Delicate therapies
The development of antivirals has lagged for a variety of reasons. Until covid-19, companies didn’t have much financial incentive to produce these drugs. Existing antivirals only target 10 viruses, and half of them treat HIV. Chronic infections require longer treatments and therefore bring in more money. “If there isn’t a clear market for a therapeutic, then generally they won’t invest in those types of therapeutics,” says John Bamforth, acting executive director of READDI, a public-private partnership at the United States. University of North Carolina at Chapel Hill founded to develop new antivirals.
There are also a number of scientific obstacles. To inhibit replication, a drug must bind to an essential viral protein or enzyme and block its activity without harming the host cell. But unlike bacteria, viruses rely on the machinery inside the cells they inhabit to copy themselves, so they have few proteins of their own. And even when researchers stumble upon a compound that works, its effectiveness tends to be short-lived because viruses are constantly evolving.
Some researchers, including those at READDI, are working on drugs that target cellular proteins crucial for viral replication. Most antivirals only work on one virus. The hope is that these compounds would be effective against entire families of them. They may also be less likely to elicit resistance.
But new therapies take longer to develop. That’s why the fastest way to get drugs on the shelves is to reuse compounds that have already been approved. They have been tested for safety and there are fewer regulatory hurdles to approving a new use for an existing drug. DNDi is testing a variety of existing compounds in a clinical trial called ANTI-COV. The latest study involves the antiparasitic drug nitazoxanide combined with an inhaled steroid. “The emerging consensus is that you would need a strong antiviral or a combination of antivirals with different mechanisms of action, combined with some kind of anti-inflammatory,” Cohen said.
Biden’s pandemic antiviral program aims to accelerate testing of 19 antivirals already in development. It will also provide around $1 billion to create a drug discovery program to search for compounds that can treat not only SARS-CoV-2 but other viruses as well. The administration also announced that it would purchase up to 1.7 million doses of the antiviral drug molnupiravir from Merck for $1.2 billion, pending regulatory approval. Researchers once considered this drug as a treatment for the flu, but when the pandemic hit, they had to pivot. The compound has already passed phase 2 testing for covid-19.
More than 20 biotech and pharmaceutical companies have come together to form the INTREPID alliance to deliver 25 late-stage novel drug candidates targeting viral pathogens that pose the greatest pandemic risks, including coronaviruses. And the COVID Moonshot is an international consortium of scientists from academia, biotechnology, and the pharmaceutical industry working pro bono or for a fee to develop drugs to inhibit a particular enzyme in SARS-CoV-2. The project is based on crowdfunding and crowdsourcing. Anyone can submit a drug design and see which ones have already been submitted. As of June 28, the project has collected 17,976 molecule designs and synthesized and tested nearly 1,500.
The reward for all these new initiatives may not come for years. But the hope is that when the next pandemic hits, we will be better prepared. “We need to stop this cycle of neglect and then panic,” Cohen says.
Unequal access
Vast inequities have emerged in the deployment of covid vaccines. In the United States and the United Kingdom, more than 45% of the population is vaccinated. In the Democratic Republic of Congo and Chad, less than 0.1% of people have received the vaccine. And where vaccination coverage is low, the virus can increase. “We are seeing spiraling crises in the Indian subcontinent, in Latin America and over the past few weeks in Africa,” Cohen said. These are places that desperately need new therapies, but she fears that new treatments being developed will reach these countries.
This is something READDI thought of. “If we were to license a drug, we would likely include language in the contract regarding global access,” Bamforth says. “We need to make sure these drugs are available to every country in the world, not just the First World that can afford them.”
