[Pestilence] https://youhavetoliveyour.life/

The Something Awful Forums > Discussion > C-SPAM > [Pestilence] https://youhavetoliveyour.life/

(Thread IKs: PoundSand)

Pingui: Jun 4, 2006; WTF?

NeonPunk posted:

Tbh, I think having tons of antivirals on hand to treat the virus is dumb when it's better to not get infected in the first place.

Sounds like something someone with immune debt would say...

# ? Jan 6, 2024 03:32

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# ? May 26, 2024 00:03

Pingui: Jun 4, 2006; WTF?

Anne Whateley posted:

That the patient is fine and can go back to work, of course

Right, but it certainly isn't telling you that it must be some mystery virus, rather than the most infectious disease ever at the height of a wave.

# ? Jan 6, 2024 03:33

Steve Yun: Aug 7, 2003; I'm a parasitic landlord that needs to get a job instead of stealing worker's money. Make sure to remind me when I post.; Soiled Meat

is Maddy pulling a Walensky

https://x.com/ocnj3/status/1743296992405504223?s=46

# ? Jan 6, 2024 03:36

Pingui: Jun 4, 2006; WTF?

Steve Yun posted:

is Maddy pulling a Walensky
(..)

I don't think so?

I don't know when NPR's transcripts are put up relative to the transmission, but this was put online Thursday: https://www.npr.org/transcripts/1222951956

# ? Jan 6, 2024 03:45

Pittsburgh Fentanyl Cloud: Apr 7, 2003

NeonPunk posted:

Tbh, I think having tons of antivirals on hand to treat the virus is dumb when it's better to not get infected in the first place.

I was on a call at work today and everyone was bullshitting while waiting on a latecomer. One lady talked about how she has covid and is on pax now but they didn't bother asking their kid to isolate because "he's heading back to college anyway," and absolutely everyone on the call except me piped in to talk about how many times they've had covid in the past year and how paxlovid is a wonder drug. absolutely bonkers

# ? Jan 6, 2024 03:46

lumpentroll: Mar 4, 2020

Pittsburgh Fentanyl Cloud posted:

I was on a call at work today and everyone was bullshitting while waiting on a latecomer. One lady talked about how she has covid and is on pax now but they didn't bother asking their kid to isolate because "he's heading back to college anyway," and absolutely everyone on the call except me piped in to talk about how many times they've had covid in the past year and how paxlovid is a wonder drug. absolutely bonkers

lol

# ? Jan 6, 2024 03:48

Pittsburgh Fentanyl Cloud: Apr 7, 2003

i'd rather just not get sick rather than take a pill regimen that can gently caress your liver up but that may just be me

# ? Jan 6, 2024 03:54

ThatBasqueGuy: Feb 14, 2013; someone introduce jojo to lazyb

just booze for killing my liver thanks

# ? Jan 6, 2024 04:08

Soap Scum: Aug 8, 2003

Pittsburgh Fentanyl Cloud posted:

i'd rather just not get sick rather than take a pill regimen that can gently caress your liver up but that may just be me

but if you don't wanna get sick then you can't have applebees

u ever think abt that

# ? Jan 6, 2024 04:23

Dren: Jan 5, 2001; Pillbug

Steve Yun posted:

https://x.com/nateb_panic/status/1743214718402134054?s=46

https://x.com/nateb_panic/status/1743224574840385942?s=46

on one hand I�m extremely jealous

on the other hand these antivirals didn�t stop mass death from happening when they opened up

I saw these posts and I find them extremely weird.

How come we are hearing about this wonderful antiviral plan now, a year after China ended zero covid?

# ? Jan 6, 2024 04:26

trashy owl: Aug 23, 2017

Dren posted:

I saw these posts and I find them extremely weird.

How come we are hearing about this wonderful antiviral plan now, a year after China ended zero covid?

Because it's not in Western media's interests to cover anything but the propaganda angles when it comes to PRC?

# ? Jan 6, 2024 04:33

Rochallor: Apr 23, 2010; ふっっっっっっっっっっっっｃｋ

China created some wonderful new antivirals, but at what cost?

# ? Jan 6, 2024 04:38

RadiRoot: Feb 3, 2007

i got a flut shot and a covid shot. also got blood work. nurse loving sucked so im full of holes. see yall next year.

# ? Jan 6, 2024 04:43

Platystemon: Feb 13, 2012; BREADS

Steve Yun posted:

https://x.com/nateb_panic/status/1743214718402134054?s=46
https://x.com/nateb_panic/status/1743224574840385942?s=46

Azvudine could for the sake of argument be ten times as effective as Paxlovid at preventing every negative outcome of COVID‑19, from PEM to the sniffles to death, and this would still be a dogshit, coping take.

The vast majority of people in China were subjected to Omicron infections, with outdated vaccines as their only protection. They did no better than the West in this regard. The Chinese state did not procure and distribute a billion courses of antivirals.

You can tell me that this antiviral is good, but you cannot tell me that two million people dying was what Xi Jinping had planned all along and an unalloyed victory.

# ? Jan 6, 2024 04:47

Pingui: Jun 4, 2006; WTF?

Dren posted:

I saw these posts and I find them extremely weird.

How come we are hearing about this wonderful antiviral plan now, a year after China ended zero covid?

Yeah, it seems like conspiratorial nonsense. China started developing antivirals and at some point they would inevitably make some, they likely aren't super expensive to make and are probably fairly accessible at this stage. As they should be anywhere, seeing as they likely aren't super expensive to make, compared to the cost to society. That much I think is true.

But the notion that China laid out a strategy with that as the keystone and made some kind of controlled opening is asinine. It seems unlikely and something that would be tooted very loudly, that they had massive quantities laying around ready for the opening. They didn't because they hadn't.

# ? Jan 6, 2024 04:49

Dren: Jan 5, 2001; Pillbug

Insanite posted:

what�s the strength of evidence WRT all of this probiotics biz? slam dunk (beets), or who knows but at least probably harmless (bad beets)?

Dren posted:

Someone posted about S. Salivarius a couple days ago but I don't think the papers were posted directly. This first one is cool because they showed that S. Salivarius expresses proteins that mimic part of the spike, thereby inducing the production of antibodies in the saliva of vaccinated individuals.

Cross-regulation of antibody responses against the SARS-CoV-2 Spike protein and commensal microbiota via molecular mimicry

One of the papers referenced by the first study points out that "the oral cavity is a primary source of the lung microbiota community" therefore it stands to reason that the oral probiotic is beneficial to the lung as well, though antibodies in the lung were not measured in the first study. They also point out that S. Salivarius has been "widely clinically investigated especially for its effective action in contrasting ear, oral, pharyngeal, and tonsillar infections caused by S. pyogenes, S. pneumoniae, M. catarrhalis, and/or H. influenzae." Which sounds great.

Clinical Effects of Streptococcus salivarius K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study

Another referenced paper is The administration of S. salivarius K12 to children may reduce the rate of SARS-CoV-2 infection, where 128 schoolchildren in Milan were enrolled in a study where half were given S. Salivarius for 90 days (this was pre-vaccine) and they were swabbed for covid if they showed any symptoms or had any reported exposures. There were 0 covid cases in the S. Salivarius group and 24 in the control group! And that is pre-vaccine! The authors of the first paper noted that there were some cross-reactive antibodies in unvaccinated mice so maybe some people have those too, or maybe there is some other mechanism.

Safety Assessment of the Oral Cavity Probiotic Streptococcus salivarius K12 addresses the safety of S. Salivarius.

I have started taking a lozenge once a day. This seems much better evidence than the nasal spray stuff since they've directly measured how it increases production of spike protein binding antibodies in the saliva and it is highly likely to do that in the lungs too. The recent nature article about inhaled vaccines noted that delivery to the trachea seemed more efficacious than delivery to the upper nasal cavity, which kinda makes sense since the lungs is where sars-cov-2 gets ya.

# ? Jan 6, 2024 04:50

Gunshow Poophole: Sep 14, 2008; OMBUDSMAN
POSTERS LOCAL 42069; Clapping Larry

Platystemon posted:

Azvudine could for the sake of argument be ten times as effective as Paxlovid at preventing every negative outcome of COVID‑19, from PEM to the sniffles to death, and this would still be a dogshit, coping take.

The vast majority of people in China were subjected to Omicron infections, with outdated vaccines as their only protection. They did no better than the West in this regard. The Chinese state did not procure and distribute a billion courses of antivirals.

You can tell me that this antiviral is good, but you cannot tell me that two million people dying was what Xi Jinping had planned all along and an unalloyed victory.

Yup

I guarantee China is just as loving dumb as any other nation state captive to capital about every aspect of covid. The government chose a path that was relevant At All for as long as they chose it, and as soon as they stopped doing so, it became irrelevant.

There is literally no way forward on covid that doesn't involve either a miracle accident of biochemistry, or an international orientation and exercise of power and its crystallization in money that is unprecedented in the modern age. impossible in the current idiom.

# ? Jan 6, 2024 05:09

Zantie: Mar 30, 2003; Death. The capricious dance of Now You Stop Moving Forever.

I keep forgetting to post the sequencing updates here each week.

JN.1* is squeezing out the soup of subvariants with the FLiP mutation along with everything else.

XDA (recombinant of XBB.1.16 and HN.5, nothing that peculiar) recently popped back up. It was originally seen in a group of samples sequenced out of Spokane county right after Thanksgiving, though now it's spread out and seen as far as King county. The metadata indicates these are from baseline surveillance/random sampling, not from an outbreak/cluster which is interesting. I doubt it'll hold up against JN.1* though.

Recent changes due to backfill:

# ? Jan 6, 2024 05:45

Pillowpants: Aug 5, 2006

Number go up

# ? Jan 6, 2024 06:31

Steve Yun: Aug 7, 2003; I'm a parasitic landlord that needs to get a job instead of stealing worker's money. Make sure to remind me when I post.; Soiled Meat

variant proportion chart is always going to look like a shepherd tone waveform

# ? Jan 6, 2024 06:39

SixteenShells: Sep 30, 2021

any word on issuing another round of covid tests?

# ? Jan 6, 2024 06:44

Platystemon: Feb 13, 2012; BREADS

This guy is stupid and evil and overqualified to be the dean of medicine at the University of California at San Francisco.

Everyone in public health should be facepalming when they see that kind of behavior.

# ? Jan 6, 2024 09:01

Snowglobe of Doom: Mar 30, 2012; sucks to be right

I just spotted someone dicknosing a flomask. :psyduck:

It was pulled down half off her face.

I also spotted someone wearing a 3M elastomeric respirator, I think that was only the second time I've seen one in Melbourne

# ? Jan 6, 2024 09:14

shazbot: Sep 20, 2004; Ah, hon, ya got arby's all over my acoustic wave machine.

when I was in the hospital I tried to wear an n95 except when eating/taking pills, but when they gave me oxy every 4 hours that mask became the last thing I was concerned about.

what I�m saying is maybe that guy was railing opioids in the lavatory.

# ? Jan 6, 2024 09:14

Oracle: Oct 9, 2004

Platystemon posted:

This guy is stupid and evil and overqualified to be the dean of medicine at the University of California at San Francisco.

Everyone in public health should be facepalming when they see that kind of behavior.

I think it depends on which �half� of the flight the guy is referring to. If it�s the half that is happening during sitting at the gate, taxiing and taking off/landing, then the guy is following widely reported best practices as shown in mass media (�airplanes have great air exchange and ventilation once airborne, it�s only during taxiing and at the gate that it gets bad, you should mask then if you�re worried about catching diseases�). If he�s just randomly doffing it for no apparent reason then sure, he�s yet another �mask=talisman of +2 vs disease if in possession� dipshit.

# ? Jan 6, 2024 09:21

Oracle: Oct 9, 2004

Snowglobe of Doom posted:

I just spotted someone dicknosing a flomask. It was pulled down half off her face.

I also spotted someone wearing a 3M elastomeric respirator, I think that was only the second time I've seen one in Melbourne

I still see people dicknosing N95s. While the straps are still on their heads. I cannot comprehend this, it�s literally less comfortable than either wearing it correctly or just letting it hang around your neck.

# ? Jan 6, 2024 09:25

maxwellhill: Jan 5, 2022

maybe he was already sick and sitting next to the twitter person for long enough made them decide to let loose and infect them

# ? Jan 6, 2024 09:31

genericnick: Dec 26, 2012

Platystemon posted:

Azvudine could for the sake of argument be ten times as effective as Paxlovid at preventing every negative outcome of COVID‑19, from PEM to the sniffles to death, and this would still be a dogshit, coping take.

The vast majority of people in China were subjected to Omicron infections, with outdated vaccines as their only protection. They did no better than the West in this regard. The Chinese state did not procure and distribute a billion courses of antivirals.

You can tell me that this antiviral is good, but you cannot tell me that two million people dying was what Xi Jinping had planned all along and an unalloyed victory.

Do we actually have reasonable estimations now? I think we had 1.5 million estimated from what went down in HK before, but I don't remember anything since then.

# ? Jan 6, 2024 12:42

genericnick: Dec 26, 2012

Pingui posted:

Yeah, it seems like conspiratorial nonsense. China started developing antivirals and at some point they would inevitably make some, they likely aren't super expensive to make and are probably fairly accessible at this stage. As they should be anywhere, seeing as they likely aren't super expensive to make, compared to the cost to society. That much I think is true.

But the notion that China laid out a strategy with that as the keystone and made some kind of controlled opening is asinine. It seems unlikely and something that would be tooted very loudly, that they had massive quantities laying around ready for the opening. They didn't because they hadn't.

Seems like you would not deconstruct your test infrastructure if your new strategy was distributing anti-virals to infected.

# ? Jan 6, 2024 12:43

Pingui: Jun 4, 2006; WTF?

genericnick posted:

Seems like you would not deconstruct your test infrastructure if your new strategy was distributing anti-virals to infected.

Yup, everything we've seen from China in this regard indicates that they lost control, let it rip and then put a lid on tracking. Effectively speedrunning the "strategy" of the West.

Edit: Also sorry that my last post was such a mess, I should not be posting that late jfc.

Pingui has issued a correction as of 13:00 on Jan 6, 2024

# ? Jan 6, 2024 12:55

Pingui: Jun 4, 2006; WTF?

Cut out the cope, as otherwise Topol is right.

https://www.latimes.com/opinion/story/2024-01-04/covid-2024-flu-virus-vaccine posted:

Opinion: The U.S. is facing the biggest COVID wave since Omicron. Why are we still playing make-believe?

The pandemic is far from over, as evidenced by the rapid rise to global dominance of the JN.1 variant of SARS-CoV-2. This variant is a derivative of BA.2.86, the only other strain that has carried more than 30 new mutations in the spike protein since Omicron first came on the scene more than two years ago. This should have warranted designation by the World Health Organization as a variant of concern with a Greek letter, such as Pi.

By wastewater levels, JN.1 is now associated with the second-biggest wave of infections in the United States in the pandemic, after Omicron. We have lost the ability to track the actual number of infections since most people either test at home or don�t even test at all, but the very high wastewater levels of the virus indicate about 2 million Americans are getting infected each day.

In several countries in Europe, wastewater levels reached unprecedented levels, exceeding Omicron. Clearly this virus variant, with its plethora of new mutations, has continued its evolution with mutations adapted for infecting or reinfecting us.
(..)
All of this is occurring on top of the flu and RSV waves, both of which are at very high levels, not clearly having peaked yet, with some people experiencing two of these infections at once.

With all three respiratory viruses circulating at full force, you would think we�d be seeing people wearing masks everywhere in public. That couldn�t be further from the truth. The state of denialism and general refusal to take simple steps to reduce the risk of infection can be seen everywhere.

It has taken healthcare systems many weeks after JN.1 showed up in October to recognize the threat. Only very recently have some reinstated mask mandates for healthcare workers and patients. Little has been done across the country to improve indoor air quality, upgrading filtration and ventilation.

Now in its fifth year, SARS-CoV-2 has once again proved to be highly resilient, capable of reinventing itself to infect us. Yet we continue to make-believe that the pandemic is over, that infections have been transformed to common cold status by prior exposure(s), and that life has returned to normal. Sadly, none of this is true.

The massive number of infections in the current wave will undoubtedly lead to more people suffering from long COVID. For a high proportion of people, especially those of advanced age, immunocompromised or with coexisting conditions, getting COVID is nothing close to a straightforward respiratory infection.

What is the exit strategy that could get us to �return to normal�? It certainly can�t happen with the current complacency and false belief that the virus will burn out and go away. Inevitably, there will be another strain in the future that we are not at all prepared for and will lead to yet another very big wave across the planet.
(..)
It�s crickets from the White House on COVID now, with no messaging on getting the updated booster or masking. The Biden administration has done far too little to accelerate research on effective treatments for long COVID.

This passivity reinforces the illusion that the pandemic is behind us when it�s actually raging. And this season will be followed by a more quiescent period, which will, once again, lull us into thinking the pandemic is over. But there is no getting over it until we recognize reality and double down on the research that will allow us to block infections and virus spread, and achieve lasting, variant-proof immunity.

# ? Jan 6, 2024 13:46

Platystemon: Feb 13, 2012; BREADS

I love that �Omicron� is tacitly acknowledged to be something that is now in the past, and what we are going through now is different. It�s not just Topol doing it.

A person would not write that �Starsector is the greatest videogame since the twenty‐first century�. They�d have to go with either �since the dawn of the twenty‐first century� or �since the twentieth century�.

# ? Jan 6, 2024 13:59

Zugzwang: Jan 2, 2005; You have a kind of sick desperation in your laugh.; Ramrod XTreme

Pingui posted:

Cut out the cope, as otherwise Topol is right.

I sure hope things are quieter when Wifezwang and I are having kid #2 in the hospital next month.

# ? Jan 6, 2024 14:25

Pingui: Jun 4, 2006; WTF?

This is insanely cool.
"A stapled lipopeptide platform for preventing and treating highly pathogenic viruses of pandemic potential"

https://www.nature.com/articles/s41467-023-44361-1 posted:

Abstract
The continued emergence of highly pathogenic viruses, which either thwart immune- and small molecule-based therapies or lack interventions entirely, mandates alternative approaches, particularly for prompt and facile pre- and post-exposure prophylaxis. Many highly pathogenic viruses, including coronaviruses, employ the six-helix bundle heptad repeat membrane fusion mechanism to achieve infection. Although heptad-repeat-2 decoys can inhibit viral entry by blocking six-helix bundle assembly, the biophysical and pharmacologic liabilities of peptides have hindered their clinical development. Here, we develop a chemically stapled lipopeptide inhibitor of SARS-CoV-2 as proof-of-concept for the platform. We show that our lead compound blocks infection by a spectrum of SARS-CoV-2 variants, exhibits mucosal persistence upon nasal administration, demonstrates enhanced stability compared to prior analogs, and mitigates infection in hamsters. We further demonstrate that our stapled lipopeptide platform yields nanomolar inhibitors of respiratory syncytial, Ebola, and Nipah viruses by targeting heptad-repeat-1 domains, which exhibit strikingly low mutation rates, enabling on-demand therapeutic intervention to combat viral outbreaks.

The research article is pretty esoteric, so here is a news article laying it out in a more layman accessible manner (I suspect it is a major development and this is Saturday, so have the entire thing with all the bells and whistles):
"Novel compound protects against infection by virus that causes COVID-19, preliminary studies show"

https://medicalxpress.com/news/2024-01-compound-infection-virus-covid-preliminary.html posted:

_{a Schematic of the six-helix bundle (6-HB) fusion mechanism of SARS-CoV-2 and the mechanism by which a stapled lipopeptide decoy of the HR2 domain disrupts 6-HB assembly and thus blocks viral entry. b Structure of the SARS-CoV-2 6-HB assembly (PDB ID 7TIK), with the HR2 domain that formed the basis for stapled lipopeptide designs colored in red. c Compositions of the i, i + 7 staple scanning library of HR2 amino acid sequences 1168-1205 with the structure of the PEG₄-thiocholesterol moiety appended to the C-terminal lysine. WT, unstapled lipopeptide bearing the indicated wild-type HR2 domain sequence. d�h The stapled lipopeptide library was tested in infectivity assays using a series of pseudoviruses (PV), including the initial Wuhan-Hu-1 strain (d), Omicron variants B.1.1.529.1 (e) and B.1.1.529.2 (f), and SARS-CoV Urbani (g) in ACE2-expressing HEK293T cells, and SARS-CoV-2 Beta strain live virus (h) in ACE2-A549 cells at screening doses of 250 nM (e, f), 500 nM, (d, g) or 4 μM (h). The data are normalized to the percent infected cells treated with vehicle control. Data are mean � SEM for assays performed in technical quadruplicate (PV) or triplicate (LV) and then repeated with similar results. The gray shading highlights those lipopeptides that inhibited infectivity to <25% of infected cells (data points colored red). i A full dose-titration of the consistently best-performing hit, designated Stabilized Alpha-Helix of SARS-CoV-2 HR2 bearing the D staple and PEG4-thiocholesterol (SAH-HR2-D-PEG4-TC), in an expanded panel of pseudoviral assays, which included Wuhan-Hu-1, D614G, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.1.529.1 (Omicron), SARS-CoV (Urbani), and VSV-G as a specificity-of-action control. Data are mean � SEM for assays performed in technical quadruplicate and then repeated with similar results. IC50 values were calculated by nonlinear regression analysis of the dose-response curves.}

Compounds that obstruct the "landing gear" of a range of harmful viruses can successfully protect against infection by the virus that causes COVID-19, a study led by Dana-Farber Cancer Institute scientists shows. Based on the findings, researchers have launched a human clinical trial of one such compound made by chemically stabilizing a key coronavirus peptide.

If the compound, called a stapled lipopeptide, proves effective as a nasal spray in the trial, it could be the basis for a new drug modality to prevent or treat COVID-19, say the authors of the study, posted online Jan. 4 in the journal Nature Communications.

Because such compounds foil a mechanism many viruses use to enter and infect cells, stapled lipopeptides may also be effective against dangerous and potentially deadly viruses such as RSV, Ebola, and Nipah, as the authors demonstrate in their study.

"Although vaccines, monoclonal antibodies, and small molecule drugs have played a crucial role in protecting people from life-threatening COVID-19 infection, there remains a critical gap in the treatment arsenal," said Loren Walensky, MD, Ph.D., Physician and Principal Investigator, Linde Program in Cancer Chemical Biology at Dana-Farber/Boston Children's Cancer and Blood Disorders Center.

He led the research with Gregory Bird, Ph.D., of Dana-Farber, and Robert Davey, Ph.D., of Boston University's National Emerging Infectious Diseases Laboratories (NEIDL).

"The constant evolution of the virus and the emergence of new variants has markedly decreased the effectiveness of immune-based approaches, requiring periodic reformulation of vaccines. What has been missing are fast-acting, easy-to-administer, and resistance-proof agents that can be used before or after exposure to the virus to prevent infection or reduce symptoms directly. Our study is an encouraging indication that stapled lipopeptides offer that potential," Walensky added.

"It was exciting to see how these peptides, which work by jamming the gears of the virus infection machine, moved quickly from a basic idea on paper to being effective with the viruses and in real disease models," said Robert Davey, Ph.D., Professor, Microbiology at Boston University's NEIDL.

"This was a great collaboration that started in the very first days of the pandemic when we wanted to work out a treatment for SARS-CoV-2 using the great biocontainment resources we have at Boston University. Our two labs worked very well together, and this is something we will continue to do in the future on other viruses that I work on, like Ebola."

Unlike mRNA vaccines, which are a form of immune-based therapy that provides delayed protection and also requires periodic administration due to viral mutation and/or waning immunity, the stapled lipopeptides developed by Walensky's lab act directly on SARS-CoV-2, the coronavirus responsible for COVID-19, interfering with its ability to infect healthy cells.

Because this approach does not use the immune system as an intermediary, it is especially promising for people with weakened immune systems, either due to their disease or treatment with immunosuppressive agents, such as chemotherapy.

Walensky's lab has pioneered developing and applying stapled peptides for nearly 20 years. These unique agents consist of natural peptides�a stretch of amino acids in a defined sequence�whose bioactive structure is chemically stabilized by an installed "staple" and, in this case, further linked to a lipid, which is believed to help concentrate the stapled peptide at the site of viral infection�the membrane surface of the otherwise healthy cell.

The new study shows that stapled lipopeptides are exceptionally stable, resisting extremes of temperature and chemical conditions, an important feature for persistence both inside and outside the body. The design strategy not only prevents peptide degradation in the body upon administration but also remedies prior challenges with shipment and storage, such as the required cold chain for COVID-19 vaccines.

In 2010, Walensky's lab first developed double-stapled peptides that target the same key step in the process by which the human immunodeficiency virus (HIV) binds to and then infects human cells, causing AIDS.

The stapled peptides mimicked the virus's "landing gear," a bundle of six coils or "helices" of the virus that comes together, enabling the virus to fuse with the host cell's membrane.

The therapeutic approach, known as fusion inhibition, prevents the virus from entering the cell to off-load its nucleic acid blueprint, otherwise turning it into a virus-producing factory. The stapled peptide, which mimics one of the coiled regions, disrupts the formation of the fusion apparatus, halting infection at its source.

In 2014, Walensky's team developed analogous stapled peptides targeting this same feature of the RSV virus, which can cause severe respiratory illness and even respiratory failure in the elderly and very young alike. They showed that administering the stapled peptide as a nose drop could prevent RSV infection in mice and also prevent the spread of established nasal infection from migrating to the lungs.

When the COVID-19 pandemic broke out in early 2020, Walensky's lab promptly converted one of the coiled motifs of the SARS-CoV-2 six-helix bundle into a stapled peptide in an effort to develop a therapeutic for pre- and post-exposure prophylaxis.

"Remarkably, the viral peptide sequence that we use to block the fusion apparatus is 100% identical between SARS-CoV-2 and SARS1, which emerged as a deadly respiratory virus in 2003," notes Walensky. He points out that, in contrast to the viral sequences that frequently mutate to evade immune-based therapies, the virus's fusion sequences are rarely altered due to the critical role of six-helix bundle assembly in promoting viral infection.

In cooperation with researchers experts in highly pathogenic viruses at the NEIDL, Walensky's team began developing dozens of stapled peptide fusion inhibitors for anti-viral testing, altering the location of the staple and the linker between the staple and the lipid to determine which version worked best against the broadest spectrum of SARS-CoV-2 variants.

Ironically, as the virus evolved to evade vaccines and monoclonal antibodies, the more effective the stapled lipopeptides became, owing to the essential nature of the fusion mechanism they target.

Then, in partnership with the laboratory of Richard Bowen, DVM, Ph.D., of Colorado State University and the newly formed Red Queen Therapeutics of Cambridge, Massachusetts, that licensed the Dana-Farber technology, the Walensky lab began testing the inhibitors in hamsters. The studies evaluated a lead-stapled lipopeptide as a preventive and therapeutic agent. The animals were randomly selected to receive an inhibitor before and/or after nasal inoculation with SARS-CoV-2.

The results were very encouraging, Walensky remarks. The animals in each group that received the inhibitor maintained their weight, an indication that they remained well despite viral exposure. Examination of their noses showed a relative drop in viral titers compared to the untreated control group, and evaluation of their lung tissue found that the animals were significantly protected from severe pneumonia, a common complication of COVID-19.

"Similar to what we saw with RSV, nasal treatment with a stapled peptide fusion inhibitor�even if given after inoculation with SARS-CoV-2�prevented the infection from adversely affecting the lungs and causing severe disease," Walensky comments.

A second set of studies explored whether the inhibitors could help reduce transmission of the virus from one hamster to another. Again, the results were encouraging. "Animals that weren't treated consistently lost weight. Those that received treatment, either before or after exposure to an infected hamster, preserved their weight," Walensky notes. Correspondingly, viral loads in the noses and lungs of treated animals were lower than in untreated animals.

The fact that many viruses with pandemic potential rely on the six-helix bundle to enter and infect cells suggests that stapled lipopeptides developed by Walensky's lab can be adapted to block or reduce infection by other viruses "on demand."

"Red Queen Therapeutics was founded on the conviction that this novel technology from the Walensky lab would be broadly applicable in successfully combating viral threats, using a pre- and post-exposure prophylaxis paradigm, and COVID presents a proving ground as well as an important opportunity in its own right," said Ron Moss, M.D., CEO of Red Queen Therapeutics. "We are excited to validate data in this publication with our human trials in SARS-CoV-2 now under way and anticipate having data to share later this quarter," he added.

"This approach has the potential to fill an important gap in our arsenal against COVID-19 and other viruses that cause severe respiratory and hemorrhagic diseases," Walensky said.

"Imagine being able to protect yourself from COVID-19 or other disruptive respiratory viruses with a simple nasal spray that you could use to avoid infection at a large gathering or after exposure to a close contact who turns out to test positive for SARS-CoV-2. That is the promise this work holds, not only for otherwise healthy individuals, but especially for immunocompromised patients who remain most at risk of severe infection."

# ? Jan 6, 2024 14:55

Hellequin: Feb 26, 2008; You Scream! You open your TORN, ROTTED, DECOMPOSED MOUTH AND SCREAM!

Steve Yun posted:

https://x.com/lauramiers/status/1743375993669087302?s=46

https://x.com/dbdugger/status/1687179030091497472?s=46

fellas is Paxlovid garbage and should infected people be seeking out these �repurposed hiv drugs� instead

https://x.com/lauramiers/status/1743423698864853049?s=46

I somehow missed the �covid causes more T cell loss than HIV� train from 2022

Dugger is a complete loving crank who has absolutely no idea what he's talking about. He's somehow leveraged his HIV status and the fact that he writes hospital billing (and bail bond) software as some kind of medical expertise, he's currently selling assessments on his website for neurodegeneration based on a similar test they give to like terminal AIDS patients. His other crusades are claiming Paxlovid will destroy your liver and kidney functions immediately and attacking ME/CFS patients/advocates/researchers as condemning people to dementia for making comparisons between long covid and ME/CFS and not buying into his "SARS Associated Neurological Decline" (his term) theory. If you ever actually dig into any of his threads it becomes obvious he's got no idea what he's talking about, he'll repeat the same half-truths and weird phrases regardless of context and just say some really loving odd things. The guy is a toxic element, he should be laughed out of the room and frankly the size of his platform is disturbing.

Hellequin has issued a correction as of 05:13 on Jan 7, 2024

# ? Jan 6, 2024 15:03

Gunshow Poophole: Sep 14, 2008; OMBUDSMAN
POSTERS LOCAL 42069; Clapping Larry

Platystemon posted:

This guy is stupid and evil and overqualified to be the dean of medicine at the University of California at San Francisco.

Everyone in public health should be facepalming when they see that kind of behavior.

everyone in public health after the last four years is an active collaborator

# ? Jan 6, 2024 15:57

Steve Yun: Aug 7, 2003; I'm a parasitic landlord that needs to get a job instead of stealing worker's money. Make sure to remind me when I post.; Soiled Meat

https://x.com/inkblue01/status/1743621868454580685?s=46

# ? Jan 6, 2024 16:13

A Bag of Milk: Jul 3, 2007; I don't see any American dream; I see an American nightmare.

Steve Yun posted:

https://x.com/inkblue01/status/1743621868454580685?s=46

When I tell people I dodged covid when my wife had it by sleeping on the couch and masking indoors for two weeks the response is generally some flavor of "wow good for you, also I would never do that because too much effort." Maddening

# ? Jan 6, 2024 16:54

Oracle: Oct 9, 2004

A Bag of Milk posted:

When I tell people I dodged covid when my wife had it by sleeping on the couch and masking indoors for two weeks the response is generally some flavor of "wow good for you, also I would never do that because too much effort." Maddening

Yep.

# ? Jan 6, 2024 16:56

Adbot: ADBOT LOVES YOU

# ? May 26, 2024 00:03

Pingui: Jun 4, 2006; WTF?

Just for the headline :negative:

https://www.syracuse.com/health/2024/01/covid-is-spiking-again-in-syracuse-hospitals-but-thats-the-new-normal-doc-says.html posted:

Covid is spiking again in Syracuse hospitals, but that�s the new normal, doc says

# ? Jan 6, 2024 16:59

The Something Awful Forums > Discussion > C-SPAM > [Pestilence] https://youhavetoliveyour.life/

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