Salk Institute for Biological Studies

The novel coronavirus' spike protein plays additional key role in illness

Salk researchers and collaborators show how the protein damages cells, confirming COVID-19 as a primarily vascular disease

Newswise — LA JOLLA--(April 30, 2021) Scientists have known for a while that SARS-CoV-2's distinctive "spike" proteins help the virus infect its host by latching on to healthy cells. Now, a major new study shows that they also play a key role in the disease itself.

The paper, published on April 30, 2021, in Circulation Research, also shows conclusively that COVID-19 is a vascular disease, demonstrating exactly how the SARS-CoV-2 virus damages and attacks the vascular system on a cellular level. The findings help explain COVID-19's wide variety of seemingly unconnected complications, and could open the door for new research into more effective therapies.

"A lot of people think of it as a respiratory disease, but it's really a vascular disease," says Assistant Research Professor Uri Manor, who is co-senior author of the study. "That could explain why some people have strokes, and why some people have issues in other parts of the body. The commonality between them is that they all have vascular underpinnings."

Salk researchers collaborated with scientists at the University of California San Diego on the paper, including co-first author Jiao Zhang and co-senior author John Shyy, among others.

While the findings themselves aren't entirely a surprise, the paper provides clear confirmation and a detailed explanation of the mechanism through which the protein damages vascular cells for the first time. There's been a growing consensus that SARS-CoV-2 affects the vascular system, but exactly how it did so was not understood. Similarly, scientists studying other coronaviruses have long suspected that the spike protein contributed to damaging vascular endothelial cells, but this is the first time the process has been documented.

In the new study, the researchers created a "pseudovirus" that was surrounded by SARS-CoV-2 classic crown of spike proteins, but did not contain any actual virus. Exposure to this pseudovirus resulted in damage to the lungs and arteries of an animal model--proving that the spike protein alone was enough to cause disease. Tissue samples showed inflammation in endothelial cells lining the pulmonary artery walls.

The team then replicated this process in the lab, exposing healthy endothelial cells (which line arteries) to the spike protein. They showed that the spike protein damaged the cells by binding ACE2. This binding disrupted ACE2's molecular signaling to mitochondria (organelles that generate energy for cells), causing the mitochondria to become damaged and fragmented.

Previous studies have shown a similar effect when cells were exposed to the SARS-CoV-2 virus, but this is the first study to show that the damage occurs when cells are exposed to the spike protein on its own.

"If you remove the replicating capabilities of the virus, it still has a major damaging effect on the vascular cells, simply by virtue of its ability to bind to this ACE2 receptor, the S protein receptor, now famous thanks to COVID," Manor explains. "Further studies with mutant spike proteins will also provide new insight towards the infectivity and severity of mutant SARS CoV-2 viruses."

The researchers next hope to take a closer look at the mechanism by which the disrupted ACE2 protein damages mitochondria and causes them to change shape.

###

Other authors on the study are Yuyang Lei and Zu-Yi Yuan of Jiaotong University in Xi'an, China; Cara R. Schiavon, Leonardo Andrade, and Gerald S. Shadel of Salk; Ming He, Hui Shen, Yichi Zhang, Yoshitake Cho, Mark Hepokoski, Jason X.-J. Yuan, Atul Malhotra, Jin Zhang of the University of California San Diego; Lili Chen, Qian Yin, Ting Lei, Hongliang Wang and Shengpeng Wang of Xi'an Jiatong University Health Science Center in Xi'an, China.

The research was supported by the National Institutes of Health, the National Natural Science Foundation of China, the Shaanxi Natural Science Fund, the National Key Research and Development Program, the First Affiliated Hospital of Xi'an Jiaotong University; and Xi'an Jiaotong University.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

SEE ORIGINAL STUDY



Filters close

Showing results

110 of 5857
Released: 22-Jun-2021 5:10 PM EDT
Tecnología de inteligencia artificial y ECG puede rápidamente descartar infección por COVID-19
Mayo Clinic

La inteligencia artificial puede ofrecer un manera de determinar con exactitud que una persona no está infectada con la COVID-19. Un estudio internacional y retrospectivo descubrió que la infección por SARS-CoV-2, el virus que causa la COVID-19, provoca sutiles cambios eléctricos en el corazón. Un electrocardiograma (ECG) mediado por inteligencia artificial detecta estos cambios y puede servir como una prueba rápida y confiable para descartar la infección por COVID-19.

Released: 22-Jun-2021 4:45 PM EDT
Penn Medicine to Use $1M from City of Philadelphia for Additional Community Vaccination Clinics
Perelman School of Medicine at the University of Pennsylvania

Penn Medicine will continue its collaboration with the West and Southwest Philadelphia communities to operate a series of COVID-19 vaccine clinics in partnership with community organizations, faith-based institutions, restaurants, barbershops, and even professional sports teams thanks to $1 million in funding from the City of Philadelphia, in partnership with PMHCC.

Released: 22-Jun-2021 12:30 PM EDT
Political Variables Carried More Weight Than Healthcare in Government Response to COVID-19
Binghamton University, State University of New York

Political institutions such as the timing of elections and presidentialism had a larger influence on COVID-19 strategies than the institutions organizing national healthcare, according to a research team led by a professor at Binghamton University, State University of New York.

22-Jun-2021 12:00 PM EDT
Study Testing How Well COVID-19 Vaccine Prevents Infection and Spread of SARS-CoV-2 Among University Students Now Expands to Include Young Adults Beyond the University Setting
Covid-19 Prevention Network (CoVPN)

The Prevent COVID U study, which launched in late March 2021 to evaluate SARS-CoV-2 infection and transmission among university students vaccinated with the Moderna COVID-19 Vaccine, has expanded beyond the university setting to enroll young adults ages 18 through 29 years and will now also include people in this age group who choose not to receive a vaccine.

Newswise: First Wave COVID-19 Data Underestimated Pandemic Infections
18-Jun-2021 8:30 AM EDT
First Wave COVID-19 Data Underestimated Pandemic Infections
American Institute of Physics (AIP)

Two COVID-19 pandemic curves emerged within many cities during the one-year period from March 2020 to March 2021. Oddly, the number of total daily infections reported during the first wave is much lower than that of the second, but the total number of daily deaths reported during the first wave is much higher than the second wave.

Newswise: PNNL AI Expert Harnesses Open-Source Data to Understand Human Behavior
Released: 22-Jun-2021 9:55 AM EDT
PNNL AI Expert Harnesses Open-Source Data to Understand Human Behavior
Pacific Northwest National Laboratory

PNNL researchers used natural language processing and deep learning techniques to reveal how and why different types of misinformation and disinformation spread across social platforms. Applied to COVID-19, the team found that misinformation intended to influence politics and incite fear spreads fastest.

Released: 22-Jun-2021 8:30 AM EDT
Engineering Nanobodies As Lifesavers When SARS-CoV-2 Variants Attack
Ohio State University

Scientists are pursuing a new strategy in the protracted fight against the SARS-CoV-2 virus by engineering nanobodies that can neutralize virus variants in two different ways.

Released: 21-Jun-2021 3:45 PM EDT
Rare Neurological Disorder Documented Following COVID-19 Vaccination
American Neurological Association (ANA)

In two separate articles in the Annals of Neurology, clinicians in India and England report cases of a rare neurological disorder called Guillain-Barré syndrome after individuals were vaccinated against COVID-19.

Newswise: New Analysis reveals link between birthdays and COVID-19 spread during the height of the pandemic
17-Jun-2021 12:10 PM EDT
New Analysis reveals link between birthdays and COVID-19 spread during the height of the pandemic
Harvard Medical School

Risk of SARS-CoV-2 infection increased 30 percent for households with a recent birthday in counties with high rates of COVID-19 Findings suggest informal social gatherings such as birthday parties played role in infection spread at the height of the coronavirus pandemic No birthday-bash infection jumps seen in areas with low rates of COVID-19 Households with children’s birthdays had greater risk of SARS-CoV-2 infection than with adult birthdays

Newswise: COVID-19 dual-antibody therapies effective against variants in animal study
Released: 21-Jun-2021 10:05 AM EDT
COVID-19 dual-antibody therapies effective against variants in animal study
Washington University in St. Louis

A study from Washington University School of Medicine in St. Louis suggests that many, but not all, COVID-19 therapies made from combinations of two antibodies are effective against a wide range of virus variants, and that combination therapies appear to prevent the emergence of drug resistance.


Showing results

110 of 5857

close
1.63757