New Anti-viral (GC373) Could Soon Be Added To The Arsenal Of Effective Covid-19 Treatments

Image of spike protein of SARS-Cov-2 virus is shown with three small antibodies (pink)attached to its receptor binding domains. (From Physics Today, Vol. 73, No. 9, p. 22)

Even as Dotard Donnie - flailing in his re-election bid - dredges up false hopes for a premature Covid vaccine, researchers are hard at work trying to expand the treatment arsenal for dealing with this difficult disease.  As reported in the latest Physics Today (Vol. 73, No. 9, Sept., p. 22) work continues at a feverish pace to find effective treatments.   We already know about remdesavir, but that can't be the only weapon in the arsenal.

Now we learn that researchers at the University of Alberta have reported at the August meeting of the American Crystallographic Association that a "dipeptide- based protease inhibitor used to treat a fatal coronavirus infection in cats also blocks replication of the SARS-Cov-2 virus in samples of monkey lung tissue". Since monkeys are a closer mammal relative to humans than cats, this discloses a promising line of work.

The antiviral  (known as GC273) works by blocking the function of the main protease denoted M ^pro  .  This is an enzyme that cleaves the polyproteins translated from viral RNA into individual proteins, i.e. once it enters human cells.   We also now know, thanks to much more computational work, the sequence of how the viral spike protein attaches to the human cell host cell.

Basically, according to Kerstin Kleese van Dam - Director of Brookhaven National Laboratory's Computational Science Initiative (ibid.):

"When the spike is in its usual down or inward position, it is protected from the immune system.   The spike becomes more vulnerable when it shifts to the up or outward position, required to enter the host cell."

This is good to know as it provides the key to at least controlling the virus using anti-virals.  Indeed, the Alberta team has actually identified a pocket on the spike that changes shape during the transition from down to up.  Also compound screening simulations "uncovered several molecules that might attach to the pocket and  block cell invasion."   According to van Dam:

"It's a bit like wedging a door open."

Joanne Lemieux, a biologist at the University of Alberta, asserts that GC273 has been shown to have no toxic effects on cats.  Now, Anivive - a California company that develops pet medicines - has applied for a U.S. Food and Drug Administration approval to begin human trials with GC273. 

Lemieux's group, after all, crystallized the  M^pro  in combination  with the drug already and produced three-dimensional images (see graphic above) of how it binds strongly to the active pocket on the enzyme. Although GC273 should theoretically be effective in its current form, the Alberta team is planning further crystallography experiments at the Stanford Synchrotron Radiation Lightsource (SSRL) and the Canadian Lightsource to see if a reformulation could be optimized for human use.

What's the advantage?  In the words of one Scripps Research associate, Ian Wilson:

"We'll be able to use smaller crystals, collect higher quality data, get a better signal to noise ratio and collect more data sets per hour."

All of which is badly needed in a media and political environment in which too many false claims are made for cures or treatments (e.g. hydroxychloroquine) and very little can be trusted - especially emanating from the Trump regime.    

What we do know, based on the success of the GC273 research, is that the potential for effective Covid treatments must couple solid experimental and computational efforts as well as strict adherence to scientific testing and confirmation.  We look, therefore, to empirical science to provide answers, not to already damaged politicians like Trump - who will lie or say anything to try to sneak into office again

Indeed, now that he's admitted (on tape) yapping to Bob Woodward that he's a criminal liar and fraud - who deliberately lied to the American people when he knew how deadly the virus is yet downplayed its risk  - it may be all over but the dirges.  At least we can hope so.

See Also:

https://www.folio.ca/antiviral-used-to-treat-cat-coronavirus-could-hold-key-to-covid-19-u-of-a-researchers/

And:

Covid-19 | Donald Trump

Trump’s Lies Cost Tens of Thousands of American Lives — and Bob Woodward Has the Proof on Tape

The Fed Warns Of Economic Calamity If People Don't Change Behaviors - And Dotard Retweets Idiot Quacks

"I know it's true, what that Stella Immanuel said about demons! And I'm gonna retweet it! And yeah, I am a very stable genius!"

"I was probably the healthiest person you ever met. No pre-existing conditions, ski seventy to one hundred days a year.  But I got Covid, had sepsis, had MRSA, had a collapsed lung, and on a ventilator for thirty -one days. Hospitalized for sixty. Loss of blood pressure caused me to lose several fingers. I was on my death bed. This thing is for real, This virus is no joke,"      Greg Garfield,, Covid survivor, this morning on CBS

"It's so fundamental we can't say it enough. Until the virus is contained  the labor market won't be able to fully recover, leaving people in need of support. The path of the economy will depend significantly on the course of the virus."  - Fed Chair Jay Powell, WSJ, 'Business & Investing', p. B12. today.

As we learned this morning that the GDP shrank by 32.9 percent in the previous quarter (see WaPo link at bottom), we are now on notice that we had best change behaviors - or NO  part of the economy is coming back.  The news backed up  Federal Reserve  notices and interviews (over the past 4 weeks)  that if Americans don't collectively get on board in dealing with the virus, we are all for the economic high jump ('Fed's Outlook Grows Gloomier', WSJ, July 28, p. A2).    As noted therein:

"Officials have warned this month in speeches and interviews that the economy faces a deeper downturn and more difficult recovery if the country doesn't take more effective action to slow the spread of infection."

Boston  Fed President Eric Rosengren was even more blunt in his assessment:(ibid.):

"This economy will face severe economic consequences if the public health response doesn't improve."

Adding:

"The Fed's policy response is not going to be able to offset all the losses if we continue to make serious public health mistakes."

This was endorsed by Dallas Fed President Robert Kaplan:

"How well we follow the health care protocols from here is going to be the primary economic tool we have.left."

In other words, the Fed is out of miracle moves to rescue the economy, and this is the crux of the problem - as so eloquently stated by Jay Powell (see top quote). . It's now up to U.S. citizens to get their act together and work together to alter the course of the virus in the U.S.  This instead of engaging in endless mask wars and other self defeating idiocy while buying into fake notions of personal liberty.  We have to understand in this moment of peril our personal freedom has to be sacrificed for the greater communal good.  If we don't grasp that, if we don't act accordingly, you could as well write our epitaph - and not just for the economy.  In addition, the economic disaster coming will almost surely be compounded if a new huge Covid benefits package  (HEROES ACT) isn't passed, and I mean by TODAY!  If that $600/week unemployment extra benefit isn't in the package you can pretty well kiss the GDP and economy goodbye.  GDP depends on spending, and little or none will be done without the enhanced unemployment benefit.  As  financial contributor Jill Schlesinger said on CBS this morning:

"That extra $600 a week was spent in the economy. So without a new package I think we are going to see the economy flatten out." 

Alas, any change in behaviors for the 1 in 4 Americans who think it's all a "plandemic" or "hoax" may be a long way off.  This is given we have a  leader who is totally incompetent in his response to the pandemic, and done everything -including sidelining top medical experts - to ensure the death toll hits hundreds of thousands by November.  Worse, he has now started pandering to a classic crackpot and spreading her idiocy with his retweets.

Maybe Trump  sings the praises of Stella Immanuel -  a Houston pediatrician and demon believer -

because he senses her IQ is as low as his.   Immanuel, leader of Fire Power Ministries,  believes endometriosis and other potentially dangerous gynecological conditions are the residue of sexual intercourse with demons.  Incredibly,  this quack based at  the Rehoboth Medical Center in Houston, also has claimed "alien DNA"  has been used in medical treatments.  (I do hope in none of my prostate cancer treatments, including cryo-freezing of cancer cells back in 2017.  Were these replaced by 'alien DNA'?  Inquiring minds want to know!)

This crackpot quack Immanuel also teaches that demons, known as “spirit husbands” and “spirit wives”, once walked the Earth in physical form. After they drowned in Noah’s flood, however, they carried on only in non-corporeal form. They visit humans in sexy dreams, which aren’t dreams after all but spirit spouses making a booty call. This is almost as cracked as one "minister" (Contessa Adams) once claiming incubi and succubi inhabited sex toys and could possess the humans using them, see e.g.

• BEWARE! Of Sexual Congress with Succubi!

By contrast, Immanuel's  demons are responsible not only for diseases of the female reproductive system but also for male impotence, most financial troubles, marital discord and spiritual malaise.

No, folks, you cannot make this bullshit up.  But this is the sort of irredeemable crappola our  great leader wastes his time tweeting and retweeting.  As well as watching on the tube.  Don't believe it?  You can find Immanuel on Trump’s Twitter feed, where she testifies to the power of hydroxychloroquine - the magic snake oil Dotard and his ass clowns have been humping for months now.   Sadly, millions of Americans heard or saw her advice, thanks in part to the Dotard's amplifying effect,  this before Facebook took down her page and the video (after 20 million views).

Earlier Twitter took down the offending video because (WSJ, July 29, p. A6):

 "It violated its Covid 19 misinformation policy which prohibits misleading claims asserted as fact to influence others' behavior."

In the wake of that a Trump spokesman fulminated (ibid.):

"It is beyond the pale for Twitter to silence the views of medical professionals who happen to dissent from the establishment's anti-hydroxychloroquine  narrative."

But those weren't "medical professionals" but a gaggle of medical quacks and associated hare-brained imbeciles, like Stella Immanuel.  As for the anti-hydroxychloroquine narrative, that is pure bollocks.  The malaria drug has already caused a number of deaths from inappropriate use and the FDA rightly revoked its emergency use authorization.

The most gratuitously odious event from Tuesday's show news conference? Trump asserting Dr. Anthony Fauci "had misled the public"  and also "Fauci and the Democrats perpetuated Covid deaths to hurt Trump."

Fauci fired back squashing the Trump claim.  As far as hurting Trump, the only one who's done that is the Dotard himself, because of his colossally incompetent response to the pandemic.  Tweeting his numskull conspiracy ideations and watching Trump TV when he ought to have been doing all he could to protect American lives.

The Reeptards, including two Colorado idiots now filing a lawsuit  in Fort Collins, to claim masks are "unconstitutional"  and are "political speech" - ought to be forced to see an image of an intubated Herman Cain - before he croaked from Covid.


 Cain, recall, posted a photo of himself at the Trump Tulsa rally, hamming it up with other unmasked goobers.


A pity this lot didn't see Greg Ip's WSJ piece today (p. A2) noting the death rate from Covid 19 is "5 to 40 times deadlier than seasonal flu."

Not that it would have made much difference.  It seldom does to those on the lower end of the IQ (Bell) curve.

See also:

Economy shrinks at fastest quarterly rate on record

And:

Conservatives and the Right | Covid-19

Disease-denying Propaganda Spews a Pandemic of Pandemonium!

by Robert Becker | August 3, 2020 - 6:19am | permalink

And:

Covid-19 | Donald Trump

Trump Storms out after CNN’s Kaitlan Collins Puts Him to Shame for Promoting a Quack Doctor

And:

Covid-19 | Economic Policy | Media

Health Vs. The Economy? It Was Always a Bogus Choice, but the Media Helped Spread It

And:

Covid-19 | European Union

The Pandemic Reveals a Europe More United than the United States

Economy Uber Alles Chauvinists Need To Get A Grip: This COVID Crisis Isn't Ending Any Time Soon

The  "economy over all" pressure purveyors - for anyone who's been reading the reactionary financial press (and even some mainstream media) -  are out in abundance. The common theme of these impatient  Trump trolls,  quack doctors and econ-driven pundits is that we "cannot afford"  to keep the shutdown going (now affecting 41 states with 9 dumbo states still opting out).  The argument is basically a take off on Trump's earlier bilge that the "cure can't be worst than the disease".  Well, uh, yes, it can - if you have a nation that blew every opportunity to get the national outbreak under control. This indeed, is the curse of having Trump & Co. in charge as they've blown it from the get go.  For two weeks downplaying the threat, then  failing to act to get sufficient ventilators, then doing nada - in actually coordinating medical supplies- while the states tried to outbid each other for N95 masks and ventilators.  All this while we beheld a daily spiel full of lies, exaggerations and happy talk designed to lure the stupid and gullible into letting their guards down  See e.g. 

AP FACT CHECK: Trump's misfires on virus death rates, tests

 Even this morning Trump was at it again, lying through his teeth, insisting the federal gov't is rushing supplies to hard hit areas. But notably dismissing an inspector general's report  (released Monday) showing hospitals are lacking critical supplies and dealing with long delays in waiting for coronavirus test results.  As per his M.O. Trump tried to  spin the IG report as "politically biased", never mind it was based on interviews with 323 hospital administrators.  Trump actually said in response to pressure for more testing (CBS, this a.m.): "We're the federal government, we're not supposed to be standing on street corners doing testing."

Actually, sonny, that's pretty close to what you should be doing if you have any intention of getting the economy out of its medically induced coma. Because without testing, without knowing where the virus is - who has it - including the millions who are infected but asymptomatic (and spreading it),  any ambition to reopen the economy is dead in the water.

Even worse, and like your typical snake oil salesman, Trump has been shamelessly pushing the anti-malarial drug hydroxychloroquine, often making  reckless comments literally pulled out of his fat ass.  ("What do ya have to lose?")  The bombastic buffoon even had the temerity to interrupt Dr. Anthony Fauci -  when a reporter at the presser yesterday asked if there was any evidence the drug actually worked on the virus. Dotard,  believing himself to have more expertise than Dr. Fauci, blabbed at the reporter (WSJ, today, p. A4): "Do you know how many times he's answered that question? Maybe 15 times! You don't have to ask that question!" 

But he does need to ask that question,, and of Dr. Fauci himself, when the nation is confronted by this orange maggot's exaggerations and  con man hype day in and day out - at these briefings - which are merely glorified campaign rallies in miniature.  So this human refuse is literally playing with thousands of American lives with his insane narcissistic maneuvers, spinning and refusal to take any responsibility. If we hit the million death mark you can blame this asshole.  See e.g.
Drug pusher Trump has a share in the malaria drug he keeps over-selling for COVID-19

Making matters worse, and effectively acting as accomplices are the numerous pundits, editorial writers and columnists trying to apply pressure to open things up - while downplaying the risks of premature economic moves in any or all states. For example, there is the WSJ's Holman Jenkins, Jr. ('Was Dr. Strangelove an Epidemiologist?')  where he trots out a guy named Joseph A. Ladapo (of UCLA) who claims in a recent op-ed that "the shutdowns if prolonged will only make matters worse."    

Adding that even when restrictions are lifted "we will emerge right back where we started.... and no matter what our hospitals will still be overwhelmed."

Says who?  One is left to wonder where this quack came by that "Eureka" brain fart. But it surely must have made little Holman's own Eureka moment to find such an outlier clown to help him make the case we need to ditch the shutdown ASAP for the sake of our economy. (A position the same day WSJ editorial ('The Shutdown Crash Arrives') vigorously supported, observing "the anti-virus strategy is putting millions out of work"

Sadly, neither the WSJ editors, or Jenkins Jr. or William McGurn (e.g. today) , Kim Strassel and others in that 'hurry up and open the damned country" orbit get it.  That opening prematurely without millions more tests is a colossal fool's errand doomed to backfire, and badly.  In contrast to Jenkins et al at least one WSJ columnist (Greg Ip) seems to get it, writing in his own column ('Uncertain Path of Virus Poses Its Own Risks', p.  A8):  "These days excessive confidence should be greeted with skepticism".

And particularly when used as part of a coordinated PR ploy to push an end to the shutdown (which isn't even nationwide given 9 states are still playing roulette with their residents' lives).  Again. without testing - we are flying blind- and we can't know how many are actually infected in this country, and how many others they are likely infecting and how many hospital beds, ICU space and ventilators will be needed to cover all bases.  As Elizabeth Rosenthal asked in a recent NY Times piece:

How can we know when to reopen society without testing many more people?

The framework for this answer is tied inextricably to the fact that this virus is  not only insidious (in that it can hide among a large segment of the populace who have few or no symptoms) but also the exponential nature of its spread. I.e.

As described by one knowledgeable WSJ columnist ('The Power of Exponential Growth', p. C4, April 4-5):

"Exponential growth is dangerous because if each person infects more than one other person, the spread of disease quickly becomes overwhelming. Multiplying by 3 for instance. it only takes 21 steps to reach 10 billion, more than the current population of the world"(7.75 billion)

Therein lies the key that too few of these econ -pushing pundits, columnists and editorial writers get, and why all the rosy blabber about ending this threat in weeks or months is Pollyannish poppycock.

 Those in search of a  more realistic assessment and answer to Ms. Rosenthal's question can do no better than Zeke Emanuel (oncologist and Vice Provost for Global Initiatives at the Univ. of Pennsylvania)- who put it in stark terms for the economic chauvinists and humpers last night ('Last Word') :

"Realistically COVID -19 will be here at least for the next 18 months or more.  There will be no normalcy until we find a vaccine or effective medications.   I know that's dreadful news to hear. How are people supposed to find work if this goes on in some form for a year and a half?   Is all this economic pain worth trying to stop COVID-19?

The truth is, we have no choice. Prematurely ending the physical distancing and the other measures, the deaths could skyrocket into the hundreds of thousands if not millions. We cannot return to normal  until there's a vaccine. Conferences, concerts, sporting events, religious services, dinner at a restaurant, none of that will resume until we find a vaccine, a treatment or  a cure.

One thing I've learned as a cancer doctor is that it's wrong to paint an overly rosy picture in order to maintain a patient's hope.  Because it fails, it's false.  Biology and disease are formidable opponents that inevitably tell us the truth.  We cannot reieve the oppression of this pandemic until we are realistic. So we need to prepare ourselves for this to last 18 months or more and for the toll it will take, We need to develop a long term solution based on those facts. It has to account for what we are losing as this fight goes on. 

Lawrence, this crisis is not going to go away in a few weeks or when the thirty day plan comes to an end. Although  COVID-19 is affecting us in different ways, and we have to be up to it and fight together.  

When things do open it will probably first be schools because  younger people are more likely to be protected, less likely to die. But that has to be on a voluntary basis. But we can only do that opening when we have testing and the right public health infrastructure.""

The preceding ought to be read and re-read for anyone mesmerized by Trump's  happy talk B.S., false hope blather.   In conjunction with the above, you might also wish to check out the description of this virus'effects on the lungs - by Dr. Kathryn Dreger (NY Times, last week).  Therein she writes:

"It causes a gummy yellow fluid, called exudate, to fill the air sacs, stopping the free flow of oxygen. If only a few air sacs are filled, the rest of the lung takes over. When more and more alveoli are filled, the lung texture changes...  These machines  (ventilators) can’t fix the terrible damage the virus is causing, and if the virus erupts, the lungs will get even stiffer, as hard as a stale marshmallow.

“I feel like I’m trying to ventilate bricks instead of lungs,”  is how one intensive care unit doctor put it.

The heart begins to struggle, begins to fail. Blood pressure readings plummet, a condition called shock. For some, the kidneys fail completely, which means a dialysis machine is also needed to survive. Doctors are left with impossible choices. Too much oxygen poisons the air sacs, worsening the lung damage, but too little damages the brain and kidneys. Too much air pressure damages the lung, but too little means the oxygen can’t get in. Doctors try to optimize, to tweak.....

Even among the Covid-19 patients who are ventilated and then discharged from the intensive care unit, some have died within days from heart damage"

The preceding horrific 'drowning' effects -  and equally desperate treatments -  are worth avoiding even if only a minority of citizens might endure them.  And that means keeping the economy shuttered down - as the sensible Europeans have done  (WSJ, 'Europe Freezes Economy, Willing To Pay  Price',   March 27, p. A9).

The alternative of opening businesses too soon will be too horrible to contemplate and in the end be self-defeating. That's because such premature opening will lead to a second (and likely worse wave) of illness, with an even longer "medically induced coma" for the U.S. economy. 

Our best option now? Follow the lead of the Europeans,  or better  yet, New Zealand, 

Dispatch: New Zealand isn’t just flattening the curve. It’s squashing it.

And not be suckered by the bollocks of either Holman Jenkins, Jr. or his pet toady doc (Ladapo)  willing to provide specious cover for his codswallop. 

See Also:

Trump wants a quick economic recovery, but China’s experience hints at long-lasting problems

And:

Capitalism | Coronavirus

COVID-19 and the Failures of Capitalism

And:

Analysis: At least half of covid-19 patients on ventilators don’t make it

And:

The scope of Trump's unpreparedness is sinking in 

AND::

Donald Trump

A Day Without Donald