Coronavirus thread

[learnerpermitted]

Curious what our resident scientists think about the Yan report.

https://zenodo.org/record/4028830

Seems convincing on the surface, but of course everyone has an angle, especially those from Hong Kong.

I have a background in microbiology and my work was very similar to the techniques proposed in the paper. I do not 100% believe COVID19 (aka SARS COV 2) was engineered but the paper does present pretty strong arguments for it. even if this virus was not engineered, the paper ironically does describe how one could.

Some food for thought:
- Viruses can infect a host cell and incorporate its own DNA into the DNA of the host cell and when it chooses to, it can pop its own DNA out of the host DNA, replicate, exit the host cell and infect other cells. Through the process of incorporating and popping out its DNA it can run into errors causing some viral DNA to be left inside the host DNA. The paper talk about this, wish it did.
- Your DNA, bacteria DNA, Eukaryotic DNA, Viral DNA etc by chance can incorporate foreign DNA into its own mainly by homologous recombination or transposable elements, among other mechanisms (wikipedia could explain these mechanisms better than I can). Of course some organisms have mechanisms to prevent it but its not 100% effective. and sometimes viral DNA can incorporate a portion of its own DNA into a host. A possible result of this can be a gain of function from the recipient host. This is known to happen to bacteria.

[Wondering Beard]

Statins Reduce COVID-19 Severity, Likely by Removing Cholesterol That Virus Uses to Infect

"UC San Diego Health researchers recently reported that statins — widely used cholesterol-lowering medications — are associated with reduced risk of developing severe COVID-19 disease, as well as faster recovery times. A second research team at UC San Diego School of Medicine has uncovered evidence that helps explains why: In short, removing cholesterol from cell membranes prevents the coronavirus from getting in."

"A molecule known as ACE2 sits like a doorknob on the outer surfaces of many human cells, where it helps regulate and lower blood pressure. ACE2 can be affected by prescription statins and other medications used for cardiovascular disease.
But, in January 2020, researchers discovered a new role for ACE2: SARS-CoV-2, the coronavirus that causes COVID-19, primarily uses the receptor to enter lung cells and establish respiratory infections."

"While SARS-CoV-2 uses the ACE2 receptor to initially dock on a cell, Rana’s study suggests that the virus also needs cholesterol (normally found in cell membranes) in order to fuse with and enter the cell. 25HC takes away a lot of that membrane cholesterol, preventing viral entry. "

[RoyGBiv]

2020 just keeps on giving.....


Coronavirus mutation emerges that may bypass mask-wearing, hand-washing protections

New strain contains higher loads of the virus, may be more contagious

Scientists in a paper published Wednesday identified a new strain of the virus, which accounted for 99.9 percent of cases during the second wave in the Houston, Texas, area, the Washington Post reported.

[Nephrology]

I have a background in microbiology and my work was very similar to the techniques proposed in the paper. I do not 100% believe COVID19 (aka SARS COV 2) was engineered but the paper does present pretty strong arguments for it. even if this virus was not engineered, the paper ironically does describe how one could.

Some food for thought:
- Viruses can infect a host cell and incorporate its own DNA into the DNA of the host cell and when it chooses to, it can pop its own DNA out of the host DNA, replicate, exit the host cell and infect other cells. Through the process of incorporating and popping out its DNA it can run into errors causing some viral DNA to be left inside the host DNA. The paper talk about this, wish it did.
- Your DNA, bacteria DNA, Eukaryotic DNA, Viral DNA etc by chance can incorporate foreign DNA into its own mainly by homologous recombination or transposable elements, among other mechanisms (wikipedia could explain these mechanisms better than I can). Of course some organisms have mechanisms to prevent it but its not 100% effective. and sometimes viral DNA can incorporate a portion of its own DNA into a host. A possible result of this can be a gain of function from the recipient host. This is known to happen to bacteria.

I'm a little sketched out by some of the language that the authors use. Not exactly the kind of stuff I am used to reading in scientific papers.... eg. " In fact, a ChineseBSL-3lab(the Shanghai Public Health Clinical Centre), which published aNaturearticle reporting a conflicting close phylogenetic relationship between SARS-CoV-2 and ZC45/ZXC21rather than with RaTG1335, was quicklyshut downfor “rectification”36. It is believed that the researchers of that laboratory were being punished for having disclosed the SARS-CoV-2—ZC45/ZXC21 connection""

I also find this really unpersuasive:

". Figure 4 shows the sequence alignment of the Spike proteins from six β coronaviruses. Two are viruses isolated from the current pandemic (Wuhan-Hu-1, 2019-nCoV_USA-AZ1); two are the suspected template viruses (Bat_CoV_ZC45, Bat_CoV_ZXC21); two are SARS coronaviruses (SARS_GZ02, SARS). The RBM is highlighted in between two orange lines. Clearly, despite the high sequence identity for the overall genomes, the RBM of SARS-CoV-2 differs significantly from those of ZC45and ZXC21. Intriguingly, the RBM of SARS-CoV-2 resembles, on a great deal, the RBM of SARS Spike. Although this is not an exact “copy and paste”, careful examination of the Spike-hACE2 structures37,38reveals that all residues essential for either hACE2 binding or protein folding (orange sticks in Figure 3C and what is highlighted by red short lines in Figure 4) are “kept”. Most of these essential residues areprecisely preserved, including those involved in disulfide bond formation (C467, C474) and electrostatic interactions (R444, E452, R453, D454), which are pivotal for the structural integrity of the RBM (Figure 3C and 4). The few changes within the group of essential residuesare almost exclusively hydrophobic “substitutions”(I428àL, L443àF, F460àY, L472àF, Y484àQ), which should not affect either protein folding or the hACE2-interaction. At the same time, majority of the amino acid residues that are non-essentialhave “mutated” (Figure 4, RBM residues not labeled with short red lines). Judging from this sequence analysis alone, we were convinced early on that not only would the SARS-CoV-2 Spike proteinbindhACE2 but also the binding would resemble, precisely, that between the original SARS Spikeproteinand hACE223. Recent structural work has confirmed our prediction39."

This whole paragraph is odd because it sounds like they're saying the AA substitutions should not have any functional consequence on their ability to bind human ACE2. This is weird to me for 3 reasons:

1. If this was a deliberately engineered virus, why would they make changes predicted to have no functional consequence for receptor-ligand interaction?
2. These changes clearly do have functional consequences because they are detected in a strain that now has human trophism
3. Sort of unrelated but a lot of the binding interactions between ACE2 and the spike protein are actually mediated by cell surface glycans and not direct protein-protein interactions.

Overall kind of a strange read. Also doesn't seem to be peer reviewed FWIW.

[EMC]

I'm a little sketched out by some of the language that the authors use. Not exactly the kind of stuff I am used to reading in scientific papers.... eg. " In fact, a ChineseBSL-3lab(the Shanghai Public Health Clinical Centre), which published aNaturearticle reporting a conflicting close phylogenetic relationship between SARS-CoV-2 and ZC45/ZXC21rather than with RaTG1335, was quicklyshut downfor “rectification”36. It is believed that the researchers of that laboratory were being punished for having disclosed the SARS-CoV-2—ZC45/ZXC21 connection""

I also find this really unpersuasive:

". Figure 4 shows the sequence alignment of the Spike proteins from six β coronaviruses. Two are viruses isolated from the current pandemic (Wuhan-Hu-1, 2019-nCoV_USA-AZ1); two are the suspected template viruses (Bat_CoV_ZC45, Bat_CoV_ZXC21); two are SARS coronaviruses (SARS_GZ02, SARS). The RBM is highlighted in between two orange lines. Clearly, despite the high sequence identity for the overall genomes, the RBM of SARS-CoV-2 differs significantly from those of ZC45and ZXC21. Intriguingly, the RBM of SARS-CoV-2 resembles, on a great deal, the RBM of SARS Spike. Although this is not an exact “copy and paste”, careful examination of the Spike-hACE2 structures37,38reveals that all residues essential for either hACE2 binding or protein folding (orange sticks in Figure 3C and what is highlighted by red short lines in Figure 4) are “kept”. Most of these essential residues areprecisely preserved, including those involved in disulfide bond formation (C467, C474) and electrostatic interactions (R444, E452, R453, D454), which are pivotal for the structural integrity of the RBM (Figure 3C and 4). The few changes within the group of essential residuesare almost exclusively hydrophobic “substitutions”(I428àL, L443àF, F460àY, L472àF, Y484àQ), which should not affect either protein folding or the hACE2-interaction. At the same time, majority of the amino acid residues that are non-essentialhave “mutated” (Figure 4, RBM residues not labeled with short red lines). Judging from this sequence analysis alone, we were convinced early on that not only would the SARS-CoV-2 Spike proteinbindhACE2 but also the binding would resemble, precisely, that between the original SARS Spikeproteinand hACE223. Recent structural work has confirmed our prediction39."

This whole paragraph is odd because it sounds like they're saying the AA substitutions should not have any functional consequence on their ability to bind human ACE2. This is weird to me for 3 reasons:

1. If this was a deliberately engineered virus, why would they make changes predicted to have no functional consequence for receptor-ligand interaction?
2. These changes clearly do have functional consequences because they are detected in a strain that now has human trophism
3. Sort of unrelated but a lot of the binding interactions between ACE2 and the spike protein are actually mediated by cell surface glycans and not direct protein-protein interactions.

Overall kind of a strange read. Also doesn't seem to be peer reviewed FWIW.

Thanks for taking the time to parse it out. The simple fact that these hong kong scientists are being funded and promoted by Steve Bannon and his sketchy defector buddy raises red flags for an agenda but I wanted to explore the validity of their scientific claims in more detail because I don't like relying solely on ad-hominem to discredit it.

[Wondering Beard]

Researchers find wide variance in accuracy of COVID-19 antibody tests

[Crow Hunter]

2020 just keeps on giving.....


Coronavirus mutation emerges that may bypass mask-wearing, hand-washing protections

New strain contains higher loads of the virus, may be more contagious

Do we know what the serial number range for this latest version is? I want to make sure my wife and I got the most up to date version of the Rona.


*This is a gun forum after all*

[Crow Hunter]

Statins Reduce COVID-19 Severity, Likely by Removing Cholesterol That Virus Uses to Infect

"UC San Diego Health researchers recently reported that statins — widely used cholesterol-lowering medications — are associated with reduced risk of developing severe COVID-19 disease, as well as faster recovery times. A second research team at UC San Diego School of Medicine has uncovered evidence that helps explains why: In short, removing cholesterol from cell membranes prevents the coronavirus from getting in."

"A molecule known as ACE2 sits like a doorknob on the outer surfaces of many human cells, where it helps regulate and lower blood pressure. ACE2 can be affected by prescription statins and other medications used for cardiovascular disease.
But, in January 2020, researchers discovered a new role for ACE2: SARS-CoV-2, the coronavirus that causes COVID-19, primarily uses the receptor to enter lung cells and establish respiratory infections."

"While SARS-CoV-2 uses the ACE2 receptor to initially dock on a cell, Rana’s study suggests that the virus also needs cholesterol (normally found in cell membranes) in order to fuse with and enter the cell. 25HC takes away a lot of that membrane cholesterol, preventing viral entry. "

Ironically, my wife, even though she is small and petite, has high cholesterol and has recently had to start watching what she eats before they have to put her on a statin. Her mother, who is also small and petite has to take a statin.

I, on the other hand, even when I was obese and didn't fast before a blood panel never got above "normal".

Since starting to eat healthy and losing weight my LDL cholesterol is usually VERY low as is my blood pressure (~100/~60 at 65BPM isn't abnormal for me, I can get it lower.). My LDL cholesterol has actually even been out of range on the low side. During the required consultation after getting the results I asked, so what should I do? They said after a call: "Ummmm…, we don't know, we have never seen that before. Maybe eat a cheeseburger?"

While I am sure that is completely anecdotal and irrelevant it is interesting.

[pangloss]

Regarding sequence mutations: The spike protein is a trimer, so this single mutation (D614G) results in one amino acid change in each monomer. This mutation has been known for a while and there are a number of papers on it. I was on NIH study section a month or two ago, it came up in discussion several times. The 614G virus is absolutely out-competing the "original" version, but from what I've read, the mutation doesn't affect the pathogenicity of the virus, i.e. you're more likely to catch the 614G virus, but your subsequent disease course will probably be about the same. This residue is not on the part of the spike protein that interacts with ACE two (the receptor binding domain), so I'm not sure what the mechanism is underlying the survival advantage.

Years ago I read The Evolution of Infectious Disease by Ewald. The basic premise of the book is that pathogens evolve toward maximal transmission, and that depending on the circumstances, transmission can be maximized by increased OR decreased levels of pathogenicity. Early in the pandemic I tracked Ewald down to write and ask his thoughts on how social distancing measures might select for variant viruses. Disappointingly, he never wrote me back. My expectation for SARS-CoV-2 is that we'll see reduced pathogenicity in favor of prolonged viral shedding or shedding higher titers of virus. If some one is overtly ill, they'll be more like to stay home and distance for others. Peer pressure plays into this because no body wants to hang out with people who have obvious respiratory infections. If a person's symptoms are milder, they are less like to stay home, in which case the virus has more opportunity to find its next host. I think it's a fascinating intersection of human behavior and virology and immunology and evolution.

[Wondering Beard]

Two interesting developments, if they turn out to be correct:

Florida doctors found a coronavirus cure that’s nearly 100% effective

"AdventHealth Ocala doctors treated their patients with a combination of four types of drugs under the acronym ICAM.
ICAM is a COVID-19 therapy designed to boost the immune system while preventing inflammation in the lungs.
A clinical trial is underway to prove the findings. If it’s found to be safe and effective, ICAM therapy might be used on COVID-19 patients without the need to hospitalize them."


Routine blood test may identify patients at risk for severe COVID-19

"The analysis revealed that patients with red cell distribution width, or RDW, above the normal range were nearly three times as likely to die from the disease, the data showed."