As the COVID-19 pandemic continues, the development of antiviral drug treatments has become a critical weapon in our arsenal against the virus.
Harnessing the research and scientific brainpower needed to treat and prevent the next pandemic is the University of California - National Labs Antiviral Treatments Targeting All Coronaviruses and Key RNA viruses, or ATTACK, Consortium.
The group integrates expertise and resources from six University of California campuses at Los Angeles, San Diego, Davis, Berkeley, Irvine and Riverside; two national laboratories, Lawrence Livermore and Sandia; and 13 industry partners. UC Riverside’s Adam Godzik and Maurizio Pellecchia, both professors of biomedical sciences in the School of Medicine, are members of the consortium.
“The UCR structural systems biology group, which I lead, will be analyzing and monitoring evolution of targeted pathogens to assure that drugs being developed would be active against novel pathogenic variants, as well as identify and evaluate novel therapeutic targets in emerging viruses using modeling and machine learning/artificial intelligence approaches,” said Godzik, who holds the Bruce D. and Nancy B. Varner Presidential Endowed Chair in Cancer Research at UCR.
Pellecchia, who holds the Daniel Hays Endowed Chair in Cancer Research at UCR, is leading a group working on the design and screening of potential drug compounds.
“We are thrilled to be part of the ATTACK Consortium and to support the initiative by collaboratively deploying our unique drug discovery strategies,” he said. “It is an exceptionally exciting opportunity to interface with scientists with diverse backgrounds from various UC campuses and the national laboratories and join forces to prevent the next pandemic.”
According to Brigitte Gomperts, professor of pediatrics and pulmonary medicine at UCLA and a 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 one roof will help alleviate much of the silos that have plagued previous antiviral drug development.
“That is our ultimate, overall goal,” she said. “We want to prevent and be prepared for the next pandemic.”
When the next pandemic arrives is a matter of when, according to the researchers, not if.
UCLA virologist, Vaithilingaraja Arumugaswami, an associate professor of molecular and medical pharmacology at UCLA, has been working on viruses and infectious diseases for years.
“We need a combination of antivirals and vaccines to kick the virus and kick the pandemic,” said Arumugaswami. “Antiviral drug development is crucial.”
To do that, the ATTACK Consortium is bringing the top minds across drug discovery and development together and actively seeking additional funding opportunities to expand the scope of their work.
“The extraordinary measures of this pandemic have created an opportunity,” said Arumugaswami. “I never thought I’d see over 50 of the world’s top researchers across a variety of disciplines coming together to attack this problem.”
Collaboration and expertise
On a recent day at the California NanoSystems Institute, or CNSI, at UCLA those 50 top research minds in antiviral drug development gathered in-person and virtually to extend the robust collaboration of research, resources and support they have generated together.
“I was awed by the intelligence in the room and the ability to solve these complex problems and prevent future pandemics,” said David Smith, an infectious diseases physician, professor of medicine at UCSD, and PI for the group. “The ATTACK Consortium is bringing ideas from the bench to the bedside through motivation, collaboration and trust. We have partners as part of the consortium who can move ideas and discoveries to the clinic through their expertise and abilities and that is enabling us to work at a quick pace.”
The ATTACK Consortium meeting has allowed new collaborations and experiments to get off the ground in the short term with a long-term eye to developing the pipeline that exists across the UC campuses and national labs.
The group has quickly developed an expertly efficient pipeline that starts with discovery and ends with highly effective direct acting antiviral therapies that have met all the needed pre-clinical testing to enter human trials.
“We have picked up the ball and we are running with it,” said Smith. “We have learned from past pandemics as far back as the HIV virus 40 years ago and those that have come since and we are better at predicting what viruses may present 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 underscored by support from the national laboratories and industry partners. National lab partners, Lawrence Livermore National Lab and Sandia National Lab, fall under the Department of Energy’s National Nuclear Security Administration Laboratories.
The Energy Department’s 17 national labs tackle the critical scientific challenges of our time and possess unique instruments and facilities, many of which are found nowhere else in the world. They address large-scale, complex research and development challenges with a multidisciplinary approach that places an emphasis on translating basic science to innovation.
“As a partner, the national laboratories have served as leading institutions for scientific innovation in the U.S. for more than seventy years,” said Robert Damoiseaux, professor of molecular and medical pharmacology and bioengineering at UCLA and director of the molecular screening shared resource at the CNSI at UCLA.
Damoiseaux has worked closely with the national laboratories and industry partners on previous collaborations and knew adding their brainpower and resources to the ATTACK Consortium would extend the capabilities and strengths of the group considerably.
“The national labs have resources and interest in antiviral drug discovery that adds another dimension to what we can do,” said Damoiseaux. “And this allows us as a public entity to have a very different approach that is transparent and community focused than other groups, which can impact the public good on a wider scale.”
Felice Lightstone is the group leader of biochemical and biophysical systems and associate program lead for medical counter measures at Lawrence Livermore National Laboratory.
“The national labs offer not only high-performance computing and BSL-3 (Biosafety level) clearance for secure agent research,” said Lightstone. “We make technologies that can make the drug design process more efficient and more effective.”
The national labs also bridge academia and industry, having a long process of collaboration with nonprofits and government entities.
“This is cutting edge research,” said Smith. “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 in parallel safety profiles for the drug. If we are looking at efficacy and safety at the same time, then we can simultaneously shorten the drug development timeline.”
Research already underway
For the ATTACK Consortium, that cutting edge research is already underway.
“We took a divide-and-conquer approach and everyone chipped in their strengths and capabilities to ‘ATTACK’ this global health problem, hence the name of the consortium,” said Damoiseaux.
For now, the five highly integrated research projects and four scientific cores are working to achieve the consortium’s goals. The research projects include:
- Artificial Intelligence and Machine Learning Drug Discovery
- Novel Ultra High Throughput Drug Screening
- Drug Optimization for IND enabling studies
- Viral RNA Targets
- Viral Protease Targets
Adam Zemla, a researcher at Lawrence Livermore, and UC Riverside’s Godzik are just two researchers collaborating on ATTACK research projects, analyzing the Omicron variant for the possible consequential mutations.
“There is so much unknown about what will happen next and so much complexity that is needed to help achieve our goals,” said Zemla. “We are moving forward towards having experts in all these fields which will allow our project to advance and be prepared for the next pandemic.”
A promise for the future
It remains to be seen what will be achieved by the ATTACK Consortium group, yet as Damoiseaux says by sheer size and motivation the odds are in their favor as evidenced by the seventeen peer-reviewed publications from the ATTACK Consortium members just within the last two months.
“We are a conglomerate and one of the biggest academic groups to tackle this problem and go after these types of solutions,” said Damoiseaux. It is necessary to do this work to discover treatments and drugs to treat and prevent future pandemics and protect the health of our global population. If we do this, then 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 finished the characterization of therapeutic nanobodies — a form of antibodies — that have activity against Omicron, as well as the previous Delta variant of SARS-CoV-2. Researchers also found an RNA inhibitor that targets Omicron. Both strategies could be foundational for new broadly acting SARS-CoV-2 therapeutics.
About the UC-NL ATTACK Consortium
The ATTACK Consortium comprises world class academic researchers who have joined together to develop a comprehensive solution for the rapid and rigorous discovery and development of antiviral drugs with the goal to help solve the current COVID-19 crisis and prevent the 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 on coronaviruses, enterovirus D68, dengue virus and Nipah virus.