Connect with us

Published

on

By Pooja Toshniwal Paharia Sep 5 2023

In a recent study posted to the bioRxiv preprint* server, researchers in Sweden investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein amyloid as a potential triggering factor for protein misfolding and amyloid formation in neurodegenerative diseases (NDs).

Neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD) are accelerated by the conversion of human proteins into misfolded amyloid fibril aggregates. This process is self-perpetuating through seeding from preformed fibril seeds. SARS-CoV-2 S, abundant in the inflammatory response, is a plausible mechanism for amyloid fibril formation.

Study: SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide. Image Credit: Design_Cells / Shutterstock

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information. About the study

In the present study, researchers performed cross-seeding neurodegenerative disease-related proteins with S protein amyloid fibrils.

In the in vitro environment, seeding studies were carried out by cross-seeding human prion protein (HuPrP)- and the Aβ1-42 protein-derived with seven distinct amyloid protein fibrils obtained from SARS-CoV-2 S peptides. The researchers examined whether SARS-CoV-2 S protein-derived amyloid protein accelerates the human A peptide and HuPrP fibril formation. Thus, prefabricated fibrils from seven SARS-CoV-2 Wuhan-Hu-1 strain S amyloidogenic sequences (spike seeds)-derived peptides, each 20 amino-acid long, were added, matching the starting protein sequence of the S glycoprotein.

E. Coli was used to make human PrP. To test seeding effect specificity, 10% seed concentrations of different amyloidogenic proteins such as Aβ1-42, TTR, insulin, and lysozyme were introduced. ThT fluorescence changes with time were used to monitor fibrillation. To slow the fibrillation rate of the unseeded HuPrP reaction and dissolve the S protein peptides, hexafluoro-isopropanol (HFIP) was used. The heterologous seed might be a protein that differs from the substrate by a single point mutation, the same protein from a different species, or another protein related to the same illness.

The seeding effect of S protein amyloids was studied using Aβ1-42 as a substrate. Replicate reaction samples were obtained for inspection using transmission electron microscopy (TEM) while ThT was monitoring Aβ1-42 fibril development. To match the greatest concentration of S protein peptide amyloids, the team added control seeds to HuPrP at 0.010 mg/mL concentration. The positive control was the fibrillar form of HuPrP90-231 at 0.0010 mg/mL concentration. Results

Using an in vitro conversion experiment, the researchers discovered that S protein-amyloid fibril-seeded amyloid production of CJD-associated HuPrP was significantly accelerated. The HuPrP conversion assay was seeded with different in vitro-generated disease-associated amyloid fibrils, and the Aβ1-42 protein was exposed to a panel of control seeds, but no fibril development was accelerated for insulin, lysozyme, or TTR. The findings indicated seeding as a unique property of S protein-amyloid fibrils rather than a universal impact.

Positive controls included Aβ1-42 protein fibrils and an amalgamation of seven fibrillated S glycoprotein peptides, and both controls indicated seeding action. Further, S protein-amyloid fibril seeds enhanced amyloid fibril development in AD-associated Aβ1-42. Spike532 (532NLVKNKCVNFNFNGLTGTGV551) was most successful in seeding HuPrP, whereas Spike601 (601GTNTSNQVAVLYQDVNCTEV620) was most effective in seeding Aβ1-42, demonstrating substrate-dependent selectivity of the cross-seeding activity.

The development of Aβ1-42 fibrils was enhanced by all seven S protein amyloids. However, like with HuPrP seeding, there was a considerable differential in seeding efficiency across the various S protein amyloids, with Aβ1-42 being more responsive to Spike601. The exponential phase of growth was finished for all seeded samples at 120 minutes in the TEM study, whereas the unseeded specimen, lacking fibrillar components but rich in oligomeric structures, continued to be in the beginning nucleation phase. Amyloid fibrils were seen in all S peptide amyloid-seeded samples.

The CJD-linked HuPrP and AD-linked Aβ1-42 peptides showed cross-seeding vulnerability with SARSCoV-2 S glycoprotein amyloids. Spike532 amyloid considerably shortened the lag period of amyloid production for HuPrP by a greater extent than other amyloid peptides, but Spike192 amyloid protein did not significantly reduce the lag period.

Spike532 seeding significantly reduced the lag period of HuPrP protein fibrillation by 80%, from 712 to 135 minutes on average. The 10-fold spike seed dilution nearly eliminated the seeding abilities of the S protein amyloids. Nevertheless, Spike532 amyloid almost retained its ability to reduce the lag period, with only a 10% reduction in the ability by the dilution.

The 0.010 mg/mL SARS-CoV-2 S protein mixture reduced lag duration from 6.75 hours to 5.1 hours (25%). Insulin fibrils reduced the lag period of HuPrP protein fibrillation considerably, while TTR, lysozyme, and the Aβ1-42 protein fibrils did not. The authors did not propose a mechanistic explanation for the lower Aβ1-42/40 ratio among SARS-CoV-2-positive individuals, but Aβ1-42 accumulation might be one. All seven investigated SARS-CoV-2 S peptide amyloids significantly reduced the duration of fibril generation, especially in an already swift, unseeded response. Spike532 was the most efficient at HuPrP seeding, while Spike601 was the most efficient for Aβ1-42 seeding.

Overall, the study findings showed that SARS-CoV-2 S glycoprotein amyloid fibrils preferentially and specifically enhanced the production of HuPrP and amyloid peptide amyloid fibrils. The findings, albeit solely in vitro, indicated that S protein-amyloid fibril cross-seeding may be involved in the growing number of cases of CJD, AD, and perhaps other NDs in the aftermath of COVID-19.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information. Journal reference: Preliminary scientific report. Johan Larsson, Ebba Hellstrand, Per Hammarström, Sofie Nyström. SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide. bioRxiv preprint 2023, DOI: https://doi.org/10.1101/2023.09.01.555834, https://www.biorxiv.org/content/10.1101/2023.09.01.555834v1

Continue Reading

Business

Sir Keir Starmer pledges to protect UK companies from Trump tariff ‘storm’

Published

on

By

Sir Keir Starmer pledges to protect UK companies from Trump tariff 'storm'

Sir Keir Starmer has said his government stands ready to use industrial policy to “shelter British business from the storm” after Donald Trump’s new 10% tariff kicked in.

The UK was among a number of countries hit with the lowest import duty rate following the president’s announcement on 2 April – which he called ‘Liberation Day’, while other nations, such as Vietnam, Cambodia and China face much higher US levies.

But a global trade war will hurt the UK’s open economy.

The prime minister said “these new times demand a new mentality”, after the 10% tax on British imports into America came into force on Saturday. A 25% US levy on all foreign car imports was introduced on Thursday.

It comes as Jaguar Land Rover announced it would “pause” shipments to the US for a month, as firms grapple with the new taxes.

On Saturday, the car manufacturer said it was working to “address the new trading terms” and was looking to “develop our mid to longer-term plans”.

Please use Chrome browser for a more accessible video player

Jobs fears as Jaguar halts shipments

Referring to the tariffs, Sir Keir said “the immediate priority is to keep calm and fight for the best deal”.

Writing in The Sunday Telegraph, he said that in the coming days “we will turbocharge plans that will improve our domestic competitiveness”, adding: “We stand ready to use industrial policy to help shelter British business from the storm.”

It is believed a number of announcements could be made soon as ministers look to encourage growth.

NI contribution rate for employers goes up

From Sunday, the rate of employer NICs (national insurance contributions) increased from 13.8% to 15%.

At the same time, firms will also pay more because the government lowered the salary threshold at which companies start paying NICs from £9,100 to £5,000.

Also, the FTSE 100 of leading UK companies had its worst day of trading since the start of the pandemic on Friday, with banks among some of the firms to suffer the sharpest losses.

Sir Keir said: “This week, the government will do everything necessary to protect Britain’s national interest. Because when global economic sands are shifting, our laser focus on delivering for Britain will not. And these new times demand a new mentality.”

Please use Chrome browser for a more accessible video player

Trump defiant despite markets

UK spared highest tariff rates

Some of the highest rates have been applied to “worst offender” countries including some in Southeast Asia. Imports from Cambodia will be subject to a 49% tariff, while those from Vietnam will face a 46% rate. Chinese goods will be hit with a 34% tariff.

Imports from France will have a 20% tariff, the rate which has been set for European Union nations. These will come into effect on 9 April.

Read more:
Red wall on Wall Street – but Trump undeterred
How will UK respond to Trump’s tariffs?

Sir Keir has been speaking to foreign leaders on the phone over the weekend, including French President Emmanuel Macron, Italian Prime Minister Giorgia Meloni and Australian Prime Minister Anthony Albanese, to discuss the tariff changes.

A Downing Street spokesperson said of the conversation between Sir Keir and Mr Macron: “They agreed that a trade war was in nobody’s interests but nothing should be off the table and that it was important to keep business updated on developments.

“The prime minister and president also shared their concerns about the global economic and security impact, particularly in Southeast Asia.”

👉 Follow Trump 100 on your podcast app 👈

Trump’s warning

Mr Trump has warned Americans the tariffs “won’t be easy”, but urged them to “hang tough”.

In a post on his Truth Social platform, he said: “We are bringing back jobs and businesses like never before.

“Already, more than FIVE TRILLION DOLLARS OF INVESTMENT, and rising fast!

“THIS IS AN ECONOMIC REVOLUTION, AND WE WILL WIN. HANG TOUGH, it won’t be easy, but the end result will be historic.”

Continue Reading

Politics

Sir Keir Starmer pledges to protect UK companies from Trump tariff ‘storm’

Published

on

By

Sir Keir Starmer pledges to protect UK companies from Trump tariff 'storm'

Sir Keir Starmer has said his government stands ready to use industrial policy to “shelter British business from the storm” after Donald Trump’s new 10% tariff kicked in.

The UK was among a number of countries hit with the lowest import duty rate following the president’s announcement on 2 April – which he called ‘Liberation Day’, while other nations, such as Vietnam, Cambodia and China face much higher US levies.

But a global trade war will hurt the UK’s open economy.

The prime minister said “these new times demand a new mentality”, after the 10% tax on British imports into America came into force on Saturday. A 25% US levy on all foreign car imports was introduced on Thursday.

It comes as Jaguar Land Rover announced it would “pause” shipments to the US for a month, as firms grapple with the new taxes.

On Saturday, the car manufacturer said it was working to “address the new trading terms” and was looking to “develop our mid to longer-term plans”.

Please use Chrome browser for a more accessible video player

Jobs fears as Jaguar halts shipments

Referring to the tariffs, Sir Keir said “the immediate priority is to keep calm and fight for the best deal”.

Writing in The Sunday Telegraph, he said that in the coming days “we will turbocharge plans that will improve our domestic competitiveness”, adding: “We stand ready to use industrial policy to help shelter British business from the storm.”

It is believed a number of announcements could be made soon as ministers look to encourage growth.

NI contribution rate for employers goes up

From Sunday, the rate of employer NICs (national insurance contributions) increased from 13.8% to 15%.

At the same time, firms will also pay more because the government lowered the salary threshold at which companies start paying NICs from £9,100 to £5,000.

Also, the FTSE 100 of leading UK companies had its worst day of trading since the start of the pandemic on Friday, with banks among some of the firms to suffer the sharpest losses.

Sir Keir said: “This week, the government will do everything necessary to protect Britain’s national interest. Because when global economic sands are shifting, our laser focus on delivering for Britain will not. And these new times demand a new mentality.”

Please use Chrome browser for a more accessible video player

Trump defiant despite markets

UK spared highest tariff rates

Some of the highest rates have been applied to “worst offender” countries including some in Southeast Asia. Imports from Cambodia will be subject to a 49% tariff, while those from Vietnam will face a 46% rate. Chinese goods will be hit with a 34% tariff.

Imports from France will have a 20% tariff, the rate which has been set for European Union nations. These will come into effect on 9 April.

Read more:
Red wall on Wall Street – but Trump undeterred
How will UK respond to Trump’s tariffs?

Sir Keir has been speaking to foreign leaders on the phone over the weekend, including French President Emmanuel Macron, Italian Prime Minister Giorgia Meloni and Australian Prime Minister Anthony Albanese, to discuss the tariff changes.

A Downing Street spokesperson said of the conversation between Sir Keir and Mr Macron: “They agreed that a trade war was in nobody’s interests but nothing should be off the table and that it was important to keep business updated on developments.

“The prime minister and president also shared their concerns about the global economic and security impact, particularly in Southeast Asia.”

👉 Follow Trump 100 on your podcast app 👈

Trump’s warning

Mr Trump has warned Americans the tariffs “won’t be easy”, but urged them to “hang tough”.

In a post on his Truth Social platform, he said: “We are bringing back jobs and businesses like never before.

“Already, more than FIVE TRILLION DOLLARS OF INVESTMENT, and rising fast!

“THIS IS AN ECONOMIC REVOLUTION, AND WE WILL WIN. HANG TOUGH, it won’t be easy, but the end result will be historic.”

Continue Reading

World

IDF says it mistakenly identified Gaza aid workers as threat – after video of deadly attack emerges

Published

on

By

IDF says it mistakenly identified Gaza aid workers as threat - after video of deadly attack emerges

The IDF says it mistakenly identified a convoy of aid workers as a threat – following the emergence of a video which proved their ambulances were clearly marked when Israeli troops opened fire on them.

The bodies of 15 aid workers – including eight medics working for the Palestine Red Crescent Society (PRCS) – were found in a “mass grave” after the incident, according to the head of the UN Office for Coordination of Humanitarian Affairs Jonathan Whittall.

The Israeli military originally claimed an investigation found the vehicles did not have any headlights or emergency signals and were therefore targeted as they looked “suspicious”.

But video footage obtained by the PRCS, and verified by Sky News, showed the ambulances and a fire vehicle clearly marked with flashing red lights.

In a briefing from the IDF, it said the ambulances arrived in the Tel Sultan neighbourhood in Rafah shortly after a Hamas police vehicle drove through.

Palestinians mourn medics, who came under Israeli fire while on a rescue mission, after their bodies were recovered, according to the Red Crescent, at Nasser hospital in Khan Younis in the southern Gaza Strip March 31, 2025. REUTERS/Hatem Khaled/File Photo
Image:
Palestinians mourning the medics after their bodies were recovered. Pic: Reuters

An IDF surveillance aircraft was watching the movement of the ambulances and notified troops on the ground. The IDF said it will not be releasing that footage.

When the ambulances arrived, the soldiers opened fire, thinking the medics were a threat, according to the IDF.

The soldiers were surprised by the convoy stopping on the road and several people getting out quickly and running, the IDF claimed, adding the soldiers were unaware the suspects were in fact unarmed medics.

An Israeli military official would not say how far away troops were when they fired on the vehicles.

The IDF acknowledged that its statement claiming that the ambulances had their lights off was incorrect, and was based on the testimony from the soldiers in the incident.

The newly emerged video footage showed that the ambulances were clearly identifiable and had their lights on, the IDF said.

The IDF added that there will be a re-investigation to look into this discrepancy.

Analysis: Video undermines Israel’s account of aid worker deaths

The clip is filmed through a vehicle windscreen - with three red light vehicles visible in front
Image:
The clip is filmed through a vehicle windscreen – with three red light vehicles visible in front

Addressing the fact the aid workers’ bodies were buried in a mass grave, the IDF said in its briefing this is an approved and regular practice to prevent wild dogs and other animals from eating the corpses.

The IDF could not explain why the ambulances were also buried.

The IDF said six of the 15 people killed were linked to Hamas, but revealed no detail to support the claim.

Please use Chrome browser for a more accessible video player

Bodies of aid workers found in Gaza

The newly emerged footage of the incident was discovered on a phone belonging to one of the workers who was killed, PRCS president Dr Younis Al Khatib said.

“His phone was found with his body and he recorded the whole event,” he said. “His last words before being shot, ‘Forgive me, mom. I just wanted to help people. I wanted to save lives’.”

Sky News used an aftermath video and satellite imagery to verify the location and timing of the newly emerged footage of the incident.

More from Sky News:
Israeli troops expand Gaza ‘security zone’
What happened to the ceasefire?

Please use Chrome browser for a more accessible video player

Aid worker attacks increasing

It was filmed on 23 March north of Rafah and shows a convoy of marked ambulances and a fire-fighting vehicle travelling south along a road towards the city centre. All the vehicles visible in the convoy have their flashing lights on.

The footage was filmed early in the morning, with a satellite image seen by Sky News taken at 9.48am local time on the same day showing a group of vehicles bunched together off the road.

Continue Reading

Trending