COVID cases are surging again in much of the U.S. as the Delta variant takes hold among unvaccinated populations. Antiviral pills given early in the course of infection to prevent severe COVID symptoms and hospitalizations are still lacking, but a new Biden administration effort hopes to change that. The Antiviral Program for Pandemics (APP) is spending more than $3 billion to support research on drugs not just for coronaviruses but also for other viruses with pandemic potential.

Scientific American spoke with Anthony Fauci, long-time director of the National Institute of Allergy and Infectious Diseases and chief medical adviser to President Joe Biden, about his hopes for the APP, the government’s ongoing efforts to boost immunizations in areas with low vaccination rates and what keeps him up at night.

[An edited transcript of the interview follows.]

What are the goals of the Antiviral Program for Pandemics?

There are two components to the program: accelerating clinical testing of promising antivirals that are already in various stages of the development pipeline and expanding the basic science and knowledge needed to discover new antiviral medicines. The primary mover is COVID. But if the APP is successful—and I believe it will be—then it can be directed at any virus of pandemic potential. It will require us to develop the sorts of strong public-private partnerships that allowed us to successfully develop antivirals for HIV and hepatitis C. The important thing to remember is that if you can block an acute viral pathogen in the early stage of infection, then you can avoid progression to the advanced stage of disease.

Can you say anything about which drugs are being considered now?

There are a few drugs that are out there. For instance, a protease inhibitor from Pfizer [currently known as PF-07321332], a drug called molnupiravir from Merck and a drug from Atea Pharmaceuticals [AT-527]. The purpose of the APP is to develop a more robust pipeline.

COVID antivirals work most effectively during the first week or so of infection. Doesn’t that create logistic hurdles for treatment?

That is absolutely correct. You have to give the drugs quickly, during the acute stage of disease, which is a different paradigm than how we treat HIV and hepatitis C, which are both chronic infections. The seven-day window might be a bit more challenging from a strategic standpoint. That is why we are also developing specific and sensitive COVID diagnostic tests, so you know what you’re dealing with and can then quickly and effectively treat people.

What about variants such as Delta? Could they make the drugs less effective over time?

Obviously you have to be concerned that variants might be problematic for antivirals, just as they [may be] for vaccines and monoclonal antibodies. But what we’re aiming at with these drugs are also components of the virus that are critical for replication, which may not be subverted by variants. This is also why we need more than a single drug—which is the same approach we used with HIV when one drug ultimately turned out not to be as effective as multiple drugs in combination. Moreover, as you correctly pointed out, viruses of pandemic potential usually cause acute infections. And because you only need to treat people for relatively short durations, the induction of mutations that would limit the effects of the drugs might not be as likely as when you’re treating people for literally an entire lifetime.

The Biden administration fell short of its goal to at least partially vaccinate 70 percent of the U.S. population by July 4. What can be done about vaccine refusal—a major roadblock to achieving herd immunity?

Even though our [vaccination goal] wasn’t reached, we never intended to stop pushing to get more people vaccinated well beyond the Fourth. So, we're doing everything we can to make vaccines easily available and make sure that people—especially young people—are listening to trusted messengers. We’re working with local community leaders, and we have the COVID-19 Community Corps initiative. We have mobile units for ease of vaccination. We’re doing our very best to get people who haven’t been vaccinated to seriously consider how important it is for themselves, the safety of their families and their community responsibility to put an end to this pandemic. And the way you put an end to this pandemic is by getting as many people vaccinated as possible.

What are you watching out for as society opens up and people try to get back to normal life?

We need to do good surveillance to make sure that we’re not having blips of infection, particularly in the states, cities and counties with low vaccination rates. We have the tools now to effectively suppress the spread of SARS-CoV-2 in this country. And unfortunately, there’s a degree of disparity in the willingness of people in different parts of the country to get vaccinated. And so we have to watch for regional surges in these areas.

Are you getting enough sleep these days?

No [laughs]! Unfortunately, I’m not.