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

Exploring Nanotechnology & The Future of Renewable Energy

Imagine a future where every home, office or building is painted with solar panels and its bricks operate as batteries thanks to nanotechnology. There’s a lot of promise, but what is nanotechnology? And is it more science fiction than fact?

When you hear the term nanotech, chances are some sci-fi book or movie pops into your head, where they used the term to explain away some technological wonder or advancement. “Don’t worry about that, it’s nanotech!” It’s become a deus ex machina for science fiction writers.

But what we’re starting to see is that nanotechnology is responsible for great advances in physics, biology, chemistry, engineering and material science. It’s responsible for the new age of modern technology that will help civilization reach for the stars and more.

Nanotechnology refers to our ability to study and engineer technologies at a nanoscale, which is the range from 1 to 100 nanometers. That begs the question, “how small is a nanometer?” Well, if I tell you “A nanometer is one billionth of a meter … or one millionth of a millimeter” I don’t think that really clears things up. I don’t know about you, but my brain breaks trying to think about that scale. So, let’s try to put it in perspective: a human hair is around 75,000 nanometers wide – and remember, the range for nanoscale is 1 to 100 nanometers. Still not doing it for you? Let’s flip it around. Imagine a marble measures 1 nanometer. In comparison to that, the Earth would measure about one meter in diameter.1 Let that sink in for a minute… a marble compared to the size of our entire planet … that’s 1 nanometer compared to 1 meter.

Given how mind-boggling these scales are, we definitely have to give credit to the father of nanotechnology, Physicist Richard Feynman. It all started with the American Physical Society meeting held at the California Institute of Technology on December 29, 1959. Feynman gave a talk titled “There’s Plenty of Room at the Bottom,” where he speculated about being able to construct machines down to the molecular level — and the concept behind nanotechnology was born. It wasn’t until 1974 that the term “nanotechnology” was coined by Professor Norio Taniguchi, while he worked on ultraprecision machining.

As he put it: “nanotechnology mainly consists of the processing of separation, consolidation, and deformation of materials by one atom or one molecule.” We had the concept, then the term, but it wasn’t until 1981 that this theory became a reality with the development of a scanning tunneling microscope that helped scientist actually see atoms individually. Gerd Binnig and Heinrich Rohrer developed the microscope at IBM Zurich Research Laboratories in Switzerland and were later awarded the Nobel Prize in physics in 1986. That major achievement was followed by the Atomic Force Microscope in 1985, which had the distinct advantage of imaging on almost all surfaces, including biological samples, glass, composites, and ceramics. This would prove to be a major turning point.

With the advent of nanotechnology, scientists were now able to manipulate individual atoms. And that takes us into the realm of quantum mechanics, which is the science behind how matter behaves in atomic and subatomic scale. Thankfully, that’s out of scope for this video since that breaks my brain even more, but basically materials at this scale tend to behave differently and exhibit distinctive chemical and physical properties. Scientists were keen to learn and exploit this attribute to craft materials at nanoscale.

Since 1981, we’ve come forward leaps and bounds in the field of Nanotech. There’s so much that I could cover, but in the interest of time, I’ve picked two categories of examples that are helping to make what seemed like science fiction into science fact for our future. But I’d love to hear in the comments if there are any topics or examples you’d like to see covered in a future video.

Solar

The first category is one that I talk about a lot: solar. Nanotechnology is leading the charge for solar energy. Most silicon based solar panels, which accounts for about 95% of commercial solar, utilize nanoscale processes for manufacturing. Some are multi-junction solar cells, which layer different solar technologies to broaden the wavelengths of light that are captured and converted into energy. This layer cake of solar cell technologies are measured in nanometers. Thinner than a width of a human hair. But it’s the next generation of solar cells that are being researched now that could takes things to a whole new level.

Solar-Collecting Paint is an exciting future possibility.

Imagine the paint on your house or a building acting as a solar panel? Or how about your car? Chemistry professor Richard L. Brutchey from University of Southern California and researcher David H. Webber successfully developed solar collecting paint by using solar-collecting nanocrystals. At only 4 nanometers in size, nanocrystals can float in a liquid solution. You could potentially fit 250 billion nanocrystals on the head of a pin, they’re THAT small. Brutchey and Webber were able to find an organic molecule that would keep the nanocrystals conductive without sticking to each other.

So why isn’t this available in the market yet? Well those nanocrystals were built with cadmium, which is a toxic metal. Researchers have been busy trying to find alternative materials and there are some really promising leads.

Quantum dot solar cells

Quantum dot solar cells are one area to look at. Quantum dots are semiconducting particles that behave differently due to their size and the effects of quantum mechanics, like I mentioned earlier. They have energy similarities to atoms, which is why they’re sometimes referred to as “artificial atoms.” In June 2020 researchers at the Los Alamos National Laboratory were able to create cadmium-free Quantum Dot solar cells. Their zinc-doped variant has a high defect tolerance and is toxic-element-free.

This year researchers at the University of Queensland were even able to break a new world efficiency record of 16.6% for a quantum dot solar cell made from a halide Perovskite. That’s a 25% improvement in relative efficiency compared to the last record holder from 2017, so there’s fast progress being made. But the big challenge is around commercialization of the breakthrough, so the university is working on a large scale printing process in addition to continuing to improve the efficiency.

Perovskite solar paint

In 2014, researchers at the University of Sheffield were able to develop a spray on solar cell using Perovskite which is a class of man-made compounds that share the same crystalline structure as the calcium titanium oxide mineral with the same name.2,3 It happens to be one of the most promising solar technologies in recent years because it has a broad absorption spectrum. It consists of a 300 nanometer thin film with a crystal structure that aids solar absorption and can operate efficiently during cloudy days as well. Scientific Director at Saule Technologies, Dr. Konrad Wojciechowski, says that this could be printed using an inkjet printer.4

Swedish firm Skanska tested it on a building in 2019 and is expected to start producing it in 2021 with the expected cost to be $58 per meter and an efficiency around 10%.

The reason why all of these examples are so exciting is that a paintable solar cell opens up the floodgates for where you can apply solar power. Painting the walls of a building, not just the roof, or as I mentioned earlier, your car. It should also help to reduce the costs of manufacturing solar technologies, which will make it more accessible. It’s potentially a huge win/win.

Energy Storage

The second category I wanted to look at for this video is nanotechnology being applied to energy storage. In a previous video I’ve walked through graphene and carbon nanotubes and how they’re impacting energy storage today. Specifically, in my supercapacitor video I talked about how companies like NAWA Technologies and Skeleton are building out graphene-based supercapacitors today. Skeleton’s products can be found helping to power major tram-systems in big European hubs like Warsaw and Mannheim.5

As a quick refresher, batteries and supercapacitors share some similarities in how they work. In a battery there’s a positive and negative side, which are called the cathode and anode. Those two sides are submerged in a liquid electrolyte and are separated by a micro perforated separator, which only allows ions to pass through. When the battery charges and discharges, the ions flow back and forth between the cathode and anode. But capacitors are different, they don’t rely on chemical play in order to function. Instead, they store potential energy electrostatically. Capacitors use a dielectric, or insulator, between their plates to separate the collection of positive and negative charges building on each plate. It’s this separation that allows the device to store energy and quickly release it6. It’s basically capturing static electricity.

In one recent advancement in batteries from July 2020, scientists from Clemson Nanomaterials Institute were able to achieve high rate capability, fast diffusion, high capacity, and a long cycle life thanks to sandwiching silicone nanoparticles with carbon nanotubes called bucky papers.7 The cycle life for lithium batteries with silicon based anodes is less than 100, but thanks to the new sandwiched silicon electrode structure they were able achieve 500 cycles and deliver three times more capacity than graphite. Silicone happens to have ten times higher capacity than graphite, but it expands by about 300 percent in volume as it absorbs ions. The end result is an anode that breaks apart. This nanostructure counters this factor and would help us replace graphite with silicone, so that our batteries can become safer and lighter.

But I’ve saved the craziest research I’ve seen in a while for last… Nanotechnology could potentially turn bricks into batteries. …well, more like supercapacitors, but that doesn’t have the same alliteration. Washington University’s Institute of Materials Science & Engineering took work from their microsupercapacitor research using Fe2O3 (iron oxide – or rust) as a conducting polymer, also known as rust-assisted vapor-phase polymerization. Rolls right off the tongue. I’m not going to get bogged down into the technical details, partially because of my broken brain, but what sets this process apart is that the nanostructures formed by this process are self-assembled. Other processes like this might take several steps and treatments, which makes this process unique.

So I can hear you asking how does this possibility relate to bricks? That red pigment in your classic brick is … you probably guessed it … Fe2O3 (iron oxide – or rust). By applying their polymer process to a standard red brick, you end up with a capacitor.8 Julio D’Arcy, assistant professor of chemistry, who worked on this research, described it:

“In this work, we have developed a coating of the conducting polymer PEDOT, which is comprised of nanofibers that penetrate the inner porous network of a brick; a polymer coating remains trapped in a brick and serves as an ion sponge that stores and conducts electricity.” -Julio D’Arcy, Assistant Professor9

This process leaves a blue PEDOT coating on one side of the brick, so that could be easily hidden on one side of the brick wall. They estimate that it would take about 50 bricks to power an emergency lighting system for 5 hours, so this clearly isn’t going to power your entire house. But then again, a building is made up of thousands of bricks, so there’s a potential for a building’s brick walls to act as a massive supercapacitor to absorb solar panel overproduction, or to cover peak energy use to smooth out demand, and pair with battery storage in a hybrid setup.

We’re already seeing some of nanotechnologies benefits in the world around us today, but the research and advancements we’re seeing in the lab, like these, are what to look forward to for the future. Nanotech may have been an overused and blanket term that’s lost a little bit of it’s meaning to most of us, but there’s real progress being made.


  1. Nano.gov, “Size of the Nanoscale” ↩︎
  2. Energysage, “Perovskite solar cells: the future of solar?” ↩︎
  3. Wikipedia, “Perovskite solar cell” ↩︎
  4. Energy & Environmental Science, “Towards the commercialization of colloidal quantum dot solar cells: perspectives on device structures and manufacturing” ↩︎
  5. Railway Technology, “Skeleton Technologies to provide ultracapacitor for Warsaw tram system” ↩︎
  6. Green Techee, “How does an ultracap work?” ↩︎
  7. New Atlas, “Silicon ‘sandwiches’ make for lightweight, high-capacity batteries” ↩︎
  8. Nature Communications, 11, “Energy storing bricks for stationary PEDOT supercapacitors” ↩︎
  9. Washington University in St. Louis – The Source, “Storing energy in red bricks” ↩︎

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