From a new article in the New York Times:
New antiviral drugs are startlingly effective against the coronavirus—if they're taken in time.
n March, 2020, researchers at Emory University published a paper about a molecule called NHC/EIDD-2801. At the time, there were no treatments available for the coronavirus. But NHC/EIDD-2801, the researchers wrote, possessed "potency against multiple coronaviruses," and could become "an effective antiviral against SARS-CoV-2." A few days later, Emory licensed the molecule to Ridgeback Biotherapeutics, a Miami-based biotechnology company which had previously developed a monoclonal antibody for Ebola. Ridgeback partnered with the pharmaceutical giant Merck to accelerate its development.
The Emory researchers named their drug molnupiravir, after Mjölnir—the hammer of Thor. It turns out that this was not hyperbole. Last month, Merck and Ridgeback announced that molnupiravir could reduce by half the chances that a person infected by the coronavirus would need to be hospitalized. The drug was so overwhelmingly effective that an independent committee asked the researchers to stop their Phase III trial early—it would have been unethical to continue giving participants placebos. None of the nearly four hundred patients who received molnupiravir in the trial went on to die, and the drug had no major side effects. On November 4th, the U.K. became the first country to approve molnupiravir; many observers expect that an emergency-use authorization will come from the U.S. Food and Drug Administration in December.
Oral antivirals like molnupiravir could transform the treatment of covid-19, and of the pandemic more generally. Currently, treatments aimed at fighting covid—mainly monoclonal antibodies and antiviral drugs like remdesivir—are given through infusion or injection, usually in clinics or hospitals. By the time people manage to arrange a visit, they are often too sick to receive much benefit. Molnupiravir, however, is a little orange pill. A person might wake up, feel unwell, get a rapid covid test, and head to the pharmacy around the corner to pick up a pack. A full course, which needs to start within five days of the appearance of symptoms, consists of forty pills—four capsules taken twice a day, for five days. Merck is now testing whether molnupiravir can prevent not just hospitalization after infection but also infection after exposure. If that's the case, then the drug might be taken prophylactically—you could get a prescription when someone in your household tests positive, even if you haven't.
Molnupiravir is—and is likely to remain—effective against all the major coronavirus variants. In fact, at least in the lab, it works against any number of RNA viruses besides sars-CoV-2, including Ebola, hepatitis C, R.S.V., and norovirus. Instead of targeting the coronavirus's spike protein, as vaccine-generated antibodies do, molnupiravir attacks the virus's basic replication machinery. The spike protein mutates over time, but the replication machinery is mostly set in stone, and compromising that would make it hard for the virus to evolve resistance. Once it's inside the body, molnupiravir breaks down into a molecule called NHC. As my colleague Matthew Hutson explained, in a piece about antiviral drugs published last year, NHC is similar to cytosine, one of the four "bases" from which viral RNA is constructed; when the coronavirus's RNA begins to copy itself, it slips into cytosine's spot, in a kind of "Freaky Friday" swap. The molecule evades the virus's genetic proofreading mechanisms and wreaks havoc, pairing with other bases, introducing a bevy of errors, and ultimately crashing the system.
With winter approaching, America is entering another precarious moment in the pandemic. Coronavirus cases have spiked in many European countries—including some with higher vaccination rates than the U.S.—and some American hospitals are already starting to buckle under the weight of a new wave. Nearly fifty thousand Americans are currently hospitalized with covid-19. It seems like molnupiravir is arriving just when we need it.
It isn't the only antiviral covid pill, either. A day after the U.K. authorized Merck's drug, Pfizer announced that its antiviral, Paxlovid, was also staggeringly effective at preventing the progression of covid-19 in high-risk patients. The drug, when taken within three days of the onset of symptoms, reduced the risk of hospitalization by nearly ninety per cent. Only three of the nearly four hundred people who took Paxlovid were hospitalized, and no one died; in the placebo group, there were twenty-seven hospitalizations and seven deaths. Paxlovid is administered along with another antiviral medication called ritonavir, which slows the rate at which the former drug is broken down by the body. Like Merck, Pfizer is now examining whether Paxlovid can also be used to prevent infections after an exposure. Results are expected early in 2022. (It's not yet known how much of a difference the drugs will make for vaccinated individuals suffering from breakthrough infections; Merck's and Pfizer's trials included only unvaccinated people with risk factors for severe disease, such as obesity, diabetes, or older age. Vaccinated individuals are already much less likely to be hospitalized or die of covid-19.)
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