How Will the COVID Pills Change the Pandemic?

In 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.

A drug that’s so good at messing with viral RNA has led some to ask whether it messes with human DNA, too. (Merck’s trial excluded pregnant and breast-feeding women, and women of childbearing age had to be on contraceptives.) This is a long-standing concern about antiviral drugs that introduce genomic errors. A recent study suggests that molnupiravir, taken at high doses and for extended periods, can, in fact, introduce mutations into DNA. But, as the biochemist Derek Lowe noted, in a blog post for Science, these findings probably don’t apply directly to the real-world use of molnupiravir in COVID patients. The study was conducted in cells, not live animals or humans.

The cells were exposed to the drug for more than a month; even at the highest doses, it caused fewer mutations than were created by a brief exposure to ultraviolet light. Meanwhile, Merck has run a battery of tests—both in the lab and in animal models—and found no evidence that molnupiravir causes problematic mutations at the dose and duration at which it will be prescribed.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.)

Living in an Age of ExtinctionPaxlovid interrupts the virus’s replication not by messing with its genetic code but by disrupting the way its proteins are constructed. When a virus gets into our cells, its RNA is translated into proteins, which do the virus’s dirty work. But the proteins are first built as long strings called polypeptides; an enzyme called protease then slices them into the fragments from which proteins are assembled.
If you can’t cut the plywood, you can’t build the table, and Paxlovid blunts the blade. Because they employ separate mechanisms to defeat the virus, Paxlovid and molnupiravir could, in theory, be taken together. Some viruses that lead to chronic infections, including H.I.V. and hepatitis C, are treated with drug cocktails to prevent them from evolving resistance against a single line of attack. This approach is less common with respiratory viruses, which don’t generally persist in the body for long periods.
But combination antiviral therapy against the coronavirus could be a subject of study in the coming months, especially among immunocompromised patients, in whom the virus often lingers, allowing it the time and opportunity to generate mutations.

Merck will be producing a lot of molnupiravir. John McGrath, the company’s senior vice-president of manufacturing, told me that Merck began bolstering its manufacturing capacity long before the Phase III trial confirmed how well the drug worked. Normally, a company assesses demand for a product, then brings plants online slowly. For molnupiravir, Merck has already set up seventeen plants in eight countries across three continents. It now has the capacity to produce ten million courses of treatment by the end of this year, and at least another twenty million next year.

It expects molnupiravir to generate five to seven billion dollars in revenue by the end of 2022.How much will all these pills soften the looming winter surge? As has been true throughout the pandemic, the answer depends on many factors beyond their effectiveness. The F.D.A. could authorize molnupiravir within weeks, and Paxlovid soon afterward. But medications only work if they make their way into the body. Timing is critical. The drugs should be taken immediately after symptoms start—ideally, within three to five days. Whether people can benefit from them depends partly on the public-health infrastructure where they live. In Europe, rapid at-home COVID tests are widely available.

Twenty months into the pandemic, this is not the case in much of the U.S., and many Americans also lack ready access to affordable testing labs that can process PCR results quickly.Consider one likely scenario. On Monday, a man feels tired but thinks little of it. On Tuesday, he wakes up with a headache and, in the afternoon, develops a fever. He schedules a COVID test for the following morning. Two days later, he receives an e-mail informing him that he has tested positive. By now, it’s Friday afternoon. He calls his doctor’s office; someone picks up and asks the on-call physician to write a prescription. The man rushes to the pharmacy to get the drug within the five-day symptom-to-pill window.

Envision how the week might have unfolded for someone who’s uninsured, elderly, isolated, homeless, or food insecure, or who doesn’t speak English. Taking full advantage of the new drugs will require vigilance, energy, and access.Antivirals could be especially valuable in places like Africa, where only six per cent of the population is fully vaccinated. As they did with the vaccines, wealthy countries, including the U.S. and the U.K., have already locked in huge contracts for the pills; still, Merck has taken steps to expand access to the developing world.

It recently granted royalty-free licenses to the Medicines Patent Pool, a U.N.-backed nonprofit, which will allow manufacturers to produce generic versions of the drug for more than a hundred low- and middle-income countries. (Pfizer has reached a similar agreement with the Patent Pool; the company also announced that it will forgo royalties for Paxlovid in low-income countries, both during and after the pandemic.) As a result, a full course of molnupiravir could cost as little as twenty dollars in developing countries, compared with around seven hundred in the U.S. “Our goal was to bring this product to high-, middle-, and low-income countries at fundamentally the same time,” Paul Schaper, Merck’s executive director of global pharmaceutical policy, told me.

More than fifty companies around the world have already contacted the Patent Pool to obtain a sublicense to produce the drug, and the Gates Foundation has pledged a hundred and twenty million dollars to support generic-drug makers. Charles Gore, the Patent Pool’s executive director, recently said that, “for large parts of the world that have not got good vaccine coverage, this is really a godsend.” Of course, the same challenges of testing and distribution will apply everywhere.

Last spring, as a doctor caring for COVID patients, I was often dismayed by how little we had to offer. We tried hydroxychloroquine, blood thinners, and various oxygen-delivery devices and ventilator maneuvers; mostly, we watched as patients got better or got worse on their own. In the evenings, as I walked the city’s deserted streets, I often asked myself what kinds of treatment I wished we had. The best thing, I thought, would be a pill that people could take at home, shortly after infection, to halt the cascade of biological processes that sends them to the hospital, the I.C.U., or worse.

We will soon have not one but two such treatments. Outside of the vaccines, the new antiviral drugs are the most important pharmacologic advance of the pandemic. As the coronavirus becomes endemic, we’ll need additional tools to treat the inevitable infections that will continue to strike both vaccinated and unvaccinated people. These drugs will do that, reducing the damage that the coronavirus can inflict and, possibly, cordoning off avenues through which it can spread. Still, insuring that they are meaningfully and equitably used will require strength in the areas in which the U.S. has struggled: early and accessible testing; communication and coördination across health-care providers; fighting misinformation and building trust in rapid scientific advances. Just as vaccines don’t help without shots in arms, antivirals can’t work without pills in people.



More on the Coronavirus

Why Most Modern Online Fraud Prevention Methods Are Falling Short


It was recently reported that new account fraud went up 28% in 2019 compared to 2018 global reports, and more than 100% over 2014 levels. As cybercriminals fine-tune their impersonation efforts, it’s getting more difficult for modern enterprises to distinguish between high-risk and low-risk users — and this will only continue thanks to large-scale data breaches, the evolution of the dark web and the looming threat of identity theft. Unfortunately, traditional authentication methods like passwords, knowledge-based authentication (KBA) and SMS-based two-factor authentication (2FA) can easily be spoofed as the result of the never-ending data breaches that we read about every day.

Just a couple months ago, an unsecured database on the dark web left the personal information of more than 267 million Facebook users, mostly in the U.S., exposed. This type of breach is not only a nightmare for the consumers impacted but also for businesses. When over 190,000 websites are Facebook Login Button customers and almost 40,000 live websites use the Facebook Login Button, a hacker can easily gain access to a multitude of connected accounts by simply having access to a user’s Facebook profile. This particular breach exposed Facebook profiles, as well as email addresses, meaning all fraudsters need to do is look for a consumer’s exposed passwords in a disconnected breach in order to have a good chance at gaining access to their Facebook account and subsequent connected accounts (since 50% of Americans recycle passwords across multiple websites).

Traditional methods like SMS-based 2FA and simple password authentication aren’t the only forms of authentication proving inadequate. Methods like fingerprint scanning have also come up short in recent months, proving hackable with little effort. Digital fingerprints are being sold in the Richlogs Marketplace (dark web) according to a recent report from IntSights. The report reveals that digital fingerprints which include the full fingerprinting of a user’s web browser and computer characteristics, allows an attacker to almost flawlessly impersonate the victim.

It was recently reported that the fingerprint reader on Samsung’s flagship S10 and Note10 smartphones can be spoofed with a $3 screen protector. Unfortunately, this means any person can unlock the device and access its data and any other apps opened by the fingerprint-based biometric security. Smartphone manufacturers have been implementing advanced features for users to secure their devices, using fingerprint readers, face mapping and even sensors that map out the veins in the palm of your hand, but device-centric approaches like fingerprint sensors are inherently problematic.

The biggest issue is that these fingerprint sensors are easily duped and cannot be relied on for commercial authentication use cases, but this approach also suffers from several other limitations. Multiple people can register their fingerprints on the same device, which means it’s unclear which family member was behind a given commercial transaction. Also, if the device is lost or stolen, the ability to recover access to their online accounts is challenging. Finally, device-centric unlocking functionality, such as the Samsung fingerprint scan, is also limited in terms of establishing someone’s actual digital identity for on-device purchases (i.e., users cannot use their fingerprint scans to make purchases from their desktop computer).

For any organization looking for enterprise-grade security, spoof-proof detection and cross-device support, sophisticated face-based authentication is inherently superior to fingerprint-based, SMS-based 2FA and simple password methodologies. Certain cloud-based approaches can leverage the 3D face map of a user’s face to alleviate some of the shortcomings of fingerprint-only authentication methods. Features like certified liveness detection add another layer of protection, rendering the solution practically dupe-proof. These options create a digital chain of trust to a unique user and can be used across devices. This will prove increasingly valuable with the rise of advanced fraud strategies like account takeovers, identity theft and deepfake technologies.

Philipp facilitates Jumio’s product strategy and, with his team, turns visions into products. Prior to Jumio, Philipp was responsible for paysafecard, Europe’s most popular prepaid solution for online purchases.



The nature of payments fraud requires real-time solutions designed to detect and prevent fraud before it happens. Learn what is required to thwart fraud and how UP Payments Risk Management solutions can put you in control of managing risk. Learn more: http://www.aciworldwide/paymentsrisk Commerce and banking channels are multiplying and providing consumers more ways to transact than ever before. From physical channels, like credit, debit and pre-paid cards; checks; ATMs and point-of-sale terminals; to digital channels like ACH, wire, internet, telephone, mobile devices and crypto-currencies. Consumers, businesses, merchants and financial institutions all benefit from anytime, anywhere commerce…but…there’s a dark side. Sophisticated fraud threats are multiplying even faster: malware and Trojans; account takeover and identity theft; credit abuse and bust-out scams; ACH and wire fraud; data breaches; money laundering and employee fraud. In fact, a single data breach can compromise tens of millions of account holders in a matter of seconds.
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