Newly-Synthesized Peptide Could Disarm SARS-CoV-2 Coronavirus

Sci-news ^ | 2020 March 31 | News staff

[CutePuppy]

Chemists at the Massachusetts Institute of Technology (MIT) have chemically synthesized a new peptide (a short protein fragment) that can bind to part of SARS-CoV-2's spike protein, a key protein responsible for getting the virus into mammalian cells, potentially disarming it.

"We have a lead compound that we really want to explore, because it does, in fact, interact with a viral protein in the way that we predicted it to interact, so it has a chance of inhibiting viral entry into a host cell," said senior author Dr. Brad Pentelute, a researcher in the Department of Chemistry at MIT.

Coronaviruses, including SARS-CoV-2, have many protein spikes protruding from their viral envelope.

A specific region of SARS-CoV-2's spike protein, known as the receptor binding domain, binds to a receptor called angiotensin-converting enzyme 2 (ACE2). This receptor is found on the surface of many human cells, including those in the lungs.

In hopes of developing drugs that could block viral entry, Dr. Pentelute and colleagues performed computational simulations of the interactions between the ACE2 receptor and the receptor binding domain of SARS-CoV-2's spike protein. ..... < snip >

..... "This kind of simulation can give us views of how atoms and biomolecules interact with each other, and which parts are essential for this interaction," said first author Dr. Genwei Zhang, a postdoctoral researcher in the Department of Chemistry at MIT. ..... < snip >

The scientists then used peptide synthesis technology to rapidly generate a 23-amino acid peptide with the same sequence as the alpha helix of the ACE2 receptor. ..... < snip >

They found that the longer peptide showed strong binding to the receptor binding domain of SARS-CoV-2. ..... < snip >

[CutePuppy]

Most people are familiar with ACE inhibitors used in treating heart conditions, such as hypertension. was identified as a receptor for both SARS-CoV and NL63.

If this is successful, it could mean more than just a treatment, it could mean prevention of COVID-19 and possibly fast development against future novel coronaviruses, along with immunity-boosting approaches such as intake of absorbable forms of zinc, vitamins D3, B-complex, etc.

[Dark Knight]

It is just a bandage. An ACE bandage.

DK

[Paladin2]

Lead?

I’d use spent Uranium...

Or maybe Wolfram.

[Paladin2]

Do they make Copper jacketed lead based mini proteins?

[TChad]

We have a lead compound...

Lead as in Pb or as in leads the pack?

[CutePuppy]

MIT also has been developing an open-source ventilator designs that it hopes could help as the escalating pandemic strains supplies of the machines.

From Can low-cost, open-source ventilator designs help save lives? - by James Temple, 2020 March 24

MIT researchers hope to publish open-source designs for a low-cost respirator that could potentially help Covid-19 patients struggling with critical respiratory problems.

The motorized device automatically compresses widely available bag valve masks, the sort of manual resuscitator used by ambulance crews to assist patients with breathing problems. The designs could arrive as a growing number of engineers, medical students, and hobbyists attempt to build or share specifications for makeshift respirators — of unknown quality and safety — amid rising fears of widespread shortages as the coronavirus epidemic escalates.

The team recently launched a website unveiling the MIT Emergency Ventilator Project, or E-Vent, which now states the device "is being submitted" to the Food and Drug Administration for rapid review under an "Emergency Use Authorization." Last week, MIT Technology Review was informed the team intended to test the devices on pigs in recent days, though it's still unclear what the results were. ..... < snip >

..... It's also not clear if the team has yet fully answered the fundamental question of the project: Is it possible to safely ventilate a Covid-19 patient by automatically actuating a manual resuscitator?

If that answer is yes, the hope is that openly publishing the designs, test results, and related medical information could enable those with the necessary manufacturing capacity and expertise to produce reliable, safe, and affordable respirators. Even so, the site stresses the device should be operated only under the supervision of trained medical professionals and is not a replacement for an FDA-approved intensive care unit ventilator "in terms of functionality, flexibility, and clinical efficacy." ..... < snip >

..... Researchers at the University of Minnesota are developing a similar device, which also relies on automating the pumping of "ambu" bags. They also hope to soon publish open-source designs. ..... < snip >

[rfp1234]

WTH? Lead (Pb?) mentioned here, and an earlier article said antiviral drugs could be made by a tobacco company.

Now all we need to drive environmentalists even crazier, is a study showing that asbestos fibers can be wrapped around the viruses to neutralize them. [\s].

[exDemMom]

It leads the pack.

[CutePuppy]

We have a lead compound... Lead as in Pb or as in leads the pack?

The latter. They rapidly prototyped many different compounds of different length, starting with only 12 amino, and then tested against 23 amino acids chain, to measure how strongly two molecules bind together. They found longer chains to be stronger bound to ACE2 receptors of CoV-2.

Their benchtop flow-based peptide synthesis machine can form linkages between amino acids in about 37 seconds, and it takes less than an hour to generate complete peptide molecules containing up to 50 amino acids.

[allendale]

Much has been speculated about the ACE receptors that seem to be the portal of entry for this virus. There is the question if the use of ACE inhibitors such as Vasotec or ARBs such as valsartan either alter those ACE receptors and inhibit virus infectivity or do they increase the number of ACE sites an make infection more likely.
By now the CDC should have collected enough data on this issue to advise the public.

[familyop]

"Dry land is not just our destination, it is our destiny!" --Deacon, in the movie, "Waterworld"

[libh8er]

I read an article that warned hypertensive patients on ACE inhibitors NOT to get off their medication in case they suspect Corona infection.

[TChad]

It leads the pack.

Thanks.

[TChad]

Wow. Big fun.

[Bommer]

Get in line! 18 months for testing, and half the country infected ot dead!

[gasport]

Do you have a reference?

[libh8er]

I don’t right now but it was in my Google news feed. You could try Googling ‘ACE inhibitors Covid ‘. Heck, I think I will go do that myself.

[libh8er]

https://www.medscape.com/viewarticle/927952

You will need to register (free) to read that

[CutePuppy]

I doubt current crop of ARBs (sartans) would do any good on ACE2.

The AACs used on CoV-2’s receptors seem to have been effective on previous generations of CoV (NL63, HKU1 etc.) so there is a good chance this is a real deal, and not just against COVID19.

[grey_whiskers]

The spike protein has a cleavage site which reacts with furin-related enzymes on the cell to increase infectivity 1,000-fold compared to the ACE receptor interaction...do these peptides interfere with that?

Secondly, will this compound need to be taken prophylactically forever?
What I’m thinking, is if the compound interferes with the virus binding to cells, will the body develop enough of an immune response, to maintain immunity? Compare the common cold (also a coronavirus) which keeps circling around year after year.