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.

 

Source: https://www.newyorker.com/

More on the Coronavirus

Facebook, Apple and The War Over Social Media Influencers

In this photo illustration the Apple and Facebook logos are...

Facebook, good. Apple, bad. Facebook, good. Everyone else, bad.

That’s a little reductive but essentially the message put out today by Mark Zuckerberg. Writing on his personal Facebook page, Zuckerberg announced that Facebook won’t take a cut of any earnings that influencers earn on its platform through a growing number of Facebook products until 2023—and when it does start, its fees will be “less than the 30% that Apple and others take.” In addition, Zuckerberg said Facebook would shortly release a helpful little dashboard for influencers to (ostensibly) better manage their earnings and see which companies take a portion of their income.

There’s a lot at stake here. To start, Zuckerberg has increasingly pinned a portion of Facebook’s hopes for future growth on creators and has announced a slew of new initiatives over the past year to encourage influencers to build audiences on Facebook products. Among other things, Facebook plans to roll out audio features with subscription plans, introduce a marketplace where brands and influencers can link up and launch a subscription newsletter service, Bulletin.

Complicating matters is the fact that many other rival companies—TikTok, Snapchat and YouTube, to name only a few—are working on similar things. As well as the fact that Facbeook and Instagram spent many years largely ignoring the influencers on its platforms, while those rivals did a better job at cultivating them and introducing opportunities to earn money off their newfound fame, making those sites a more diserable destination.

To help Facebook stand out, Zuckerberg is willing to do something the others probably aren’t: Let creators earn money on the site without taking a portion of those dollars. Those smaller companies are likely going to be more eager to show investors that these new creator-focused products generate money.

Facebook, by contrast, has the enviable position of . . . not really needing the money. It earned a $9.5 billion profit alone last year and has over $60 billion just in cash. Keeping creators happy and earning money on Facebook keeps them from running off to other sites, taking Facebook users with them. Users have been—and will continue to be—the real moneymakers for Facebook, the people who look at the ads that do make up the majority of the company’s revenue.

The second factor in all this is the burgeoning grudge match between Facebook and Apple—and between Apple and other parts of Big Tech. Apple recently introduced changes to its operating system that will make it harder for Facebook to earn money off ads, part of a larger disagreement between Facebook and Apple over data privacy on the internet.

For its part in the war, Facebook will be doing things like Monday’s announcement: finding ways to paint Apple’s policies as stifling to small businesses on the Web. (Facebook’s timing was blantantly conspicuous, Zuckerberg’s post coming a few hours before Apple begins its much-watched annual developers’ conference.)

Of course, other companies are taking the opportunity to do the same thing to Apple. Less than a month ago, a trial concluded between Apple and Fornite-maker Epic Games over Apple’s allegedly monopolistic grip on large swaths of the internet, a fight also first sparked over fees and a disagreement over who should earn what.

I’m a senior editor at Forbes, where I cover social media, creators and internet culture. In the past, I’ve edited across Forbes magazine and Forbes.com.

Source: Facebook, Apple—And The War Over Social Media Influencers

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Critics:

It’s a bit simplistic, but it’s the message Mark Zuckerberg is conveying today. Writing on his non-public Facebook page, Zuckerberg announced that Facebook will not take any reduction in the profits influencers make on its platform through a number in Facebook product development until 2023, and when it starts, its fees will be “less than the 30% that Apple and others take. In addition, Zuckerberg said Facebook would soon launch a useful little panel so influencers can (apparently) better manage their profits and see which corporations take part in their profits.

The stakes are high here. For starters, Zuckerberg has placed some of Facebook’s hopes for long-term expansion on creators and announced a series of new projects over the next year to inspire influencers to create audiences on Facebook products. Among other things, Facebook. plans to implement audio features with subscription plans, introduce a marketplace where brands and influencers can connect, and launch a subscription newsletter service, Newsletter.

To complicate matters, many other rival corporations (TikTok, Snapchat and YouTube, to name a few) are running similar things, as well as the fact that Facbeook and Instagram have spent many years largely ignoring influencers on their platforms, while rivals have done more of a job cultivating them and introducing opportunities to make money through their newfound fame. , making those sites a more disadvantageous destination.

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First Person Injected With Trial Coronavirus Vaccine In Seattle

A new phase 1 clinical trial of a potential vaccine for the SARS-CoV2 coronavirus began on Monday in Seattle, as the first person to enroll in the trial received the vaccine.

The vaccine, mRNA-1273, was developed by biotechnology company Moderna in combination with researchers from the National Institutes of Health (NIH). The trial is being conducted at Kaiser Permanente Washington Health Research Institute in Seattle.

                           

The phase 1 study aims to test three different doses of the mRNA-1273 vaccine ad hopes to recruit 45 healthy adults for the initial trial. Participants will receive two shots of the vaccine, 28 days apart and will be monitored to evaluate both the safety and immunogenicity of the vaccine. The latter involves seeing how well the vaccine stimulates an immune response to a protein on the SARS-CoV2 coronavirus surface.

The first person to get the vaccine was 43-year old Jennifer Haller from Seattle who said; “I hope that we get to a working vaccine quickly and that we can save lives and people can go back to life as soon as possible,” in an interview with TIME.

                                     

“This study is the first step in the clinical development of an mRNA vaccine against SARS-CoV-2, and we expect it to provide important information about safety and immunogenicity,” said Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna in a press release. He added that Moderna is already working with the FDA and other organizations to prepare for a phase 2 trial, which would involve larger numbers of patients.

The start of the trial comes just 65 days after Chinese authorities sequenced the SARS-CoV2 coronavirus. Just 2 days after that, researchers at the Vaccine Research Center at the NIH finalized the design of the vaccine and began to manufacture it, finishing the first batch on February 7th. On February 24th after analytical testing, the company shipped it to the NIH.

“Finding a safe and effective vaccine to prevent infection with SARS-CoV-2 is an urgent public health priority,” said Anthony S. Fauci, M.D., head of the National Institute of Allergy and Infectious Diseases, at the NIH. “This Phase 1 study, launched in record speed, is an important first step toward achieving that goal,” he added.

The vaccine cannot cause COVID-19 and does not contain the virus as is the case with some other vaccines. Instead it contains a small piece of genetic code called mRNA which scientists have extracted from the virus and then expanded in the laboratory. In this case, the mRNA encodes the viral “spike” protein which is vital for the coronavirus to gain access to human cells. The researchers hope that the vaccine will stimulate the immune system to attack the virus, preventing the development of COVID-19.

                                

Kizzmekia Corbett, Ph.D., of NIAID’s Vaccine Research Center discusses efforts to develop a vaccine against SARS-CoV-2, that causes COVID-19 in an interview conducted Jan. 28, 2020. Credit NIH/NIAID

The mRNA-1723 vaccine was not tested in mice before beginning human clinical trials, an incredibly rare occurrence which has proved controversial. Some experts are insisting that the severity and urgent need of the current situation means this is justified, whereas others are concerned that this could break various ethical and safety standards and put trial participants at greater risk than normal.

Although the design and production of the prospective vaccine was incredibly fast, evaluation of it will take considerable time. All of the participants will be followed for 12 months after the second vaccination to collect the data researchers initially need to figure out whether it is safe and effective.

The study is still enrolling healthy people aged 18-55 in the Seattle area to help test the new vaccine.

Follow me on Twitter. Check out my website.

I am a postdoctoral research scientist focusing on childhood cancers and new, targeted cancer therapies. As a survivor of childhood leukemia myself, I am a determined advocate for research into better, less-toxic cancer treatments and how to reduce the long-term side effects of current drugs. I am an award-winning science communicator and have written for The Times, The Guardian and various cancer-focused outlets. I am also a 2017 TED Fellow, having done my TED talk on cancer survivorship and I regularly do public talks on topics ranging from ‘Why haven’t we cured cancer yet?’ to ‘Cannabis and cancer; hype or hope?’. I am passionate about using social media to communicate science and frequently share pictures and stories from my own laboratory work in real-time on my Twitter account @vickyyyf, alongside commentary about important research breakthroughs. You can find out more about me and how to get in contact via my website drvickyforster.com. All of my articles reflect my personal views and not those of my employer.

Source: First Person Injected With Trial Coronavirus Vaccine In Seattle

Researches are in the clinical trial phase for a COVID-19 vaccine within a “record” number of days. Jennifer Haller, the first human coronavirus vaccine patient, joins MSNBC’s Ari Melber for an exclusive interview, detailing her experience as researches race to find a cure for the coronavirus affecting individuals around the world. Haller tells Melber she will have to do daily logs of her temperature, symptoms, and side effects and will be monitored for 14 months. (This interview is from MSNBC’s “The Beat with Ari Melber, a news show covering politics, law and culture airing nightly at 6pm ET on MSNBC.http://www.thebeatwithari.com). Aired on 03/16/2020. » Subscribe to MSNBC: http://on.msnbc.com/SubscribeTomsnbc MSNBC delivers breaking news, in-depth analysis of politics headlines, as well as commentary and informed perspectives. Find video clips and segments from The Rachel Maddow Show, Morning Joe, Meet the Press Daily, The Beat with Ari Melber, Deadline: White House with Nicolle Wallace, Hardball, All In, Last Word, 11th Hour, and more. Connect with MSNBC Online Visit msnbc.com: http://on.msnbc.com/Readmsnbc Subscribe to MSNBC Newsletter: http://MSNBC.com/NewslettersYouTube Find MSNBC on Facebook: http://on.msnbc.com/Likemsnbc Follow MSNBC on Twitter: http://on.msnbc.com/Followmsnbc Follow MSNBC on Instagram: http://on.msnbc.com/Instamsnbc First Person To Test Coronavirus Vaccine Speaks Out | The Beat With Ari Melber | MSNBC
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