Scientists turn to COVID-19 research, hoping for quick results to tackle pandemic

Screening scientist Eddie Wehri and CEND executive director Julia Schaletzky at the UC Berkeley Drug Discovery Center, which helps researchers find potential treatments for COVID-19. (Photo courtesy of CEND)

Thanks to a rapid funding scheme launched by wealthy entrepreneurs just six weeks ago, seven COVID-19 research projects at the University of California, Berkeley are getting a cash injection – $2.2 million in total – which could generate new diagnostics and potential treatments for the infection within months.

A diverse group of funders pooled their resources and solicited so-called rapid grant proposals in early April, promising to review them within 48 hours and send the money within weeks, much faster than any other body. funding, public or private. Contributors wanted research ideas that would have a quick turnaround – results within six months – in order to have an impact on the pandemic now.

Anders Näär, professor of metabolic biology at UC Berkeley and vice chair of the Department of Nutritional Sciences and Toxicology, was one of 20 reviewers for what turned out to be a deluge of applications: about 4,000 in all. . The grants covered almost every aspect of the new pandemic disease, from diagnostics to vaccines and treatments.

“I reviewed 350 grants in 36 hours; I slept about four hours in those 36 hours,” he said. “It was quite a challenge.”

So far, Fast Grants, part of Emergent Ventures, a project of George Mason University’s Mercatus Center, has distributed $22 million to around 100 researchers in the United States, Canada, Europe and in Japan.

Like many researchers who applied, Stephen Brohawn, assistant professor of molecular and cellular biology, first heard about the grants on Twitter.

“We had already started working on this project, we had some nice data showing things were looking very promising, and we put it together and heard it in two days,” said Brohawn, who was awarded $100,000 to research drugs. targeting an ion. channel in the membrane of SARS-CoV-2, the virus that causes COVID-19. He teamed up with Diana Bautista and Hillel Adesnik, professors of molecular and cellular biology, who, like Brohawn, study ion channels, which all cells need to function properly.

“It’s possible we could find a therapeutic that would be useful in the short term” as we wait for the development of a vaccine, Brohawn said. “We will pursue this as quickly as possible.”

Eva Harris in the lab

Eva Harris demonstrating the ease of taking a blood sample from a finger prick. She and her colleagues hope to collect blood samples from East Bay residents to assess the prevalence of COVID-19 in the general population. (Photo courtesy of KTVU)

Eva Harris, director of UC Berkeley’s Center for Global Public Health and professor of infectious diseases, was awarded $400,000 for her goal of raising $2 million for a massive effort to verify the infection status of at least 5,000 asymptomatic people in 11 East Bay towns through genetic and antibody testing.

“Our research…will provide much-needed insight into transmission dynamics, the true extent of community spread, and risk factors for infection beyond those tested for COVID-19 in hospitals and clinics,” said said Lisa Barcellos, professor of epidemiology and biostatistics, who is leading the study with Harris.

Patrick Hsu, Assistant Professor of Bioengineering and Fellow of the Innovative Genomics Institute (IGI), has been awarded $300,000 to apply new CRISPR tools he discovered for faster and better diagnosis of COVID infection -19 and potentially new therapies. The research, conducted in collaboration with Jennifer Doudna, executive director of the IGI and researcher at the Howard Hughes Medical Institute, and David Savage, associate professor of molecular and cellular biology, also involves the search for new drug targets using screens CRISPR genetics.

“Normally, we use CRISPR tools to develop new types of gene and cell therapies for the brain and the immune system, and my lab has discovered new CRISPR systems that can target RNA,” he said. declared. “SARS CoV-2 is an RNA virus, so when this pandemic started to grow and California started to shut down, a group of us in the lab thought we might be able to exploit these Cas13 enzymes targeting RNA to develop more sensitive diagnostic tests. this could potentially be done at home or at the point of care.

In search of drugs to fight COVID-19

Näär did not consider his own application, but he was awarded $400,000 to pursue a new idea for treating the viral disease: using antisense oligonucleotides to block virus replication, target the virus’ RNA genome, or , alternatively, RNA in human cells that help make more viruses.

lab worker

In the Harris lab at UC Berkeley. (Photo courtesy of KTVU)

Antisense oligonucleotides are essentially strings of nucleotides – ribonucleic acids – that attach firmly, like molecular Velcro, to a complementary strand of RNA, rendering it unreadable. If that target RNA is a key piece of the virus’s genetic code, or a piece of human RNA that the virus co-opts to make copies of itself, the virus can no longer reproduce.

He will focus on improved antisense tools called nucleic acid-locked antisense oligonucleotides, or LNA ASOs, which he has previously developed to treat cardiovascular disease, obesity, type 2 diabetes and fatty liver disease. His results are so promising that he is looking for funds to start clinical trials, and he thinks ASO LNAs also show great promise against SARS-CoV-2.

“There is tremendous interest in health sciences at UC Berkeley, and that is reflected in these COVID-19 efforts,” Näär said. “I was extremely impressed with the wave of support and interest in Berkeley, which is more or less a basic science institution and not necessarily a biomedical institution.”

Two other UC Berkeley research teams have also received rapid grants to research drugs that inhibit the virus.

Daniel Nomura leads a group of researchers who plan to use innovative chemical biology approaches to develop new therapies against COVID-19. With $500,000, the team, which includes Niren Murthy, professor of bioengineering, and Jamie Cate, professor of chemistry and molecular and cell biology, will search for weaknesses in SARS-CoV-2 proteins that could be exploited by a small molecule, hoping to eliminate the virus.

“We were able to develop very potent inhibitors against the SARS-CoV-2 major cysteine ​​protease (MPro), which is essential for viral replication and also inhibits SARS-CoV-1 and MERS-CoV MPros” , did he declare. . “The goal of this project is to develop a drug against not only COVID-19, but also future coronaviruses.”

Näär, Brohawn and Nomura will rely heavily on UC Berkeley’s new Drug Discovery Center to take potential targets they uncover and toss drugs at them to see if they knock out the virus.

The center was established over the past two years by Julia Schaletzky, executive director of UC Berkeley’s Center for Emerging and Neglected Diseases (CEND) and its Immunotherapeutics and Vaccine Research Institute (IVRI), who had just completed testing start-up before COVID-19. the pandemic hit.

“It was kind of perfect timing that we had done all this work just before, so now we’re getting into testing campaigns and drug discovery campaigns,” she said.

Schaletzky received $300,000 in Fast Grant funding to quickly begin screening more than 1,000 drugs already approved in the United States and Europe to see if anything now available to treat a disease will also work against COVID-19. His collaborator is Sarah Stanley, an associate professor of infectious diseases who normally studies tuberculosis, a highly contagious disease. Tuberculosis bacteria and the new coronavirus can only be handled in a biosafety level 3 (BSL3) laboratory, so she was able to quickly switch to working with SARS-CoV-2.

BSL3 laboratory

Erik van Dis handling SARS-CoV-2 in the BSL3 lab at UC Berkeley. (UC Berkeley photo by Sarah Stanley)

Stanley will infect human and monkey cells with live SARS-CoV-2, against which Schaletzky will test a library of drugs already approved or in clinical trials. Candidate drugs that rescue infected cells will then be tested in Syrian golden hamsters, one of the few animals, other than primates, susceptible to SARS-CoV-2. Stanley received $200,000 from Fast Grants to develop the hamster as a drug screening model and to understand the basic immunology of infection.

Stanley also breeds genetically engineered mice with human-like immune systems in which to test drugs that pass screens.

“I find it super exciting that so many really bright people are entering the virus field,” said Schaletzky, who organizes the annual Bay Area Virus Symposium. The Fast Grant money is just a pot of new funds to support this COVID-19 research (see below).

A particularly absent funder, however, is the federal government. While federal agencies have announced that researchers can apply to reallocate existing funds to COVID-19 research and have pledged new emergency funds for pandemic-focused projects, disbursements have been extremely slow, he said. Schaletzky said. Despite numerous UC Berkeley proposals submitted to the National Institutes of Health since the start of the pandemic, for example, none have been granted.

“Why, in a crisis like this, do we have to raise all the money from philanthropy? How bizarre,” said Schaletzky, who wrote an op-ed in March about the lack of funding. “We gave $58 billion to the airlines alone, no questions asked. But for research, the money just isn’t there. I’m really glad we’re having good fundraisers because otherwise we’d just be sitting there waiting.


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