Discussion - 2019-nCoV therapeutics

[Emily]

https://www.fiercebiotech.com/biotech/remdisivir-flop-china-analysts

Did Gilead's remdesivir flop a Chinese trial? Analysts beg to differ
by Amirah Al Idrus |Apr 23, 2020 3:55pm
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The study tested remdesivir in 158 patients, comparing their response to 79 patients in a control group. The treatment “was not associated with a difference in time to clinical improvement,” according to draft documents inadvertently published by the WHO that were seen by Financial Times and Stat and have since been removed. Patients in both study arms experienced side effects at roughly the same rate (about 65%), but more patients on remdesivir stopped treatment early because of side effects compared with placebo (12% versus 5.1%)...

 

[kiwibird]

Remdesivir result also reported here: https://www.thestar.com.my/news/worl...l-report-shows

 

[kiwibird]

https://www.instyle.com/beauty/skin/...ce=twitter.com

“The virus can attach to cell receptors in your upper respiratory tract, allowing it to enter the cell, reproduce, and make you sick,” says Ellen Marmur, M.D., dermatologist and founder of MMSkincare. Spironolactone, a blood pressure medication also prescribed for acne, has been shown in one 2005 study to increase the number of receptors on these cells, essentially creating more entry points for the virus.

https://www.webmd.com/drugs/2/drug-6...e-oral/details

Spironolactone is used to treat high blood pressure and heart failure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to treat swelling (edema) caused by certain conditions (such as heart failure, liver disease) by removing excess fluid and improving symptoms such as breathing problems.

This medication is also used to treat low potassium levels and conditions in which the body is making too much of a natural chemical (aldosterone).

Spironolactone is known as a "water pill" (potassium-sparing diuretic).

https://link.springer.com/article/10...079-018-0466-2

Spironolactone rescues renal dysfunction in obstructive jaundice rats by upregulating ACE2 expression

 

[kiwibird]

Initially I was wondering if health care workers were being hit so hard because they were dehydrated due to not wanting (not being able to) to change their PPE - but this raises a whole bunch of new questions. Nearly every older person I know, who isn't really physically active, takes "water pills"! I wonder what proportion of people take this particular one - and I also wonder if other types of diuretic have the same effect on the receptors...

I also wonder if this has an effect on the clotting that is being reported. ...
" That's the bottom-line message of a new study that shows people on other blood pressure drugs were more than twice as likely to have a stroke than people taking the diuretics known as thiazides."https://www.webmd.com/stroke/news/20010108/water-pill-day-can-keep-stroke-away#1

 

[Shiloh]

New data on Gilead’s remdesivir, released by accident, show no benefit for coronavirus patients. Company still sees reason for hope: https://www.statnews.com/2020/04/23...ent-show-no-benefit-for-coronavirus-patients/

 

[Gert van der Hoek]

First trial for potential Covid-19 drug shows it has no effect


WHO draft put online states remdesivir does not benefit severe coronavirus patients

Remdesivir, a drug thought to be one of the best prospects for treating Covid-19, failed to have any effect in the first full trial, it has been revealed.

The drug is in short supply globally because of the excitement it has generated. It is one of the drugs Donald Trump claimed was “promising”.

In a “gold standard” trial of 237 patients, some of whom received remdesivir while others did not, the drug did not work. The trial was also stopped early because of side-effects.

News of the failure was posted on a World Health Organization clinical trials database, but later removed. A WHO spokesman said it had been uploaded too soon by accident.

 

[kiwibird]

https://www3.nhk.or.jp/news/special/coronavirus/

[FONT="&amp]"Lemdecivir" is a drug under development overseas for the treatment of Ebola hemorrhagic fever, but clinical trials are underway in Japan and overseas as it may be effective against the new coronavirus.[/FONT]​

[FONT="&amp]Regarding the drug, Minister of Health, Labor and Welfare Kato said at a press conference after the Cabinet meeting, "In the current mechanism of approval of drugs, rapid approval is required when urgent use is necessary to prevent the spread of diseases. "There is a system called" special approval "that allows employees to do so" and clarified the policy of utilizing the "special approval" system.[/FONT]​

[FONT="&amp]In order to utilize the "special approval", it is necessary to sell overseas, and Minister Kato said, "If there is an emergency permission to use overseas, we will proceed with the approval examination promptly. We are considering approval in several countries, and we will take action based on the results. "[/FONT]​

 

[Emily]

https://www.sciencetimes.com/articl...-covid-19-scientists-set-test-effectivity.htm

Could Gargling Salt Water Treat COVID-19? Scientists Set to Test Its Effectiveness on COVID-19 Patients
Erika P.Jun 25, 2020 10:48 AM EDT
Gargling salt water is a common remedy to cure illnesses such as colds and coughs, and it is backed with science. Mayo Clinic has identified saltwater gargling as one of the cold remedies that work. Additionally, scientists from the University of Edinburgh in Scotland have confirmed that it can reduce coughs and cold symptoms.

Now they are trying to see if this remedy can treat COVID-19 patients. They want to find out if it could help with mild symptoms of the infection, which infects the airways in a similar manner with common colds and coughs.

They are now recruiting people to take part in their study to test whether gargling with saltwater could boost the body's antiviral abilities.
...
The researchers suggest salt may be used by the cells to create hypochlorous acid, which is bleach commonly known to kill the virus.
....

 

[kiwibird]

https://www.facebook.com/search/top/...epa=SEARCH_BOX

On a day that it is delighted to report no active cases of Covid-19, HM Government of Gibraltar can confirm that the GHA already holds considerable stocks of a drug that has been proven to reduce deaths by up to one-third for the sickest of patients.

Following a medical breakthrough in UK, NHS hospitals have been advised to start using the drug Dexamethasone immediately as there are hopes that it brings a new era of treatment for the disease. The drug costs about 50p per patient per day.

...snip

 

[Emily]

https://www.theguardian.com/world/2...ovid-19-drug-makes-uk-professors-millionaires

Pharmaceuticals industry
'Major' breakthrough in Covid-19 drug makes UK professors millionaires
Synairgen’s share price rises 540% on morning of news of successful drugs trial
Rupert Neate
Fri 24 Jul 2020 11.42 EDT Last modified on Sat 25 Jul 2020 00.12 EDT
...
Richard Marsden, Synairgen’s chief executive, said the company had been deeply involved in a trial using the interferon beta drug to help people with chronic bronchitis or emphysema. “[But] when the coronavirus pandemic emerged, even back in January we realised that we might have an important role to play in defence against this virus,” he said. “So we set about getting a clinical trial set up in February and March in anticipation of the virus coming to the UK, [and] it did. The trial was in place when people started to fill the hospitals up.
...
Results of the initial trial, published this week, showed that coronavirus patients in hospital given a special formulation of the professors’ interferon beta drug, called SNG001, delivered directly to their airways via a nebuliser, were two to three times more likely to recover than those given a placebo.

The study of 101 people found that patients were 79% less likely to develop a severe version of the disease and their breathlessness was also “markedly reduced”, the company said...

 

[sharon sanders]

Dr. Sanjay Gupta

@drsanjaygupta
CNN has confirmed that the United States government is considering a challenge trial as a failsafe or “Plan D” as Dr. Anthony Fauci told me - So what is a challenge trial? 1/16
12:06 AM ? Aug 15, 2020?Twitter Web App
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Dr. Sanjay Gupta

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It is a controversial approach in which healthy people are vaccinated and then intentionally exposed to the virus. The rationale for a challenge trial would be to assess the effectiveness of a vaccine more quickly. 2/16

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Dr. Sanjay Gupta

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The typical approach is to introduce a vaccine trial in an area of the world where virus is circulating rapidly. You need tens of thousands of people enrolled in that part of the trial, known as phase 3. 3/16
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Dr. Sanjay Gupta

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If, for some reason, the virus is no longer adequately circulating, those trials cannot be completed, because there aren’t enough people enrolled. That’s when the challenge trial might be considered. 4/16
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Dr. Sanjay Gupta

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What we’ve learned is the US government is preparing for a potential challenge trial by asking laboratories to submit proposals to create a strain of the novel coronavirus. 5/16

US considering coronavirus strain for potential human challenge trials
The nation's top infectious disease expert, Dr. Anthony Fauci, confirmed to CNN on Friday that scientists at the National Institute of Allergy and Infectious Diseases are working to have a strain of...
cnn.com
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Dr. Sanjay Gupta

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The goal: to create a strain that would be consistent and measurable. That would allow scientists to expose volunteers to a predictable dose of consistent virus, measure their response and compare it to others. 6/16
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Dr. Sanjay Gupta

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More than 100 scientists wrote an open letter to the head of the NIH in July calling for such trials -- but others have voiced ethical concerns. 7/16

Nobel laureates call for 'challenge trials' to speed up vaccine process
More than 100 top scientists including 15 Nobel laureates have written an open letter calling for volunteers to be exposed to the coronavirus to assist with vaccine development.
cnn.com
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Dr. Sanjay Gupta

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“A single death or severe illness in an otherwise healthy volunteer would be unconscionable and would halt progress,” vaccine experts wrote last month. 8/16

Accelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models |...
Perspective from The New England Journal of Medicine — Accelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models
nejm.org




Dr. Sanjay Gupta

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They also said it would be unethical to organize an experiment in which people were deliberately infected unless there was a treatment that can save lives, known as a “rescue drug” -- which does not exist for coronavirus. 9/16
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Dr. Sanjay Gupta

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Also, consider this: challenge trials would likely be done with healthy volunteers -- producing data that might not apply to elderly people and those with pre-existing conditions - some of the most vulnerable to the coronavirus and are prioritized to receive the vaccine. 10/16
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Dr. Sanjay Gupta

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Already more than 33,000 people in 150 countries have signed up to volunteer. 11/16

1 Day Sooner
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Dr. Sanjay Gupta

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But, it would still take time to start a challenge trial, which includes the time it’ll take to create and manufacture a strain of virus they can control. Data would likely not be available until the end of the year. 12/16
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Dr. Sanjay Gupta

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@PeterHotez
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say there’s already enough virus naturally transmitting that we should be able to get answers from the phase 3 trials that are starting to take place. 13/16
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Dr. Sanjay Gupta

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But ethicist Art Caplan says, what if those initial vaccine trials don’t work and we have a limited number of volunteers then “we should be ready to pivot to challenge trials.” 14/16

COVID-19 Human Challenge Trial Debate (hosted by 1Day Sooner, Rikers...
1Day Sooner, Rikers Debate Project, and NYU Langone are collaborating on a virtual debate on the resolution: "COVID-19 human challenge trials involving young...
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Dr. Sanjay Gupta

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Challenge trials have been used for influenza, malaria, typhoid, dengue fever, and cholera in the past. But, typically - rescue medications are available in case someone becomes severely ill. 15/16
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Dr. Sanjay Gupta

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Dr. Anthony Fauci emphasized that they have no intention to use the strain and it would only be for an “absolutely far out contingency.” “Quite frankly, I don’t think this is something we’re going to use,” Fauci said. 16/16

 

[JJackson]

“Quite frankly, I don’t think this is something we’re going to use,” Fauci said.
With 300,000 new cases daily it is hard to see any justification for challenge trials. There are going to be no shortage of hot spots in which to run trials. If you want to do something useful, but with some risk, reduce lab work with live virus to BSL2, with adequate safety provisos, so at least plaque assays can be performed.

 

[Emily]

He's got the perfect background.

https://news4sanantonio.com/news/lo...perimental-covid-19-treatment-using-melatonin
Area doctor sees success in experimental COVID-19 treatment using Melatonin
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Neel, who served on a team of chemical and biological weapons experts for The Pentagon, has studied the effects of Melatonin for years.

"One of my jobs was looking for countermeasures against chemical, biological and radiological weapons," Neel said. "In the course of my research, I came across Melatonin, which is just a remarkable compound," Neel said.

He also graduated with a master's degree in public health from Harvard University.

"I remember being intrigued by the molecule back then," Neel said.

 

[JJackson]

TWiV https://www.microbe.tv/twiv/twiv-766/ has an interesting interview with David Fajgenbaum who was a founder of the CORONA project which has been collating all the off label drugs being used to treat COVID. The data is in a very user friendly searchable database https://cdcn.org/corona-data-viewer/