Sciencemadness Discussion Board

Handbook of COVID-19 Prevention and Treatment

Mush - 21-3-2020 at 10:03

Handbook of COVID-19 Prevention and Treatment

https://covid-19.alibabacloud.com/



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andy1988 - 21-3-2020 at 16:02

Some links/papers I have to share:
Coronavirus drugs: Who's doing what, and when they might come
Special report highlights potential therapeutic agents, vaccines for COVID-19 Which links to the paper: https://pubs.acs.org/doi/10.1021/acscentsci.0c00272#
https://www.who.int/blueprint/priority-diseases/key-action/n...
https://www.who.int/emergencies/diseases/novel-coronavirus-2...

A risk of vaccine development, unintended consequences: Urgently needed: New way to combat vaccine-derived poliovirus

An old paper I read talked a bit about the trouble of making a coronavirus vaccine, impairing the spike protein crippled the virus but it made for a poor vaccine in tests. Not worth sharing I guess. For this reason I particularly like the vaccine being made by Moderna who are using a replica model of the SARS-CoV-2 spike protein.

I particularly like the research on inhibitors of the spike protein:
10 Apr 2019 a group modeled the spike protein of many coronaviruses and found a short peptide which would inhibit many of them, meant to be a "broad spectrum" anti-coronavirus therapeutic, tested in vivo in a mouse model, delivered intranasally, and coined their short peptide "EK1": A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike | Science Advances (Figure 1(D) shows the broad inhibition and concentration of the peptide, and Figures 4-6 give you a visual on how the inhibition works)
11 February 2020 this group reused their workflow for SARS-CoV-2 specifically to maximize efficacy, and coined the short peptide "2019-nCoV-HR2P": Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein | Cellular & Molecular Immunology

They published the sequence in the first paper for EK1 but scrambled it, and I'm not a ninja at GROMACS. Couldn't one order some from a peptide synthesis service? I'm not sure how an amateur could synthesize peptides, I'm not familiar.

I wonder if there is a chemical that can inhibit the spike protein similarly, on a different section even. On that note my local U.S. uni is offering fee-for-service in-vitro compound testing on SARS-CoV-2.

A modeling of the spike proteins of many human coronaviruses: Prefusion structure of a human coronavirus spike protein

A modeling of the spike SARS-CoV-2 spike protein, and modeling of a common ancestor indicates it likely came from a bat: Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission | SpringerLink

[Edited on 22-3-2020 by andy1988]

andy1988 - 24-3-2020 at 22:43

ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. A possible explanation for the severe lung complications being seen in some people diagnosed with COVID-19. Perhaps they could substantially lower the death rate in older people with drug substitution (by restoring the "normal" amount of ACE2 receptors)?

Wuhan study shows lying face down improves breathing in severe COVID-19.

Here is the amino acid sequence for the 2019-nCoV-HR2P peptide. Solid phase peptide synthesis looks interesting.

Morgan - 29-3-2020 at 06:14

Quote: Originally posted by andy1988  
ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. A possible explanation for the severe lung complications being seen in some people diagnosed with COVID-19. Perhaps they could substantially lower the death rate in older people with drug substitution (by restoring the "normal" amount of ACE2 receptors)?

Wuhan study shows lying face down improves breathing in severe COVID-19.

Here is the amino acid sequence for the 2019-nCoV-HR2P peptide. Solid phase peptide synthesis looks interesting.


Saw this related tidbit this morning.
"A little translation: the virus has a spike protein that binds to an enzyme on the surfaces of cells, called angiotensin converting enzyme, or ACE. This enzyme is important in regulating blood pressure, and is expressed by cells in lung capillaries (fun fact: your lungs play an endocrine role in sending out signals that maintain blood pressure). This is one reason the virus has such a dangerous respiratory effect — the lungs are the primary targets, where it can use the spike protein to bind to cells that express ACE and drill into them."
https://freethoughtblogs.com/pharyngula/2020/03/28/where-did...

wg48temp9 - 29-3-2020 at 10:51

Quote: Originally posted by Morgan  
Quote: Originally posted by andy1988  
ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. A possible explanation for the severe lung complications being seen in some people diagnosed with COVID-19. Perhaps they could substantially lower the death rate in older people with drug substitution (by restoring the "normal" amount of ACE2 receptors)?

Wuhan study shows lying face down improves breathing in severe COVID-19.

Here is the amino acid sequence for the 2019-nCoV-HR2P peptide. Solid phase peptide synthesis looks interesting.


Saw this related tidbit this morning.
"A little translation: the virus has a spike protein that binds to an enzyme on the surfaces of cells, called angiotensin converting enzyme, or ACE. This enzyme is important in regulating blood pressure, and is expressed by cells in lung capillaries (fun fact: your lungs play an endocrine role in sending out signals that maintain blood pressure). This is one reason the virus has such a dangerous respiratory effect — the lungs are the primary targets, where it can use the spike protein to bind to cells that express ACE and drill into them."
https://freethoughtblogs.com/pharyngula/2020/03/28/where-did...


If the ACE inhibitor binds to ACE perhaps that interferes with the binding of the spike protein. I hope it does as I take an ACE inhibitor to reduce my blood pressure.

Morgan - 29-3-2020 at 11:35

Quote: Originally posted by wg48temp9  
Quote: Originally posted by Morgan  
Quote: Originally posted by andy1988  
ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. A possible explanation for the severe lung complications being seen in some people diagnosed with COVID-19. Perhaps they could substantially lower the death rate in older people with drug substitution (by restoring the "normal" amount of ACE2 receptors)?

Wuhan study shows lying face down improves breathing in severe COVID-19.

Here is the amino acid sequence for the 2019-nCoV-HR2P peptide. Solid phase peptide synthesis looks interesting.


Saw this related tidbit this morning.
"A little translation: the virus has a spike protein that binds to an enzyme on the surfaces of cells, called angiotensin converting enzyme, or ACE. This enzyme is important in regulating blood pressure, and is expressed by cells in lung capillaries (fun fact: your lungs play an endocrine role in sending out signals that maintain blood pressure). This is one reason the virus has such a dangerous respiratory effect — the lungs are the primary targets, where it can use the spike protein to bind to cells that express ACE and drill into them."
https://freethoughtblogs.com/pharyngula/2020/03/28/where-did...


If the ACE inhibitor binds to ACE perhaps that interferes with the binding of the spike protein. I hope it does as I take an ACE inhibitor to reduce my blood pressure.


"Research in experimental models has shown an increase in the number of ACE2 receptors in the cardiopulmonary circulation after intravenous infusions of ACE inhibitors."

"Since patients treated with ACEIs and ARBS will have increased numbers of ACE2 receptors in their lungs for coronavirus S proteins to bind to, they may be at increased risk of severe disease outcomes due to SARS-CoV-2infections," explains Diaz.
https://medicalxpress.com/news/2020-03-ace-inhibitors-angiot...

I have no idea if the above hypothesis is a certainty or not.

[Edited on 29-3-2020 by Morgan]

Morgan - 30-3-2020 at 08:41

There was an Interesting story today on TV of a younger person perhaps in their 20s saying the person was sitting up looking at his iPad even with very low oxygen levels. Then hours later dead. The account said it wasn't a gasping for air type of event but rather some young people are dying, it was recounted, as if a high altitude sickness,, falling asleep and not waking up.

Stay At Home orders

MadHatter - 1-4-2020 at 08:34

I take ACE inhibitors for my hypertension and have
early stages of emphysema. This puts me at high
risk for the virus. Here in Maine, we go into a home
quarantine starting tomorrow(APRIL 2) to continue
for 4 weeks. We're allowed outside our homes only
for essentials(work, food, medical). Good luck to
everybody.

Mush - 1-4-2020 at 15:37

Favipiravir
https://en.wikipedia.org/wiki/Favipiravir

In February 2020, Favipiravir was being studied in China for experimental treatment of the emergent COVID-19 (novel coronavirus disease).[7][8] On 17 March 2020, Chinese officials suggested the drug had been effective in treating COVID in Wuhan and Shenzhen.[9][10]

On 22 March 2020 Italy has approved the drug for experimental use against COVID-19 and has begun conducting trials in 3 regions most affected by the disease.[22] The Italian Pharmaceutical Agency, however, has reminded the public that the existing evidence in support of this drug is scant and preliminary.[23]

On 17 March 2020, Chinese officials suggested that Favipiravir seemed to be effective in treating COVID-19 in Wuhan and Shenzhen.[33][34][35]

A study on 80 patients comparing it to lopinavir/ritonavir found that it significantly reduced viral clearance time to 4 days, compared to 11 days for the control group, and that 91.43% of patients had improved CT scans with few side effects. The limitation of this study is that it was not a randomized double-blinded placebo-controlled clinical trial.[36][37]



The complete synthesis of favipiravir from 2-aminopyrazine
Abstract

Favipiravir was first synthesized from an inexpensive and commercially available starting material, 2-aminopyrazine. The preferred route embedded within Scheme 4 consisted of seven steps, and was highlighted by the novel and efficient synthesis of 3,6-dichloropyrazine-2-carbonitrile 8. This intermediate was prepared in four successive steps which were regioselective chlorination of the pyrazine ring, bromination, Pd-catalyzed cyanation, and Sandmeyer diazotization/chlorination. This protocol eliminated the hazardous POCl3 of previous synthetic methods and offered a better yield (48%) which was 1.3-fold higher than a recently published procedure. From intermediate 8, the subsequent nucleophilic fluorination, nitrile hydration and hydroxyl substitution efficiently afforded the target product. Another synthetic approach with the same starting material was also investigated to bypass the allergy-causing dichloro intermediate 8. However, the key step of monofluorination at the pyrazine C6 position of intermediate 19 or 22 was not achieved.

http://hostuje.net/file.php?id=3567994be102b15b282e1ae757e8f...
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Synthesis of [18F]Favipiravir and Biodistribution in C3H/HeN Mice as Assessed by Positron Emission Tomography
https://www.nature.com/articles/s41598-018-37866-z

[Edited on 1-4-2020 by Mush]

kencbk - 2-4-2020 at 04:15

Guys check this out
https://youtu.be/vE4_LsftNKM
according to this source.
Zinc ionophore found in quercetin may help prevent viral reproduction, Quercetin is a zinc ionophore it helps zinc enter the cells, zinc ions disrupts the RNA replication of the SARS-CoV-2

is there more research into this?

just an input, Stay safe everyone

Morgan - 2-4-2020 at 07:42

I saw a Dr. Gallo on MSNBC with Brian Williams last night who said the virus had mutatedi n Italy and that there are variants identified in the US. He also stated that he felt almost certain there was something already that will work and that he would announce it the next time he's on air.

Dr. Robert Gallo Featured on MSNBC’s 11th Hour with Brian Williams
https://youtube.com/watch?v=E9z-E1FG0Gg
https://en.wikipedia.org/wiki/Robert_Gallo

But who knows what side effects or if the supposed cure really holds a promise.

[Edited on 2-4-2020 by Morgan]

Morgan - 2-4-2020 at 17:03

As an aside ...
My Florida governor Ron DeSantis just doesn't get it. Prevention is out the window.
https://freethoughtblogs.com/pharyngula/2020/04/02/jesus-is-...

[Edited on 3-4-2020 by Morgan]

solo - 2-4-2020 at 17:28

...informative reading...solo

https://connect.biorxiv.org/relate/content/181





[Edited on 3-4-2020 by solo]

Morgan - 4-4-2020 at 06:35

I wonder if they are giving people too many drugs? Aside from being sedated, he was on antibiotics and 1 and possibly 2 experimental drugs, and 3 blood pressure medications. I'm guessing perhaps Tylenol for fever too.Tough to watch without getting watery eyes.

Widow describes emotional moment she lost her husband to Covid-19
https://youtube.com/watch?v=wmqvYiTZerk

[Edited on 4-4-2020 by Morgan]

jamit - 5-4-2020 at 22:58

Quote: Originally posted by Morgan  
As an aside ...
My Florida governor Ron DeSantis just doesn't get it. Prevention is out the window.
https://freethoughtblogs.com/pharyngula/2020/04/02/jesus-is-...

[Edited on 3-4-2020 by Morgan]


Morgan, your post has nothing to do with science except to attack religious people. Do you think all religious people are like that. 99% of Christians and churches obey their governing leaders.

I assume you are not religious... I highly doubt anyone with any sense of fairness would have posted that to make “fun” of Christian evangelicals. Should I assume that all atheists and secular people like yourself are arrogance and that their “religion” is not true science but “secular science”.

Brian William and msnbc is utter garbage. They spread misinformation particularly about religious people and they divide Americans in times like this when they should help bring together Americans! I’m sorry but your post offends me. Let’s keep to the science and don’t bring politics and religion into the mix. Otherwise start a new post like “ religion and covid19”.

Pyro_cat - 18-4-2020 at 01:26

I just resent the people who keep close talking wont wear masks and make no effort.

I went through a phase where I quit wearing shoes and would get shit for being in stores barefoot.

You dont have any shoes !!!! Mythical Heath codes and insurance regulations !!! You cant be in here !

Meanwhile no face-mask during a pandemic and no confrontation ?

If people were 1/10th afraid of covid 19 as they were of athletes foot or me stepping on some glass this pandemic would be over in two weeks.

Real science is easy. Social science makes no sense at all.

Morgan - 18-4-2020 at 16:44

Quote: Originally posted by jamit  
Quote: Originally posted by Morgan  
As an aside ...
My Florida governor Ron DeSantis just doesn't get it. Prevention is out the window.
https://freethoughtblogs.com/pharyngula/2020/04/02/jesus-is-...

[Edited on 3-4-2020 by Morgan]


Morgan, your post has nothing to do with science except to attack religious people. Do you think all religious people are like that. 99% of Christians and churches obey their governing leaders.

I assume you are not religious... I highly doubt anyone with any sense of fairness would have posted that to make “fun” of Christian evangelicals. Should I assume that all atheists and secular people like yourself are arrogance and that their “religion” is not true science but “secular science”.

Brian William and msnbc is utter garbage. They spread misinformation particularly about religious people and they divide Americans in times like this when they should help bring together Americans! I’m sorry but your post offends me. Let’s keep to the science and don’t bring politics and religion into the mix. Otherwise start a new post like “ religion and covid19”.


By all means let's bring Americans together.

"On Friday, Trump said that he would attend Easter services on Sunday, virtually, along with congregants of Dallas’ First Baptist. I’m going to be watching Pastor Robert Jeffress,” Trump said at his daily coronavirus task force briefing. "He’s been a great guy, and I’m going to be watching on a laptop."

Robert James Jeffress Jr. (born November 29, 1955) is an American Southern Baptist (Evangelical) pastor, author, and radio and television host. He is the Senior Minister of the 14,000-member[2] First Baptist Church in Dallas, Texas[3] and is a Fox News Contributor.[4] His sermons are broadcast on the television and radio program Pathway to Victory, which is broadcast on more than 1,200 television stations in the United States and 28 other countries, and is heard on 900 stations and broadcast live in 195 countries.[5][6]

Jeffress believes that the teachings of Judaism, Islam, Mormonism, and Hinduism reject "the truth of Christ", and that their adherents will go to hell if they do not accept Christ.[26][27] Also in 2010, Jeffress referred to Roman Catholicism as a "Satanic" result of "Babylonian mystery religion".[30] In another interview the same year, he said, "Mormonism is wrong, it is a heresy from the pit of Hell; Judaism, you can't be saved being a Jew, you know who said that by the way, the three greatest Jews in the New Testament, Peter, Paul, and Jesus Christ, they all said Judaism won't do it, it's faith in Jesus Christ."[31] In October 2011, at the Values Voter Summit, Jeffress called The Church of Jesus Christ of Latter-day Saints (LDS Church) "a cult." He received widespread criticism for the statement but did not retract it despite Mitt Romney's request for him to do so.[32]
Wiki