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Dennis OConnor

Coronavirus Pandemic Update 37: The ACE-2 Receptor - The Doorway to COVID-19 (ACE Inhib... - 0 views

www.youtube.com/watch

covid research ACE-2

shared by Dennis OConnor on 23 Mar 20 - No Cached
  • Dennis OConnor on 23 Mar 20
     
    "Dr. Michael Kurisu D.O." called this video "molecurlar biology 101" It is from the Youtube Channel: MedCram - Medical Lectures Explained CLEARLY
  • Dennis OConnor on 23 Mar 20
     
    Forwarded to the Project Apollo listserve by "Dr. Michael Kurisu D.O." from Christina Mnatzaganian. This is from the UCSD Family Medicine Faculty Listserve. Hi Deepa, The statement below is from ACC/HFSA/AHA on March 17th. Essentially, there is no human data yet and data is evolving. See below, particularly the red area: *The following joint statement from the ACC, American Heart Association and Heart Failure Society of America was posted online on March 17 and addresses using renin angiotensin aldosterone system (RAAS) antagonists in COVID-19. "The continued highest standard of care for cardiovascular disease patients diagnosed with COVID-19 is top priority, but there are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-I or ARB medications," said Richard J. Kovacs, MD, FACC. "We urge urgent, additional research that can guide us to optimal care for the millions of people worldwide with cardiovascular disease and who may contract COVID-19. These recommendations will be adjusted as needed to correspond with the latest research." Patients with underlying cardiovascular diseases appear to have an increased risk for adverse outcomes with coronavirus disease 2019 (COVID-19). Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, some patients also may have severe cardiovascular damage. Angiotensin converting enzyme 2 (ACE2) receptors have been shown to be the entry point into human cells for SARS-CoV-2, the virus that causes COVID-19. In a few experimental studies with animal models, both angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to upregulate ACE2 expression in the heart. Though these have not been shown in human studies, or in the setting of COVID-19, such potential upregulation of ACE2 by ACE inhibitors or ARBs has resulted in a speculation of potential increased risk for COVID-19 infection in patients with
Dennis OConnor

The proximal origin of SARS-CoV-2 | Nature Medicine - 1 views

www.nature.com/...s41591-020-0820-9

covid research origins-covid-19

shared by Dennis OConnor on 17 Mar 20 - No Cached
  • Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data
  • Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.
  • The receptor-binding domain (RBD) in the spike protein is the most variable part of the coronavirus genome1,2. Six RBD amino acids have been shown to be critical for binding to ACE2 receptors and for determining the host range of SARS-CoV-like viruses7.
  • ...18 more annotations...
  • Theories of SARS-CoV-2 originsIt is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus.
  • the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone
  • we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in an animal host before zoonotic transfer; and (ii) natural selection in humans following zoonotic transfer.
  • COVID-19 were linked to the Huanan market in Wuhan
  • it is likely that bats serve as reservoir hosts for its progenitor
  • Malayan pangolins (Manis javanica) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-221
  • Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled
  • For a precursor virus to acquire both the polybasic cleavage site and mutations in the spike protein suitable for binding to human ACE2, an animal host would probably have to have a high population density (to allow natural selection to proceed efficiently) and an ACE2-encoding gene that is similar to the human ortholog
  • It is possible that a progenitor of SARS-CoV-2 jumped into humans, acquiring the genomic features described above through adaptation during undetected human-to-human transmission.
  • All SARS-CoV-2 genomes sequenced so
  • are thus derived from a common ancestor that had them too
  • Estimates of the timing of the most recent common ancestor of SARS-CoV-2 made with current sequence data point to emergence of the virus in late November 2019 to early December 201923,
  • compatible with the earliest retrospectively confirmed cases
  • Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world27, and there are documented instances of laboratory escapes of SARS-CoV28. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.
  • The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation1
  • it is reasonable to wonder why the origins of the pandemic matter
  • Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events.
  • More scientific data could swing the balance of evidence to favor one hypothesis over another.
Dennis OConnor

What We Know So Far About SARS-CoV-2 - The Atlantic - 0 views

www.theatlantic.com/...608338

covid research testing

shared by Dennis OConnor on 23 Mar 20 - No Cached
  • March 20, 2020
  • One of the few mercies during this crisis is that, by their nature, individual coronaviruses are easily destroyed.
  • These viruses don’t endure in the world. They need bodies.
  • ...30 more annotations...
  • To be clear, SARS-CoV-2 is not the flu. It causes a disease with different symptoms, spreads and kills more readily,
  • his family, the coronaviruses, includes just six other members that infect humans
  • OC43, HKU1, NL63, and 229E—have been gently annoying humans for more than a century, causing a third of common colds
  • MERS and SARS (or “SARS-classic,” as some virologists have started calling it)—both cause far more severe disease.
  • hy was this seventh coronavirus the one to go pandemic?
  • The structure of the virus provides some clues about its success. In shape, it’s essentially a spiky ball. Those spikes recognize and stick to a protein called ACE2
  • This is the first step to an infection
  • he exact contours of SARS-CoV-2’s spikes allow it to stick far more strongly to ACE2 than SARS-classic did
  • But in SARS-CoV-2, the bridge that connects the two halves can be easily cut by an enzyme called furin, which is made by human cells and—crucially—is found across many tissues. “This is probably important for some of the really unusual things we see in this virus,” says Kristian Andersen of Scripps Research Translational Institute.
  • SARS-CoV-2 seems to infect both upper and lower airways,
  • his double whammy could also conceivably explain why the virus can spread between people before symptoms show up
  • All of this is plausible but totally hypothetical; the virus was only discovered in January, and most of its biology is still a mystery.
  • The closest wild relative of SARS-CoV-2 is found in bats, which suggests it originated in a bat, then jumped to humans either directly or through another species.
  • Another coronavirus found in wild pangolins also resembles SARS-CoV-2
  • Indeed, why some coronaviruses are deadly and some are not is unclear. “There’s really no understanding at all of why SARS or SARS-CoV-2 are so bad but OC43 just gives you a runny nose,” Frieman says.
  • Once in the body, it likely attacks the ACE2-bearing cells that line our airways.
  • The immune system fights back and attacks the virus; this is what causes inflammation and fever
  • in extreme cases, the immune system goes berserk
  • These damaging overreactions are called cytokine storms.
  • they’re probably behind the most severe cases of COVID-19.
  • During a cytokine storm, the immune system isn’t just going berserk but is also generally off its game, attacking at will without hitting the right targets.
  • But why do some people with COVID-19 get incredibly sick, while others escape with mild or nonexistent symptoms
  • Age is a factor.
  • other factors—a person’s genes, the vagaries of their immune system, the amount of virus they’re exposed to, the other microbes in their bodies
  • “it’s a mystery why some people have mild disease, even within the same age group,”
  • Coronaviruses, much like influenza, tend to be winter viruses.
  • In the heat and humidity of summer, both trends reverse, and respiratory viruses struggle to get a foothold.
  • irus is tearing through a world of immunologically naive people, and that vulnerability is likely to swamp any seasonal variations.
  • And one recent modeling study concluded that “SARS-CoV-2 can proliferate at any time of year.
  • Unless people can slow the spread of the virus by sticking to physical-distancing recommendations, the summer alone won’t save us.
  • Dennis OConnor on 23 Mar 20
     
    Dr. Michael Kurisu D.O.: We've known about SARS-CoV-2 for only three months, but scientists can make some educated guesses about where it came from and why it's behaving in such an extreme way.
Dennis OConnor

At the Cusp of Solving Cognitive Aging? - Mike Merzenich - Medium - 0 views

medium.com/...g-cognitive-aging-9907a8b7775f

merzenich aging cognition brainHQ

shared by Dennis OConnor on 18 Oct 19 - No Cached
  • Bookmark story
  • the ACTIVE Study.
  • hree different theories
  • ...24 more annotations...
  • memory
  • reasoning
  • speed of processing
  • ACTIVE tracked people for 10 years
  • 74 to 84
  • who would have expected faster cognitive processing speed 10 years later
  • The big question was do those gains transfer to real-world activities.And, the answer is: they do.
  • At the end of 10 years
  • about three years more protection against decline
  • speed training
  • ● 38% less risk of onset of depressive symptoms● 30% less risk of deepening of depressive symptoms● 68% stronger feeling of confidence and control● 48% less risk of at-fault car crashes
  • I (Mike Merzenich) have spent decades studying brain plasticity — the brain’s ability to change (at any age), chemically, structurally and functionally.
  • What changes in the brain as it gets older?
  • basic science question
  • every single thing we measured in the aging brain changed (and none for the better).
  • The top row
  • we built a brain-training program designed to make a rat’s brain faster and more accurate.
  • to improve auditory precision and speed.
  • It turns out that this kind of brain training — continuously and progressively challenging the speed and accuracy of brain processing — improves every aspect of brain health we could measure.
  • we could build, test, refine and validate a training program to improve all the major systems of the brain.
  • plasticity-based training
  • cognition (eg, speed, attention, memory, executive function)
  • quality of life (eg, mood, confidence, self-rated health)
  • dementia?
Dennis OConnor

Milasen: The drug that went from idea to injection in 10 months - 0 views

cen.acs.org/...i42

N-of-One research storytelling

shared by Dennis OConnor on 06 Nov 19 - No Cached
  • itting in freezer at Boston Children’s Hospital is a drug you won’t find anywhere else. It’s called milasen, and the 18 g that the hospital custom-ordered nearly 2 years ago should last for decades. That’s because milasen was designed to treat a single patient—a now 8-year-old girl named Mila Makovec. Milasen was built on decades of work on a class of drugs called antisense oligonucleotides. But after Boston Children’s Hospital scientist Timothy Yu diagnosed Mila with a never-before-seen genetic mutation, he took only 10 months to go from idea to injection. It’s a record-shattering sprint in the typical drug-development marathon, and an unprecedented degree of personalization for a chemical drug.
  • While the story of milasen could be seen as a template for other highly personalized drugs—what the field has come to call n-of-1 therapies—it also raises questions: Who should get these treatments? How will they be funded? And how will the US Food and Drug Administration regulate these projects?
  • Mila’s mom, Julia Vitarello, had started a group called Mila’s Miracle Foundation to raise money to develop a gene therapy for her daughter.
  • ...4 more annotations...
  • Yu was intrigued. He reached out and offered to do whole-genome sequencing on Mila, her parents, and her younger brother.
  • Julia Vitarello, Mila's mother In March, Yu’s team found that a piece of DNA called a retrotransposon—the genetic remnants of viruses scattered throughout all of our genomes—had spontaneously inserted itself in the middle of a noncoding region of Mila’s CLN7 gene.
  • Black told Yu to renegotiate with the FDA. The 3-month safety study in rats, followed by another couple months to report the data, would take too long. After a letter from Vitarello outlining Mila’s decline, the FDA made a concession: Mila could get the drug after just 1 month of testing, so long as the rat studies continued to 3 months to understand any long-term toxicity.
  • Today, Mila continues to get injections of her drug approximately every 2 months. She used to have up to 30 seizures a day, each lasting more than a minute. Now, she only has a few a day, and they don’t last long,
  • Dennis OConnor on 06 Nov 19
     
    "Sitting in freezer at Boston Children's Hospital is a drug you won't find anywhere else. It's called milasen, and the 18 g that the hospital custom-ordered nearly 2 years ago should last for decades. That's because milasen was designed to treat a single patient-a now 8-year-old girl named Mila Makovec. Milasen was built on decades of work on a class of drugs called antisense oligonucleotides. But after Boston Children's Hospital scientist Timothy Yu diagnosed Mila with a never-before-seen genetic mutation, he took only 10 months to go from idea to injection. It's a record-shattering sprint in the typical drug-development marathon, and an unprecedented degree of personalization for a chemical drug."
Dennis OConnor

How to Protect Yourself from COVID-19: Supporting Your Immune System When You May Need ... - 0 views

drhyman.com/...protect-yourself-from-covid-19

covid research immune-system

shared by Dennis OConnor on 21 Mar 20 - No Cached
  • How Can I Protect Myself, My Family, and My Community
  • How to Avoid Infection with COVID-19 
  • How to Support Your Immune System: Remember, Let Food Be Your Medicine! 
  • ...1 more annotation...
  • How to Supplement for Immune Function 
  • Dennis OConnor on 21 Mar 20
     
    Recommended by Erin Raskin, DACM, L.Ac
Dennis OConnor

The Prime Cellular Targets for the Novel Coronavirus - NIH Director's Blog - 0 views

directorsblog.nih.gov/...gets-for-the-novel-coronavirus

research covid

shared by Dennis OConnor on 05 May 20 - No Cached
  • Posted on May 5th, 2020 by Dr. Francis Collins
  • it has been remarkable and gratifying to watch researchers from around the world pull together and share their time, expertise, and hard-earned data in the urgent quest to control this devastating virus.
  • a recent study that characterized the specific human cells that SARS-CoV-2 likely singles out for infection [1
  • ...3 more annotations...
  • This work was driven by the mostly shuttered labs of Alex K. Shalek, Massachusetts Institute of Technology, Ragon Institute of MGH, MIT, and Harvard, and Broad Institute of MIT and Harvard, Cambridge; and Jose Ordovas-Montanes at Boston Children’s Hospital. In the end, it brought together (if only remotely) dozens of their colleagues in the Human Cell Atlas Lung Biological Network and others across the U.S., Europe, and South Africa.
  • The discovery suggests that SARS-CoV-2 and potentially other coronaviruses that rely on ACE2 may take advantage of the immune system’s natural defenses.
  • t’s clear that these new findings, from data that weren’t originally generated with COVID-19 in mind, contained several potentially important new leads. This is another demonstration of the value of basic science.
  • Dennis OConnor on 05 May 20
     
    "Posted on May 5th, 2020 by Dr. Francis Collins"
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