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  • The Coming Virus Treatment Revolution

    Long before the COVID19 pandemic, the Trends editors forecast the crucial role messenger-RNA technology would play in prevention and treatment of viral infections as well as thwarting bioterrorism and fighting cancer.

    So, when the pandemic did arrive, we weren’t at all surprised that this new technology played an indispensable role in Operation WarpSpeed. And at the same time, we paid attention to new research in this area which paved the way for actual treatment of COVID.

    To understand the enormous potential of this new technology, consider the progress that’s been made outside the well-documented vaccine roll-out.

    In May 2020, when drug researchers were overwhelmed with developing and testing vaccines, a few experts began looking for cost-effective treatments that could help patients who had already contracted the virus. Specifically, a team of chemists at Pfizer dusted off some ideas the company had developed during the SARS outbreak in 2003.

    Nearly twenty years ago, one obvious line of attack involved inhibiting a well-understood element of the virus lifecycle by blocking an enzyme, called a protease, which orchestrates how the virus copies itself.

    The idea was to identify a chemical able to bind tightly enough to that protease so that it would stop the virus from replicating in the body, minimizing the chances that a patient would become seriously ill.

    As explained recently in MIT Technology Review, Pfizer quickly found that none of the thousands of proteins in the human body shared the same bit of molecular structure they planned to interfere with in the COVID19 virus. That meant they could aggressively inhibit that protein sequence without triggering dangerous side effects in the patient.

    From there, the process became a textbook example of scientific innovation. Pfizer sped the project forward by testing over 800 chemicals in parallel and then making huge batches of the most promising one.

    As a result, by December 2020, animal studies were underway on a drug named Paxlovid. Human trials began in March 2021. And by the fall of 2021, Pfizer was ready to declare success.

    That’s when the research monitoring board decided to stop the human study because covid-19 patients taking Paxlovid weren’t dying, while those given a placebo were. As a result, development of Paxlovid set a record for the fastest that any drug company ever moved from initial chemical synthesis to proof that the chemical safely treated a disease.

    Pfizer’s test in unvaccinated volunteers showed that the new pill cut the chances of a serious case of covid by 89%! And on this basis, the FDA authorized the pill’s sale on December 22, 2021, touting it as “a game changer.”

    However, this breakthrough is far more significant than it appears on the surface. Why? The most important thing about Paxlovid is that it is expected to work against all future variants of COVID as well as any conceivable coronavirus which may threaten humans.

    That’s because the targeted protein is “highly conserved.” That means that even as COVID19 and other coronaviruses mutate, the targeted molecule is unlikely to change. Therefore, it looks like Paxlovid will work just as well against any coronavirus nature may throw at us.

    In fact, laboratory tests run by Pfizer suggest Paxlovid will work against all coronaviruses, including ones still lurking in bat caves. If so, it means the company has hit on a potential defense against future outbreaks. Consequently, it has the potential to become a universal defense against coronaviruses which should be stockpiled against future pandemics.

    This is very important since a new vaccine for a new coronavirus will take months to develop, test, manufacture and deploy. Not having to wait, will save many lives and avoid huge economic damage.

    As of January 2022, the Biden administration had spent $10.6 billion to pre-purchase enough Paxlovid for 20 million patients. And those 20 million treatments are expected to be delivered by mid-2022. That’s too late to help with the Omicron surge in the United States, but those doses will be on-hand for any future coronavirus waves.

    If there is a negative to Paxlovid, it’s the narrow timeframe in which it must be taken to be fully effective. Specifically, it should be given within five days of the start of symptoms. An August 2021 study in the Annals of Emergency Medicine found that, on average, people have symptoms for five or six days before they turn up at a hospital. And even when patients are not that sick, there’s often a time lag while their infection is confirmed.

    For this reason, Pfizer has floated the idea of offering the drug to people while they wait for test results. And Pfizer is also running a study to see if the pills help people who’ve only been exposed to covid-19, as a sort of prophylactic treatment.

    What’s the bottom line? As with so many game-changing technologies made possible by the digital techno-economic revolution, RNA-based vaccines and antivirals are only in their infancy. Despite some problems with the first generation of vaccines, the mRNA genie is out of the bottle and it’s only a matter of time before it transforms the way society deals with viruses. That’s especially true, when it comes to treatment.

    Given this trend, we offer the following forecasts for your consideration.

    First, Paxlovid will prove to be a practical and cost-effective treatment for future coronavirus epidemics.

    At around $500 per person, Paxlovid is already a bargain. If Pfizer’s trial numbers stand up, doctors who give the drug to the patients at greatest risk could save about one person for every 100 they treat. That amounts to $50,000 per life. Better yet, medical economists say Paxlovid should be “cost negative” because the system will save money assuming it keeps enough people out of the hospital, because each hospitalization costs tens of thousands of dollars.

    More importantly, it could have largely prevented trillions of dollars in disruption caused by COVID19 lockdowns. And best of all, it’s bound to get cheaper as R&D is amortized, production becomes more efficient, and competition enters the market. That means the ROI will only get better.

    Second, stock-piling antiviral pills will provide an insurance policy against new COVID variants as well as new coronaviruses that are yet to be discovered.

    Covid-19 has surprised scientists again and again by mutating in ways that allow it to spread faster or evade immunity. This happens because the virus continually changes the “spike” molecules used to get into cells, and which are targeted by vaccines and antibodies.

    But these viruses can’t readily evolve ways of dodging Paxlovid because the targeted protease is very finely tuned for its job. And, importantly, even distantly related viruses have proteases that look very similar and can be thwarted by Paxlovid.

    Third, harnessing the power of digital technology will dramatically reduce the cost and delay in discovering new mRNA vaccines, anti-virals and cancer drugs.

    Already a scientist can give a computer an enzyme and say, ‘Design me a drug for this.’; it will then suggest perhaps 100 ideas. The next step is synthesizing those molecules and, there too, specialized computer applications can dramatically streamline the process by suggesting the simplest and most reliable synthesis pathway.

    Until recently, identifying the key properties of each candidate molecule - such as whether it is absorbed in the gut or broken down in the liver - required real-life tests on animals.

    But fortunately, so-called body-ona-chip technology can dramatically accelerate this process; and because it can use human tissues and organelles it can potentially enable the researchers to skip the earliest parts of human trials. The net result is a quicker less expensive process that will make such therapies commercially viable for a wider range of maladies.

    Fourth, by 2030, Paxlovid will be just one component of a standard cocktail given to treat viral infections preempting costly and deadly pandemics like the ones experienced in 1918 and 2020.

    The espoused goal of healthcare planners is to have an off-the-shelf solution ready the next time one of these major public health threats emerges. Top experts expect that one day soon, coronaviruses will be treated with a combination of antiviral drugs, similar to the “cocktails” already used to control HIV.

    These experts say, the more drugs in combination, the better. One reason is that multi-drug therapies protect better against mutant viruses; that’s because it’s harder for any virus to escape from two drugs than from one. More than a dozen new antivirals are already in development and the next generation could be even better than Paxlovid. And,

    Fifth, by 2035, healthcare providers will be able to cost-effectively deploy drugs that work against nearly any conceivable virus, even ones as different as Ebola and influenza.

    Researchers have identified some compounds that can do that by acting on the human body, rather than on parts of the virus. The idea is to exploit a whole new spectrum of ways to target viruses.

    The challenge is to find and commercialize them. In the past, there was little funding from government because the challenge seemed insurmountable. But new tools like body-on-a-chip makes success increasingly likely, while recent experience with COVID shows why it’s worthwhile to spend money getting ready for the next threat.

    To jump start this new era, the US government turned its attention back to antivirals in a big way, announcing in June 2021, that it would spend $3 billion on a major search for next-generation drugs. About half that money will be used to establish eight-to-10 new antiviral research centers that will target specific viruses

    Resource List
    1. MIT Technology Review. Antonio Regalado. February 4, 2022. How Pfizer made an effective anti-covid pill.

    2. MIT Technology Review. Antonio Regalado. February 5, 2021. The next act for messenger RNA could be bigger than covid vaccines.

    3. Trends. May 22, 2017. The Trends Editors. The RNA Miracle Unfolds.

    4. Trends. September 15, 2016. The Trends Editors. RNA Vaccines Destroy Cancer and Thwart Infectious Disease.