Coronavirus treatment options and the impact on public policy

"Remdesivir works by gumming up an enzyme that some viruses, including SARS-CoV-2, use to replicate. In February, researchers showed2 that the drug reduces viral infection in human cells grown in a laboratory. "

If this is what I think it is the enzyme snips the virus apart. This allows each piece to replicate.

printer said:

"Remdesivir works by gumming up an enzyme that some viruses, including SARS-CoV-2, use to replicate. In February, researchers showed2 that the drug reduces viral infection in human cells grown in a laboratory. "

If this is what I think it is the enzyme snips the virus apart. This allows each piece to replicate.

Click to expand...

Here is an easy way to get an overview of how it inhibits viral replication.
[COVID-19 and Remdesivir animation] How Coronavirus replicates and How Remdesivir works?

We found and tested 47 old drugs that might treat the coronavirus: Results show promising leads and a whole new way to fight COVID-19
April 30, 2020 2.26pm EDT

The more researchers know about how the coronavirus attaches, invades and hijacks human cells, the more effective the search for drugs to fight it. That was the idea my colleagues and I hoped to be true when we began building a map of the coronavirus two months ago. The map shows all of the coronavirus proteins and all of the proteins found in the human body that those viral proteins could interact with.

In theory, any intersection on the map between viral and human proteins is a place where drugs could fight the coronavirus. But instead of trying to develop new drugs to work on these points of interaction, we turned to the more than 2,000 unique drugs already approved by the FDA for human use. We believed that somewhere on this long list would be a few drugs or compounds that interact with the very same human proteins as the coronavirus.

We were right.

Our multidisciplinary team of researchers at the University of California, San Francisco, called the QCRG, identified 69 existing drugs and compounds with potential to treat COVID-19. A month ago, we began shipping boxes of these drugs off to Institut Pasteur in Paris and Mount Sinai in New York to see if they do in fact fight the coronavirus.

In the last four weeks, we have tested 47 of these drugs and compounds in the lab against live coronavirus. I’m happy to report we’ve identified some strong treatment leads and identified two separate mechanisms for how these drugs affect SARS-CoV-2 infection. Our findings were published on April 30 in the journal Nature.
more...

Fauci Says It's 'Doable' To Have Millions Of Doses Of COVID-19 Vaccine By January

There's a chance that hundreds of millions of doses of a potential COVID-19 vaccine could be available by early next year, Dr. Anthony Fauci, a key member of the White House coronavirus task force, said Thursday, even though the federal government has not approved a vaccine against the virus.

In an appearance on NBC's Today Show, Fauci was asked whether he thought it was "in the realm of possibility" to have a potential vaccine ready for wide distribution by January.

"I do," Fauci replied. "I mean, I'm obviously part of the team that's involved in that."

Fauci, who heads the National Institute of Allergy and Infectious Diseases, noted that the ideal plan for a potential vaccine is to ensure it is safe and effective — and can be rapidly scaled up for distribution.

Of course, the Food and Drug Administration has not approved a vaccine for the coronavirus. Noting that vaccine trials are still in the early phase, Fauci added that to accelerate production, the companies making the medicine would need to do so "at risk."

"In other words, you don't wait until you get an answer before you start manufacturing. You at risk — proactively — start making it, assuming it's going to work," Fauci said. "And if it does, then you can scale up and hopefully get to that timeline."

"I think that is doable if things fall in the right place," Fauci said.

Fauci was responding to a question about media reports that the Trump administration is launching a project dubbed Operation Warp Speed, to speed up delivery of a vaccine against COVID-19. The deadly disease has been diagnosed in more than a million people in the U.S.

The White House plan aims to bring together pharmaceutical companies, government agencies and the military with the goal of substantially shrinking the development time for a vaccine.

Bloomberg News, which first reported the existence of the plan to accelerate vaccine delivery, says the government's goal is to have as many as 300 million vaccine doses by early 2021.

As NPR science correspondent Joe Palca has reported, advances in science have revolutionized the speed at which vaccines can be developed.

"In the past it used to take 5-10 years to make a vaccine, and now people are talking about a year or 18 months. So it's really going faster than expected," Palca reported on NPR's Morning Edition this month.

He added that in addition to a vaccine that is safe for people, there are other factors to consider.

"You want one that generates a strong and lasting immune response. You need to be able to manufacture it. Sometimes you come up with a brilliant idea of how to package the virus and you just can't make it at a scale that would be useful. You want to have a vaccine that doesn't require special handling," Palca reports.

During the NBC interview, Fauci was asked whether he is nervous that stay-at-home orders are beginning to lift in many states, including Alabama, Texas, Arizona and Florida.

White House social distancing guidelines are set to expire at the end of April.

Fauci declined to give detailed assessments on individual states, but he pointed to White House guidelines for reopening state and local economies, which call for a "downward trajectory" of documented COVID-19 cases over a 14-day period.

Fauci said he expects to see an uptick in coronavirus cases when towns and states reopen for business.

"When you pull back, there will be cases," Fauci said. "And what we need to do is make sure they have in place the capability of identifying, isolating and contact-tracing individuals."

While he said he was "cautiously optimistic," Fauci also said governments must have "the core principles of the guidelines" before reopening.

"You can't just leap over things and get into a situation where you're really tempting a rebound. That's the thing I get concerned about," Fauci said. "I hope they don't do that."

Opinion
Could ‘Innate Immunology’ Save Us From the Coronavirus?
Researchers are testing whether decades-old vaccines for polio and tuberculosis could protect against infection.

By Melinda Wenner Moyer
Ms. Moyer is a science and health writer.

As the world waits for a coronavirus vaccine, tens of thousands of people could die. But some scientists believe a vaccine might already exist.

Surprising new research in a niche area of immunology suggests that certain live vaccines that have been around for decades could, possibly, protect against the coronavirus. The theory is that these vaccines could make people less likely to experience serious symptoms — or even any symptoms — if they catch it.

At more than 25 universities and clinical centers around the world, researchers have begun clinical trials, primarily in health care workers, to test whether a live tuberculosis vaccine that has been in use for 99 years called the bacillus Calmette-Guérin, or B.C.G., vaccine, could reduce the risks associated with the coronavirus.

Another small but esteemed group of scientists is raising money to test the potential protective effects of a 60-year-old live polio vaccine called O.P.V.

It’s counterintuitive to think that old vaccines created to fight very different pathogens could defend against the coronavirus. The idea is controversial in part because it challenges the dogma about how vaccines work.

But scientists’ understanding of an arm of immunology known as innate immunity has shifted in recent years. A growing body of research suggests that live vaccines, which are made from living but attenuated pathogens (as opposed to inactivated vaccines, which use dead pathogens) provide broad protection against infections in ways that no one anticipated.

“We can’t be certain as to what the outcome will be, but I suspect it’ll have an effect” on the coronavirus, said Jeffrey Cirillo, a microbiologist and immunologist at Texas A&M University who is leading one of the B.C.G. trials. “Question is, how big will it be?”

Scientists stress that these vaccines will not be a panacea. They might make symptoms milder, but they probably won’t eliminate them. And the protection, if it occurs, would most likely last only a few years.

Still, “these could be a first step,” said Dr. Mihai Netea, an immunologist at Radboud University in the Netherlands who is leading another one of the trials. “They can be the bridge until you have the time to develop a specific vaccine.”

The first evidence to suggest that live vaccines could be broadly protective trickled in nearly a century ago, but no one knew what to make of it. In 1927, soon after B.C.G. was rolled out, Carl Naslund of the Swedish Tuberculosis Society observed that children vaccinated with the live tuberculosis vaccine were three times less likely to die of any cause compared with kids who weren’t.

“One is tempted to explain this very low mortality among vaccinated children by the idea that B.C.G. vaccine provokes a nonspecific immunity,” he wrote in 1932.

Then, in clinical trials conducted in the 1940s and ’50s in the United States and Britain, researchers found that B.C.G. reduced nonaccidental deaths from causes other than tuberculosis by an average of 25 percent.

Also in the 1950s, Russian researchers, including Marina Voroshilova of the Academy of Medical Science in Moscow, noticed that people who had been given the live polio vaccine, compared with people who hadn’t, were far less likely to fall ill with the seasonal flu and other respiratory infections. She and other scientists undertook a clinical trial involving 320,000 Russians to more carefully test these mysterious effects.

They found that among individuals who had received the live polio vaccine, “the incidence of seasonal influenza was reduced by 75 percent,” said Konstantin Chumakov, Voroshilova’s son, who is now an associate director for research in the U.S. Food and Drug Administration’s Office of Vaccines Research and Review.

Recent studies have produced similar findings. In a 2016 review of 68 papers commissioned by the World Health Organization, a team of researchers concluded that B.C.G., along with other live vaccines, “reduce overall mortality by more than would be expected through their effects on the diseases they prevent.”
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Gilead gets emergency FDA authorization for remdesivir to treat coronavirus, Trump says
PUBLISHED FRI, MAY 1 20203:46 PM EDTUPDATED AN HOUR AGO

POINTS

• The Food and Drug Administration has granted emergency use authorization for Gilead’s remdesivir drug to treat the coronavirus, President Donald Trump announced Friday.
• Trump made the announcement in the Oval Office alongside Gilead CEO Daniel O’Day.
• The EUA means that remdesivir has not undergone the same level of review as an FDA-approved treatment, according to a fact sheet from the agency about the drug.

The Food and Drug Administration has granted emergency use authorization for Gilead Sciences’ remdesivir drug to treat Covid-19, the disease caused by the coronavirus, President Donald Trump announced Friday.

Trump made the announcement in the Oval Office alongside Gilead CEO Daniel O’Day.

“We want to thank the collaborators that brought remdesivir to this point and many of our people that have been part of this, in fact, the caregivers,” O’Day told reporters. Gilead is donating 1.5 million vials of remdesivir.

Gilead shares pared losses on the news, and closed Friday down 4.8% at $79.95. However, the stock was up nearly 2% in extended trading. It has a market value of about $101 billion and has gained 21% since the start of the year.

The EUA means that remdesivir has not undergone the same level of review as an FDA-approved treatment, according to a fact sheet from the agency on the drug. However, doctors will be allowed to use the drug on patients hospitalized with the disease even though the drug has not been formally approved by the agency.

The intravenous drug has helped shorten the recovery time of some hospitalized Covid-19 patients, new clinical trial data suggests. Without other proven treatments, health-care workers will likely be considering its use.
more...

OFF WITH A SHOT —
The Ars COVID-19 vaccine primer: 100-plus in the works, 8 in clinical trials
Here's where we are and what may lie ahead for a vaccine against COVID-19.

The clearest way out of the COVID-19 crisis is to develop a safe, effective vaccine—and scientists have wasted no time in getting started.

They have at least 102 vaccine candidates in development worldwide. Eight of those have already entered early clinical trials in people. At least two have protected a small number of monkeys from infection with the novel coronavirus, SARS-CoV-2, that causes COVID-19.

Some optimistic vaccine developers say that, if all goes perfectly, we could see large-scale production and limited deployment of vaccines as early as this fall. If true, it would be an extraordinary achievement. Less than four months ago, SARS-CoV-2 was an unnamed, never-before-seen virus that abruptly emerged in the central Chinese city of Wuhan. Researchers there quickly identified it and, by late January, had deciphered and shared its genetic code, allowing researchers around the world to get to work on defeating it. By late February, researchers on multiple continents were working up clinical trials for vaccine candidates. By mid-March, two of them began, and volunteers began receiving the first jabs of candidate vaccines against COVID-19.

It’s a record-setting feat. But, it’s unclear if researchers will be able to maintain this break-neck pace.

Generally, vaccines must go through three progressively more stringent human trial phases before they are considered safe and effective. The phases assess the candidates’ safety profile, the strength of the immune responses they trigger, and how good they are at actually protecting people from infection and disease.

Most vaccine candidates don’t make it. By some estimates, more than 90 percent fail. And, though a pandemic-propelled timeline could conceivably deliver a vaccine in as little as 18 months, most vaccines take years—often more than 10 years, in fact—to go from preclinical vetting to a syringe in a doctor’s office.

Abridging that timeline can up the risk of failure. For instance, vaccine candidates usually enter the three phases of clinical trials only after being well tested in lab animals that can model the human disease. But, with such a new virus, there is no established animal model for COVID-19. And amid a devastating pandemic, there’s not enough time to thoroughly develop one. Some researchers are now doing that ground-level animal work in parallel with human trials—such as the small monkey trials mentioned above.

Researchers already have reason to be a little anxious about the safety of any COVID-19 vaccine. When they tried in the past to make vaccines against some of SARS-CoV-2’s coronavirus relatives, they found a small number of instances when candidate vaccines seemed to make infections worse. That is, these candidate vaccines seemed to prompt berserk immune responses that caused lung damage in monkeys and liver damage in ferrets. Researchers still don’t fully understand the problem and don’t know if it could happen in humans, let alone if it will show up with the new candidate vaccines against SARS-CoV-2.

But we may soon know the answers. As the pandemic tops the grim milestone of three million cases worldwide and well over 200,000 deaths, researchers are relentlessly moving forward with vaccine development. Here's where the scientific community currently stands in its frenetic effort.
more...

New report says coronavirus pandemic could last for two years – and may not subside until 70% of the population has immunity

As coronavirus restrictions around the world are being lifted, a new report warns the pandemic that has already killed more than 230,000 people likely won't be contained for two years. The modeling study from the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota also says that about 70% of people need to be immune in order to bring the virus to a halt.


For the study, experts looked at eight major influenza pandemics dating back to the 1700s, as well as data about the new coronavirus, to help forecast how COVID-19 may spread over the coming months and years. Out of the eight past flu pandemics, scientists said seven had a second substantial peak about six months after the first one. Additionally, some had "smaller waves of cases over the course of 2 years" after the initial outbreak.

A key factor in their prediction for the current pandemic revolves around herd immunity, which refers to the community-wide resistance to the spread of a contagious disease that results when a high percentage of people are immune to it, either through vaccination or prior exposure.

"The length of the pandemic will likely be 18 to 24 months, as herd immunity gradually develops in the human population," the report says. "Given the transmissibility of SARS-CoV-2" — the virus that causes COVID-19 — "60% to 70% of the population may need to be immune to reach a critical threshold of herd immunity to halt the pandemic."

It will take time to reach that point, since data from blood tests show only a small fraction of the overall population has been infected so far, and a possible vaccine is still months if not a year or more away. It is not yet clear whether people who've recovered from the infection will be immune or how long such protection would last.

The report lays out several possible scenarios, including one in which a larger wave of illnesses may happen in the fall or winter of 2020 and then subsequent smaller waves in 2021. The researchers say this model — similar to the pattern seen in the devastating 1918 Spanish flu pandemic — would "require the reinstitution of mitigation measures in the fall in an attempt to drive down spread of infection and prevent healthcare systems from being overwhelmed."

Two other scenarios in the report involve either recurring peaks and valleys of outbreaks, or smaller waves of illness over the next two years.
more...

The novel coronavirus is a master of disguise: Here's how it works

The novel coronavirus uses a number of tools to infect our cells and copy itself. What we've learned about the structure and behavior of the SARS and MERS coronaviruses can help in the fight against covid-19. Read more: https://wapo.st/2xqPQTZ.

COVID-19: The CIDRAP Viewpoint
Introduction
When severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)—the virus that causes COVID-19—first
emerged in Wuhan, China, in December 2019, even the most experienced international public health experts did
not anticipate that it would rapidly spread to create the worst global public health crisis in over 100 years. By
January 2020, a few public health officials began sounding the alarm, but it wasn’t until March 11, 2020, that the
World Health Organization declared a global pandemic.
The virus caught the global community off guard, and its future course is still highly unpredictable; there is
no crystal ball to tell us what the future holds and what the “end game” for controlling this pandemic will be.
The epidemiology of other serious coronaviruses (SARS-CoV-1, the virus that causes severe acute respiratory
syndrome [SARS] and Middle East respiratory syndrome coronavirus [MERS-CoV]) is substantially different
from that of SARS-CoV-2; therefore, these pathogens do not provide useful models for predicting what to expect
with this pandemic.
Alternatively, our best comparative model is pandemic influenza. Since the early 1700s, at least eight global
influenza pandemics have occurred, and four of these occurred since 1900—in 1918-19, 1957, 1968, and 2009-
10. We can potentially learn from past influenza pandemics as we attempt to determine a vision for the future
of the COVID-19 pandemic. Identifying key similarities and differences in the epidemiology of COVID-19 and
pandemic influenza can help envisioning several possible scenarios for the course of the COVID-19 pandemic.
The primary focus of these scenarios is on the temperate Northern Hemisphere, but similar patterns could
occur in the Global South, as well. The lack of robust healthcare infrastructure (including a dearth of adequate
personal protective equipment) and comorbidities such as other infections (eg, HIV, TB, malaria), malnutrition,
Part 1: The Future of the COVID-19 Pandemic: Lessons from
Pandemic Influenza
3
and chronic respiratory disease in certain areas of the Global South could result in the pandemic being even more
severe in those areas, as was noted during the 1918-19 pandemic (Murray 2006).

Lot's of info on remdesivir in this interview.
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Gilead's moving quickly with FDA for approval of coronavirus drug remdesivir: CEO

Gilead Sciences, the maker of the experimental coronavirus drug remdesivir, is giving investors more details. The company said it plans to expand manufacturing of the drug. It spent $50 million on remdesivir research and develeopment in the first quarter, and it's focused on making the drug accessible and affordable. Gilead Sciences CEO Daniel O'Day joins "Squawk Box" and CNBC's Meg Tirrell to discuss.

Gilead Sciences is working to make experimental antiviral drug remdesivir accessible and affordable to coronavirus patients, but the company will eventually need to transition to a more “sustainable model,” CEO Daniel O’Day said Friday.

“We understand our responsibility both to patients and also to shareholders and we’ll be balancing that,” he said during an interview with CNBC’s “Squawk Box.”

Gilead has said it is prepared to donate 1.5 million doses of its drug to patients hospitalized with Covid-19. However, O’Day said the research and manufacturing of the drug require investment.

Gilead spent $50 million on the research and development of remdesivir during the first quarter, the company disclosed in its earnings report Thursday. The company said it will spend as much as $1 billion for the year.

“There is no playbook for this situation that we’re in today,” he said. “This is the time for us all as an industry, especially Gilead, to do the right thing.”

Gilead shares, which have a market value just under $100 billion, are trading down more than 5% Friday. The stock is up nearly 22% so far this year.

On Wednesday, Gilead released preliminary results from its clinical trial on remdesivir, showing at least 50% of the Covid-19 patients treated with a five-day dosage of the drug improved. The clinical trial involved 397 patients with severe cases of Covid-19. The severe study is “single-arm,” meaning it did not evaluate the drug against a control group of patients who didn’t receive the drug.

The National Institute of Allergy and Infectious Diseases also released results from its own study Wednesday. It showed Covid-19 patients who took remdesivir usually recovered after 11 days, four days faster than those who didn’t take the drug.

There must be something to it after all, these morons are going for the HCQ and Clorox! Seems the don't like no big science either and this is too scieney for them, too many liberals involved. Wait until Donald jumps on board with both feet, I don't understand why he hasn't been touting it, maybe fox hasn't been, so he hasn't. I hope he doesn't fuck things up, but he probably will.
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Coronavirus gets a promising drug. MAGA world isn’t buying it.
On the heels of positive early signs for remdesivir, several prominent Trump boosters are downplaying the results and continuing to promote hydroxychloroquine.

Over three weeks ago, hydroxychloroquine was all the rage in MAGA world, despite flawed and scattered evidence about whether the drug could help cure coronavirus. Now there is another drug, remdesivir, with positive early scientific data.

Much of MAGA world wants little to do with it.

At first, it may seem like a head-scratching response. President Donald Trump’s base has been quick to trumpet any potential solutions to the coronavirus pandemic — especially those Trump himself promotes — regardless of the red flags from medical experts. But with remdesivir, it’s the Trump-boosting pundits who are raising the red flags, even as the president expresses optimism.

Indeed, the same segment of the right that claimed scientists and the media were deliberately downplaying hydroxychloroquine in order to hurt Trump’s standing are now the ones downplaying remdesivir. On Fox News, Laura Ingraham suggested that remdesivir, as a newer drug being produced by the pharmaceutical company Gilead Sciences, could be unsafe and expensive. Those who initially helped raise the profile of hydroxychloroquine raised doubts about the remdesivir studies.

The unexpected reaction appears to stem from the differences in how the two drugs came into the public spotlight. Hydroxychloroquine bubbled up through the MAGA grassroots — little-known investors promoted it online, got on Fox News and suddenly the president was talking about it from the White House. Remdesivir’s progress came through a government-funded trial that had the blessing of Dr. Anthony Fauci, the bête noire of Trump hardliners who blame the government’s top infectious disease expert for undermining the president and causing unnecessary economic damage with his social-distancing guidelines.

Remdesivir’s connection to a pharmaceutical company also taps into suspicions on the right that corporate executives are trying to rake in huge profits from the coronavirus. Hydroxychloroquine, on the other hand, is already widely available in generic form.

These factors were likely enough to turn off people who had been using hydroxychloroquine as a political rallying cry, said David Rapp, a psychology professor at Northwestern University who studies how misinformation shapes beliefs and memory.
more...

FDA approves remdesivir to treat some Covid-19 patients

The experimental drug remdesivir has been approved to treat hospitalized patients with severe Covid-19, the US Food and Drug Administration said.
The FDA issued an emergency-use authorization, saying the benefits of the drug outweigh its risks in patients. An emergency-use authorization is a lower regulatory bar than full FDA approval. CNN's Sara Sidner reports.

First drug known to work against SARS-CoV-2 imaged in action
Structural details of how remdesivir keeps the virus from making copies of itself.
JOHN TIMMER - Yesterday at undefined


Enlarge / The RNA being copied is in dark blue; the copy is in turquoise; the enzyme is in pale green; and the drug is in pink.

Just this week, we had the first promising report of a drug that appears to improve the recovery time of patients suffering from COVID-19. Hot on the heels of that announcement, a scientific journal has released a paper that describes how the drug interferes with the virus. While there's no real surprises in what has been revealed, it provides key details of how SARS-CoV-2 can be blocked.

Copying machine
Targeting a virus with a drug is a challenge. Viruses make their living by using their host's proteins to do most of the work of making new viruses. That means a drug has to target some of the few proteins encoded by the virus while not interfering with any of the far more prevalent host cell proteins. In the case of the coronavirus, biologists have identified a number of distinct features of the virus that may be targeted without an obvious risk of causing severe side effects.

FURTHER READING
COVID-19: The biology of an effective therapy
Remdesivir, which saw a large clinical trial produce promising results, is a drug that's designed to target one of these virus-specific vulnerabilities. The coronavirus genome is encoded using the chemical RNA, as opposed to the DNA used for our genome. In fact, there's nothing about our cells that requires them to make an RNA copy of an RNA molecule. As a result, the coronavirus genome encodes proteins that do this RNA-to-RNA copying, called an RNA-dependent RNA polymerase. Remdesivir was designed to look like one of the building blocks of RNA in the hope that it would bind to an RNA virus' polymerase and inhibit it.

That said, this drug was designed with the intention of inhibiting the polymerase of a different virus (Ebola), so it wasn't guaranteed to work against coronavirus. And our cells need to make RNA copies of DNA, a process that's similar enough that remdesivir could interfere with that, too.

Still, tests in cells had been promising enough to drive testing in humans. While that testing was starting, a group of Chinese scientists decided to look into how remdesivir actually works. To do so, they decided to figure out how the drug interacted with the coronavirus RNA polymerase at the atomic level. And that requires a technique to determine where all the atoms in the protein and drug are.

A few decades ago, figuring out atomic-level details of proteins would have required many months of laboriously trying to get the drug and protein to form neat, orderly crystals. But we've since developed a combination of hardware and algorithms that now allow us to take what are essentially electron microscope images of individual proteins and combine them with enough precision to figure out where all the atoms are. The technique, called cryo electron microscopy, has been so revolutionary that it earned the people who developed it a Nobel Prize.

FURTHER READING
Algorithm designer among those honored with the Chemistry Nobel
These scientists also benefited from earlier work on other coronaviruses, which had identified three different proteins that were critical for copying the virus' genome. One of these is the enzyme that actually strings together individual units called "bases" to form a new RNA molecule. The other proteins in question simply help it clamp down on and move along the RNA it makes a copy of. So the researchers produced these three proteins, put in an RNA template and a partial copy, and then added remdesivir.

In the atoms
Well, they didn't technically add remdesivir. Bases are added to RNA in a form with three phosphates attached. That form is very negatively charged, and it won't make it across membranes very easily. Instead, the drug is provided in a form with minimal charge, which can transit across cell membranes. Once inside the cell, the cell's own enzymes convert it into the charged form, which then gets used by the RNA-copying enzyme. Since they weren't working in cells, the researchers had to do this conversion themselves. It's a bit of an aside, but it illustrates some of the challenges that the people doing drug development face.

In any case, the imaging technique requires taking thousands of electron micrographs of individual protein-RNA-drug complexes, all of them oriented randomly. While none of these is, on its own, enough to figure out where the atoms are, computer algorithms are able to combine all of these images and figure out what the underlying structure that's compatible with all of these different images.

In the end, after over 80,000 images were combined, the resolution of the structure they determined had a precision of about 2.5 angstroms (10-10 meters). For comparison, a carbon atom in these same molecules has a width of about 1.5 angstroms. But given the fact that many configurations consistent with this resolution make no sense—they place two carbon atoms on top of each other or something similar—the picture is quite detailed.

One thing they discovered is that the proteins involved have zinc atoms incorporated into their structure. This won't surprise any biochemists, as zinc-containing proteins are common. But there's been a steady flow of fringe treatments for the disease—including some involving chloroquine derivatives—in which zinc was a key component. We'll have to see whether that changes now that it's clear that zinc is needed to make copies of the virus (assuming that fact registers at all with the people prone to promoting fringe therapies).

The structure confirms that remdesivir doesn't just stick to the enzyme and block it. Instead, the drug is chemically incorporated into the growing chain of RNA. Once there, however, it doesn't have the right chemistry for another base to be added afterwards. As a result, the RNA can't grow any further. Copying gets terminated, and the resulting genome is defective. This is the same sort of drug mechanism that was behind some of the earliest drugs against HIV, like AZT.

Why doesn't this block the virus entirely? Presumably because there's simply a lot more of the normal equivalent of RNA building blocks in the cell, and it's difficult to get the drug up to concentrations where it consistently damages all the viral copies being made. An added limitation is that, once the drug blocks the copying of one molecule, it's essentially inactivated, since it stays chemically linked to that molecule.

The researchers note that there are other, similar drugs that bind to the coronavirus RNA polymerase even more effectively. So there's a chance we can get the structure of a few of those and figure out whether there are rules for what sort of chemicals are especially good at sticking to the coronavirus enzyme.

Gilead has a complex manufacturing supply chain: Former FDA chief Dr. Scott Gottlieb

Dr. Scott Gottlieb, member of the boards of Pfizer and biotech company Illumina and former FDA commissioner, joins "Squawk Box" to respond to Gilead CEO Daniel O'Day's comments to CNBC and to discuss the latest in the development of a Covid-19 vaccine.

Gilead Sciences is working to make experimental antiviral drug remdesivir accessible and affordable to coronavirus patients, but the company will eventually need to transition to a more “sustainable model,” CEO Daniel O’Day said Friday.

Fighting coronavirus with blood | COVID-19 Special

So far there are no specific medications or vaccines for COVID-19. But doctors suggest that blood plasma of former COVID-19 patients could help to cure the disease, as it contains antibodies. That’s the idea. But how could it work?

Popular heartburn medicine being studied as treatment for coronavirus
Could an old heartburn drug emerge as a treatment for COVID-19?

Over the past few weeks researchers have been discreetly studying a new potential treatment for COVID-19 -- and it might not be what you expect.

The treatment in question is called famotidine, and it's the active ingredient in Pepcid, an over-the-counter medication commonly used to alleviate heartburn.

Since March 13, researchers at Northwell Health, a network of hospitals in New York, have been enrolling patients hospitalized with COVID-19 into their study of famotidine, which is being delivered through an IV in megadoses nine times greater than the typical over-the-counter dose. The drug is being given in combination with the much-touted antimalarial hydroxychloroquine.

Researchers said some data on safety will be available "in a few weeks," but did not say when data will be available showing whether the drug combination is effective.

MORE: ABC News – Breaking News, Latest News, Headlines & Videos
Dr. Kevin Tracey, CEO and president of the Feinsteins Institute for Medical Research at Northwell Health, says the study was being conducted under the radar to avoid media attention as well as a potential depletion of national supply, limiting Northwell's access to the drug.

More than 180 patients have enrolled in the Northwell study so far. They've been given either a two-drug combination of hydroxychloroquine and famotidine, or hydroxychloroquine alone. According to Tracey, hydroxychloroquine was added into the mix because of the drug's promise back in mid-March -- before data emerged about its potential risks.

Tracey said the idea to try famotidine came from a friend and colleague, Dr. Michael Callahan, who had recently visited China and was working with Chinese physicians on a still-unpublished study reportedly showing that the drug benefited patients with COVID-19.

The merit of trying famotidine was supported by additional research, part of a private-public partnership with the federal government, that used the genetic makeup of the virus to pinpoint potentially promising drugs, Tracey said.

The hope is that famotidine will act as a decoy for the virus, so that while the virus is preoccupied with famotidine, it is unable to reproduce itself and spread throughout the body.

MORE: A reality check on antibody testing: How do we race forward thoughtfully?
Dr. Stuart Ray, professor of medicine in infectious diseases and vice chair of medicine for data integrity and analytics at Johns Hopkins, said he was surprised to hear that researchers at Northwell are studying famotidine in people with COVID-19, and that he is skeptical about preliminary data from China because it has not been vetted in the typical review process.

However, he said he is glad there is some scientific rationale behind the drug. He adds that despite the megadoses, the drug is likely to be safe.

"I think this sort of off-label repurposing is sensible with drugs for which we have a long safety record," said Ray. "And we really need a win."
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DIY-HP-LED said:

Donate COVID-19 Plasma

If you have fully recovered from COVID-19, you may be able to help patients currently fighting the infection by donating your plasma.

www.fda.gov

Donate COVID-19 Plasma

If you have fully recovered from COVID-19, you may be able to help patients currently fighting the infection by donating your plasma. Because you fought the infection, your plasma now contains COVID-19 antibodies. These antibodies provided one way for your immune system to fight the virus when you were sick, so your plasma may be able to be used to help others fight off the disease.

Click to expand...

I don't think the plasma is supposed to be green.

New York Clinical Trial Tests Heartburn Remedy Against Coronavirus

Hospitals in New York have been quietly testing famotidine, the active ingredient in usual heartburn medication like Pepcid as a potential treatment for coronavirus. They predict it to be the most rapid list of possible treatments to date. The researchers at Northwell Health, a network of hospitals in the NYC area, have been delivering famotidine. They do it through an IV in doses nine times greater than the typical products in stores. In charge of the hospital system’s research is Dr Kevin Tracey, a former neurosurgeon. He is also the president of Feinstein Institutes for Medical Research at Northwell Health.

About the New York study being conducted, Tracey said: “If it does work, we’ll know in a few weeks”. He believes in keeping it under the carpet for the time being. It promotes unnecessary hype surrounding the drug, more so after President Trump’s cheeky enthusiasm of unproven hydroxychloroquine and chloroquine—the antimalarial drugs, it seemed rather appropriate.

According to the reports, hospitalized COVID-19 patients on famotidine exhibited a lower death rate of about 14% compared to the usual 27% for those not on the drug. Tracey warned against any potential benefits of heartburn drug since its too soon. And despite it likely being safe even, he urged the public not to try it at home. “You should not go to the drugstore and take a bunch of heartburn medicine,” he said.

Famotidine’s potential use for COVID-19 was first demonstrated in China. In the words of Science Magazine, Michael Callahan brought the news to Tracey in the United States. He is a globe-trotting infectious disease doctor and is based at Massachusetts General Hospital. He has prior experience of it from the 2003 outbreak of SARS, in Hong Kong. Callahan also checked in with Robert Malone, the CMO of Florida-based Alchem Laboratories.

It is a contract manufacturing organization. Malone is part of a classified project called DOMANE. It uses computer simulations, artificial intelligence, and other methods to rapidly identify U.S. FDA approved drugs that can be used against viruses.

During experimenting, he had his eyes on an enzyme that helped the pathogen replicate. They found the viral enzyme to be a papain-like protease. To see whether famotidine binds to the protein, Malon would ordinarily need the 3D structure of the enzyme. He appointed computational chemist Joshua Pottel, president of Montreal-based Molecular Forecaster. He helped to predict it from the 2003 SARS coronavirus, combined with the new coronavirus’ RNA sequence.

They compared the genes of the new and old to find crucial differences. They finally narrowed down to a few options including famotidine. Well, both the tantalizing Chinese data and the modelling pointed towards famotidine, Callahan finally contacted Tracey to run a double-blind arbitrary study.

Northwell channelized their funds to launch the effort after getting the FDA approval. With no extensive use of the injectable version, it took weeks just to get half of the needed famotidine in sterile vials. On 14 April, the U.S. Biomedical Advanced Research and Development Authority did a whopping $20.7 million contract for the trial. Fortunately, it was sufficient to fund Northwell’s costs.

Subsequently, David Tuveson, the director of the Cold Spring Harbor Laboratory Cancer Center spoke to Tracey. He then recommended famotidine to his sister. She had tested positive for COVID-19 and had developed a fever. Her lips had become dark blue from hypoxia and she was administered her first megadose of oral famotidine.

The day after, the fever broke and they observed a normal range of oxygen saturation. He says, “No amount of smart people at the National Institutes of Health, or Stanford or Harvard can outclass an average doctor in Wuhan” when asked about the experience tackling with COVID-19.

ANC said:

I don't think the plasma is supposed to be green.

Click to expand...

It depends on the planet you're from, or if you happen to be a crab.