Wuhan Corona Virus / COVID-19 / SARS-CoV-2

[JimF]

The proteins they engineer are very specific to their purpose. That is the advantage of computer modeling. They can try out millions to get the specific one that matches the target the best.
The chances of affecting other cells and producing side effects is much smaller than before. That is the same advantage as Folding, only via different means.

[Jonazz]

The proteins they engineer are very specific to their purpose. That is the advantage of computer modeling. They can try out millions to get the specific one that matches the target the best.
The chances of affecting other cells and producing side effects is much smaller than before. That is the same advantage as Folding, only via different means.

Both F@H and R@H are amazing projects. I'm glad to have contributed to both.

[robertmiles]

A scientific paper showing that many viruses use glycans for shielding from the immune system:

https://www.biorxiv.org/content/10.1101 ... 1.full.pdf

See Figure 6.

This appears to show that the glycans shielding the viruses are built from mannose.

Does this make the various protein sites where the glycans bind a good target for binding something to block glycan attachment?

[robertmiles]

Human metabolism can turn glucose into mannose; therefore diet is not the only source of mannose except in some people with genetic disorders blocking this conversion.

Human metabolism uses mannose for various purpose, so permanently eliminating it is not a good idea.

It is normally NOT used as an energy source.

Too high a level of mannose can be fatal.

High levels of mannose are often seen in those with diabetes; this MIGHT be why COVID-19 is often more severe in those with diabetes.

MANNOSE METABOLISM: MORE THAN MEETS THE EYE

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252654/

The places where proteins or glycans connect to cell walls are called GPI anchors.

Glycosylphosphatidylinositol (GPI) Anchors: Biochemistry and Cell Biology: Introduction to a Thematic Review Series

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689333/

Human metabolism uses some on human cell walls, so elimination all of them is not a good idea.

A GPI anchor contains mannose and a phospholipid.

[robertmiles]

The SARS-CoV2 virus which causes COVID-19 DOES use glycans, built mostly from mannose, for shielding from the immune system.

Site-specific glycan analysis of the SARS-CoV-2 spike

https://science.sciencemag.org/content/ ... ce.abb9983

Some of these glycans are hijacked from the ones human cells normally use from various purposes.

[robertmiles]

World's dominant strain of coronavirus 'is 10 TIMES more infectious than the one that jumped to humans in China' because it mutated so its vital spike protein doesn't snap as often in the body, scientists say

https://www.msn.com/en-us/health/medica ... 7l?ocid=se

[Simplex0]

In the post on the News page from March 15 https://foldingathome.org/2020/03/15/co ... ple-terms/ they says that....

"We’re simulating the dynamics of COVID-19 proteins to hunt for new therapeutic opportunities."

But COVID-19 is the disease caused by the new coronavirus SARS-CoV-2.
Should I take this as that they are referring to proteins in the coronavirus SARS-CoV-2 or is there also other proteins related to the COVID-19 disease that they are referring to here?

Tomas

[JohnChodera]

Tomas,

Both viral (SARS-CoV-2) and human host proteins that are essential to virus replication are of interest, since therapeutics targeted at either could potentially be effective in treating COVID-19 disease.

Folding@home as worked to set up this website with the Molecular Sciences Software Institute (MolSSI) to share structural, simulation, and compound data to accelerate COVID-19 drug discovery (including all data from Folding@home as it gets rapidly posted):
http://covid.molssi.org/

It's more targeted toward scientists, but gives an index of the various proteins (viral and host) that folks have been interested in targeting.

Finally, this is only for viral proteins, but Carl Zimmer's beautiful NYTimes piece is definitely worth a look:
https://www.nytimes.com/interactive/202 ... otein.html

There's also this really cool recent paper from UCSF that reveals a large number of other more speculative host protein targets that could be potential targets for therapeutics:
https://www.nature.com/articles/s41586-020-2286-9

[Simplex0]

Thank you JohnChodera

[robertmiles]

Supercomputer-Powered Research Uncovers Signs of ‘Bradykinin Storm’ That May Explain COVID-19 Symptoms

https://www.hpcwire.com/2020/07/28/supe ... -symptoms/


In Big Win for COVID-19 Research, Neocortix Brings Arm Support to Folding@home, Rosetta@home

https://www.hpcwire.com/2020/07/28/in-b ... settahome/


Structural analysis of COVID-19 spike protein provides insight into its evolution

https://www.sciencedaily.com/releases/2 ... 105122.htm


In cell studies, seaweed extract outperforms remdesivir in blocking COVID-19 virus

https://www.sciencedaily.com/releases/2 ... 104228.htm

[robertmiles]

The Bradykinin Hypothesis may explain Covid 19's diverse symptoms

https://www.dailykos.com/stories/2020/9 ... n=trending

[Jonazz]

A new paper from the guys at Rosetta@Home:

https://science.sciencemag.org/content/ ... ce.abd9909

They developed antibodies to fights the virus.

[gunnarre]

Covid Moonshot begins animal testing:

Dear Moonshot Community,

After 9 months of work from over 500 scientists and 24 global organisations, the Moonshot team is now beginning animal testing of our most promising compounds.

We have already demonstrated the ability to protect mammalian cells against being killed by the SARS-CoV-2 virus; a significant step in moving towards actual antivirals. Please take a read of what's been happening recently, what's planned, and how you can help.

Current Pipeline of Experiments

What tests have we done so far?

• Tested 9 compounds to establish their metabolic profile and other important 'ADMET' properties.

What tests are ongoing?

• 40 compounds are being tested for other key properties such as clearance, hydrophobicity, and human plasma protein binding.

What tests are planned?

• Further ADME tests, including more detailed analysis of characteristics such as absorption, interaction with liver enzymes, and impact on cardiac function.
• Pharmacokinetic testing in rats.
• Finding the correct dosage.
• Efficacy of the compound in curing hamsters infected with COVID.
• Toxicity experiments in rats and other animal species.

(...)

[foldy]

Is this a vaccine or a therapy?

[gunnarre]

It is a therapy, not a vaccine.