Nirmatrelvir/Ritonavir

On Tuesday, drug discoverer and biotech entrepreneur Alpha Lee told scientists at a chemistry meeting about a new molecule to combat the Zika virus. There are no treatments designed to stop the mosquito-borne infection, which can cause birth defects. After three years of work, Lee and a team of collaborators had made a compound that shut down an enzyme that’s essential for Zika virus replication. But his excitement was short-lived. After the conference session ended, Lee checked his email and saw that the $67 million federal funding supporting the work and several other antiviral programs had been terminated. “The end of the pandemic provides cause to terminate COVID-related grant funds. These grant funds were issued for a limited purpose: to ameliorate the effects of the pandemic. Now that the pandemic is over, the grant funds are no longer necessary,” said the email, which was reviewed by Endpoints News . Zika and Covid have nothing to do with one another. But Lee is one of more than a dozen researchers who told Endpoints that their funding from the National Institutes of Health was cut off as part of the Trump administration’s efforts to stop research on Covid-19 and the virus that causes it, SARS-CoV-2. Some of those researchers were finding ways to make vaccines that could induce sweeping protection against many kinds of coronaviruses. Others had similar efforts focused on antivirals. Yet in many cases, including Lee’s, the research went far beyond the recent pandemic and focused on ways to combat more than a dozen deadly viruses with pandemic potential, many of which have no good treatments. “This was never about Covid. This is about being prepared for the next viral pandemic, which is going to come, we all know it,” said Norbert Bischofberger, a former Gilead Sciences executive who served as an unpaid advisor to a group from the University of California, San Francisco, whose final two years of a $67 million grant were also cut off. While most of the terminated research was spearheaded by academic labs, several of them were working closely with drug companies on the programs. Lee is cofounder and chief scientific officer of a small biotech startup called PostEra. Other labs in the program were working with bigger pharma companies including Johnson & Johnson, Merck, Novartis and Roche. The cuts jeopardize the drugs they were working on, many of which would only become profitable during a pandemic. (While aspects of the research cuts have been reported earlier this week, Endpoints is the first to report their ties to industry drug development efforts.) “I don’t know what to do with these programs,” said Nevan Krogan, a biologist at UCSF whose funding to develop new antivirals was cut. “If these were cancer drugs, pharma would be all over this, because they can make money, right? But they can’t make money on this unless there’s a pandemic.” Lee and Krogan were both funded through a $577 million award from the National Institutes of Health in 2022 to establish nine Antiviral Drug Discovery (AViDD) centers across the country. The goal for each center was to work on at least one new drug to help protect against future coronavirus outbreaks and at least one drug targeting another viral family with pandemic potential. The nine AViDD centers have been even more productive than hoped. They’ve made leads on dozens of potential drugs against at least 18 viruses, including an enterovirus that some scientists have warned could become “airborne polio,” and the Middle East Respiratory Syndrome (MERS) coronavirus, which has a fatality rate of about 30%. “The goal is not just to create knowledge. The goal was to develop products that could really have an impact on protecting human health.” said David Perlin, chief scientific officer of the Hackensack Center for Discovery and Innovation in New Jersey, who co-led an AViDD center focused on making antivirals for several diseases transmitted by mosquitos, including chikungunya and yellow fever. Perlin’s group also worked with Merck on a pan-coronavirus pill that targeted the viral protease, the same target of Pfizer’s drug Paxlovid. The new compound could be an improvement because it doesn’t require the coadministration of an HIV antiviral called ritonavir used to prevent the rapid breakdown of the coronavirus-targeting portion of the drug, called nirmatrelvir. Ritonavir is responsible for some of Paxlovid’s side effects and its interactions with other drugs restricts the patients who can get it. More importantly, the new drug might protect against coronaviruses that have yet to cause a pandemic. Perlin said that it “would be valuable in the Strategic National Stockpile as a way to prevent what we saw with COVID-19, where we had essentially no countermeasures.” Three drug companies — Gilead, Merck and Pfizer — were only able to quickly develop antivirals for Covid during the pandemic because of earlier work on those molecules. When it became clear that the drugs might work against SARS-CoV-2, the companies dusted them off and quickly moved into clinical studies. But all three of those drugs were far from perfect and left room for improvements. Another two years of funding would have supported the preclinical safety studies needed to get the new pan-coronavirus inhibitor ready to test in humans, Perlin said. Merck didn’t respond to a request for comment about the drug’s future. Perlin described his AViDD center as a network of 200 people that formed “a real drug discovery enterprise for rapid response, no matter the threat.” But with the funding pulled, Perlin said that many of the scientists involved will have to find new jobs. Leaders from other AViDD centers also said they will have to make layoffs. “It clearly makes us more vulnerable,” Perlin said. “When you dismantle infrastructures, you have to reassemble them, and that takes time. That means your response to the next threat is just going to be that much slower and more difficult. And there will be casualties.” Funding for AViDD centers was originally supposed to run through April 2027. The future of the programs was already called into question once in late 2023 when the NIH, under the Biden administration, informed centers that the funding for the final two years was gone. Many centers began saving to focus on their best programs and access unspent money through the NIH’s no-cost extension procedure, allowing researchers to stretch out a grant’s timeline by dipping into unused funds. But now that money has been cut off as well. An NIH spokesperson did not respond to questions about why research grants on viruses beyond SARS-CoV-2 were included in the Covid cuts. But they shared a statement saying that the agency “is taking action to terminate research funding that is not aligned with NIH and HHS priorities.” At UCSF, Krogan’s AViDD center has also advanced inhibitors targeting four different coronavirus proteins into IND-enabling studies. One of its more exploratory efforts was focused on how to develop drugs that directly target viral RNA, instead of viral proteins. “If it works, it will have an impact on any RNA virus,” Krogan said. “They made a huge amount of progress,” said Bischofberger, who advised the group. “It’s not that industry couldn’t do this. But you can’t really justify spending public investors’ money on something that is hypothetical in the future,” Bischofberger added. “And startup companies will never get any funding for this kind of work, because venture capitalists will say where’s my return on investment and you may never get one.” Krogan said his group has been in close contact with Roche, which has an advisory role in the programs, but has not made any formal commitment to develop the drugs. A company spokesperson said that “Roche remains committed to advancing research and developing innovative antiviral medicines to address both current and emerging viral threats.” Other AViDD centers were also partnering with drug companies on a variety of antivirals. Johnson & Johnson was working with the University of North Carolina at Chapel Hill on drugs for flaviviruses like West Nile virus and dengue fever. The company, which downsized its infectious disease unit in 2023, did not respond to questions about the future of the programs. Novartis was working with The University of Texas Medical Branch (UTMB) on antivirals against flaviviruses, henipaviruses, and coronaviruses. UTMB researcher Vineet Menachery told Endpoints the group has stopped work on the projects due to funding cuts but “are hoping for reversal of this decision.” A Novartis spokesperson said the company remains “committed to our antiviral work and are evaluating options for the program.” With three separate coronavirus outbreaks this century, many scientists say a fourth is inevitable. One of the best ways to prepare is to make better vaccines. But Duan Wesemann, an immunologist at Mass General Brigham, told Endpoints that his $7.8 million grant that could help make vaccines with broader immunity was cut. “The rationale given was that ‘the pandemic is over,’ but the scientific questions are not,” Wesemann said in an email. “Terminating funding like this not only halts scientific progress—it potentially sets us back years in understanding how to design next-generation vaccines or predict immune durability.” Likewise, Theodora Hatziioannou, a scientist at Rockefeller University, was part of a team trying to develop a shot that could trigger broadly-neutralizing antibodies against coronaviruses yet unseen. Cutting this research now leaves the country, and the world, more vulnerable, Hatziioannou said, a fear echoed by several other researchers Endpoints interviewed. “People will be screwed,” Hatziioannou said. “You can cut all of this and the immediate effects will be negligible. The effects are going to appear in 5 to 10 years. People already forget what happened in the beginning of the Covid epidemic. The hospitals were full of people, trucks were carrying out bodies. This can happen again, and we will be less well prepared for it, and people will die.” Editor’s note: This article was updated to correct Alpha Lee’s title to chief scientific officer.