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Covid-19 - Treatments & Vaccines

I am about to get on a plane to Vegas for fight night this weekend.

Willing to test this reinfection theory.
 
Remdesivir (log rank death rate ratio vs control [95% CI] = 0.95 [0.81, 1.11]), hydroxychlorquine (1.19 [0.89, 1.59], lopinavir (1.00 [0.79, 1.25]), and interferon-b1a (1.16 [0.96, 1.39]) show no effect on 28-day mortality vs. standard care in large, randomized trial across 30 countries (N = 11,266).

Will read more closely later but it is not yet peer reviewed: https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1



BBC piece on this with some commentary... https://www.bbc.com/news/world-54566730
 
Johnson & Johnson and AstraZeneca vaccine trials cleared to resume testing as of Friday. Stroke of patient in J&J trial deemed not related to vaccine.

Washington Post article
 
NIH scientists find that the corona virus uses a different pathway to exit cells after replication. Most viruses use the biosynthetic secretory pathway. That is, they exit cells the same way hormones, proteins and other molecules made in the cell would leave.

Instead the Corona virus uses the lysosome exocytosis pathway. The lysosome pathway is normally used for removal of unwanted material from the cell. Normally lysosomes are acidified so nothing functional exits. The corona virus is able to prevent this acidification step and exit intact.

The NIH news release has a really good illustration

20201028-lysosome.jpg


Link: https://www.nih.gov/news-events/news-releases/nih-scientists-discover-key-pathway-lysosomes-coronaviruses-use-exit-cells#.X5wI89t1_Ws.link

Because NIH stuff is public domain, here is the whole news release.

Wednesday, October 28, 2020
NIH scientists discover key pathway in lysosomes that coronaviruses use to exit cells

Targeting cells’ ‘trash compactor’ could lead to new antiviral strategy to fight COVID-19.
Illustration of lysosome exocytosis pathway
Illustration shows components of the lysosome exocytosis pathway, which coronaviruses use to exit cells. Also shown are components of the normal biosynthetic secretory pathway. NIH Medical Arts

Researchers at the National Institutes of Health have discovered a biological pathway that the novel coronavirus appears to use to hijack and exit cells as it spreads through the body. A better understanding of this important pathway may provide vital insight in stopping the transmission of the virus—SARS-CoV-2—which causes COVID-19 disease.

In cell studies, the researchers showed for the first time that the coronavirus can exit infected cells through the lysosome, an organelle known as the cells’ “trash compactor.” Normally the lysosome destroys viruses and other pathogens before they leave the cells. However, the researchers found that the coronavirus deactivates the lysosome’s disease-fighting machinery, allowing it to freely spread throughout the body.

Targeting this lysosomal pathway could lead to the development of new, more effective antiviral therapies to fight COVID-19. The findings, published today in the journal Cell(link is external), come at a time when new coronavirus cases are surging worldwide, with related U.S. deaths nearing 225,000.

Scientists have known for some time that viruses enter and infect cells and then use the cell’s protein-making machinery to make multiple copies of themselves before escaping the cell. However, researchers have only a limited understanding of exactly how viruses exit cells.

Conventional wisdom has long held that most viruses—including influenza, hepatitis C, and West Nile—exit through the so-called biosynthetic secretory pathway. That’s a central pathway that cells use to transport hormones, growth factors, and other materials to their surrounding environment. Researchers have assumed that coronaviruses also use this pathway.

But in a pivotal experiment, Nihal Altan-Bonnet, Ph.D., chief of the Laboratory of Host-Pathogen Dynamics at the NIH’s National Heart, Lung, and Blood Institute (NHLBI) and her post-doctoral fellow Sourish Ghosh, Ph.D., the study’s main authors, found something different. She and her team exposed coronavirus-infected cells (specifically, mouse hepatitis virus) to certain chemical inhibitors known to block the biosynthetic pathway.

“To our shock, these coronaviruses got out of the cells just fine,” Altan-Bonnet said. “This was the first clue that maybe coronaviruses were using another pathway.”

To look for that pathway, the researchers designed additional experiments using microscopic imaging and virus-specific markers involving human cells. They discovered that coronaviruses somehow target the lysosomes, which are highly acidic, and congregate there.

That finding raised yet another question for Altan-Bonnet’s team: If coronaviruses are accumulating in lysosomes and lysosomes are acidic, why are the coronaviruses not destroyed before exiting?

In a series of advanced experiments, the researchers demonstrated that lysosomes get de-acidified in coronavirus-infected cells, significantly weakening the activity of their destructive enzymes. As a result, the viruses remain intact and ready to infect other cells when they exit.

“These coronaviruses are very sneaky,” Altan-Bonnet said. “They’re using these lysosomes to get out, but they’re also disrupting the lysosome so it can’t do its job or function.”

The researchers also discovered that disrupting normal lysosome function appears to harm the cells’ immunological machinery. “We think this very fundamental cell biology finding could help explain some of the things people are seeing in the clinic regarding immune system abnormalities in COVID patients,” Altan-Bonnet said. This includes cytokine storms, in which an excess of certain pro-inflammatory proteins in the blood of COVID patients overwhelm the immune system and cause high death rates.

Now that this mechanism has been identified, researchers may be able to find ways to disrupt this pathway and prevent lysosomes from delivering viruses to the outside of the cell; or re-acidify lysosomes in order to restore their normal functions in coronavirus-infected cells so they can fight COVID. The authors have already identified one experimental enzyme inhibitor that potently blocks coronaviruses from getting out of the cell.

“The lysosome pathway offers a whole different way of thinking about targeted therapeutics,” she said, adding that further studies will be needed to determine if such interventions will be effective and whether existing drugs can help block this pathway. She notes the findings could go a long way toward stemming future pandemics caused by other coronaviruses that may emerge.

Research reported in this study was funded by the Division of Intramural Research of NHLBI, part of the National Institutes of Health. Additionally, the research was supported by NIH grants including NIH R01 AI091985-05; NIH R01 NS36592; F32-AI113973; NIH R37GM058615; and NIH R01AI135270. All other co-authors were supported by intramural NIH and National Cancer Institute funds.

Study: β-Coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway DOI: 10.1016/j.cell.2020.10.039

This news release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.
 
Be sure to watch the 2nd 60 Minutes story tonight on the vaccine distribution effort.
Amazing stuff.
 
Be sure to watch the 2nd 60 Minutes story tonight on the vaccine distribution effort.
Amazing stuff.

How did I miss that there's a vaccine to distribute? That's great news! It would be great to get it before school starts in January.
 
thanks donald!

Grow up.....
No one is touting the handling of the pandemic. Watch the damn piece and form your own opinion.
Fact is the mechanism to distribute the vaccine once available is a major undertaking. As a “high risk” individual, it gave me confidence that once available, I have a pretty good shot getting it sooner than later.
No small task for the Pfizer vaccine in particular that will likely require two shots, 21 days apart for it to be effective
 
When do we break it to everyone that we were just using Covid to beat Trump and it's no big deal?
 
When do we break it to everyone that we were just using Covid to beat Trump and it's no big deal?

Have to wait until states certify. That's why it was dumb for people to think it would go away right after election day. There is a process that needs to happen first.
 
Have to wait until states certify. That's why it was dumb for people to think it would go away right after election day. There is a process that needs to happen first.

Word. I just want to make sure all of us elitist libtards are on the same page. I'll keep the mask on for now.
 
Grow up.....
No one is touting the handling of the pandemic. Watch the damn piece and form your own opinion.
Fact is the mechanism to distribute the vaccine once available is a major undertaking. As a “high risk” individual, it gave me confidence that once available, I have a pretty good shot getting it sooner than later.
No small task for the Pfizer vaccine in particular that will likely require two shots, 21 days apart for it to be effective

I watched it - what struck me is that only 60% of physicians surveyed would be willing to take said vaccine and only 40% of nurses would.
 
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