also be developing safety profiles for the drug in parallel. If we look at efficacy and safety at the same time, we can simultaneously shorten the time to drug development. »
Research already underway
For the ATTACK Consortium, this cutting-edge research is already underway.
“We took a divide and conquer approach and each contributed their strengths and abilities to ‘ATTACK’ this global health issue, hence the name of the consortium,” said Damoiseau.
For now, the five highly integrated research projects and the four scientific cores are working to achieve the objectives of the consortium. Research projects include:
- Artificial Intelligence and Machine Learning Drug Discovery
- New ultra-high throughput drug screening
- Optimization of drugs for IND studies allowing
- Viral RNA targets
- Viral protease targets
Lawrence Livermore researcher Adam Zemla and UC Riverside’s Godzik are just two researchers collaborating on ATTACK research projects, analyzing the Omicron variant for possible back-to-back mutations.
“There are so many unknowns about what will happen next and so much complexity that is needed to help achieve our goals,” Zemla said. “We are moving forward to have experts in all of these areas that will allow our project to move forward and prepare for the next pandemic.”
A promise of the future
It remains to be seen what will be achieved by the ATTACK Consortium, but as Damoiseau says by its size and motivation, the odds are in their favor, as evidenced by the seventeen peer-reviewed publications by members of the ATTACK Consortium. over the past two months. .
“We’re a conglomerate and one of the largest academic groups tackling this problem and looking for these kinds of solutions,” Damoiseau said. This work is necessary to discover treatments and medicines to treat and prevent future pandemics and protect the health of our global population. If we do, we will be ready.
Indeed, the ATTACK Consortium was able to work very quickly to find new potential therapeutic strategies for the Omicron variant. Team members recently completed characterization of therapeutic nanobodies — a form of antibody — which have activity against Omicron, as well as the previous Delta variant of SARS-CoV-2. The researchers also found an RNA inhibitor that targets Omicron. Both strategies could be fundamental for novel broad-acting SARS-CoV-2 therapies.
About the UC-NL ATTACK Consortium
The ATTACK consortium includes world-class academic researchers who have come together to develop a comprehensive solution for the rapid and rigorous discovery and development of antiviral drugs to help solve the current COVID-19 crisis and prevent next pandemic.
Organized into five key integrated research project areas and four scientific cores, the consortium provides a rigorous pipeline for antiviral drug discovery, identification of specific viral targets and drug optimization with initial work in coronaviruses, l enterovirus D68, dengue virus and Nipah virus.
This press release is a slightly edited version of a UCLA press release written by Nicole Wilkins.