University of Maryland Medical Center

Cancer Drug Lessens the Toxicity of a Protein from Virus that Causes COVID-19

Discovery Opens Door to Testing More Effective Drugs for Treating COVID-19 Patients

Newswise — University of Maryland School of Medicine (UMSOM) researchers have identified the most toxic proteins made by SARS-COV-2—the virus that causes COVID-19 – and then used an FDA-approved cancer drug to blunt the viral protein’s detrimental effects. In their experiments in fruit flies and human cell lines, the team discovered the cell process that the virus hijacks, illuminating new potential candidate drugs that could be tested for treating severe COVID-19 disease patients. Their findings were published in two studies simultaneously on March 25 in Cell & Bioscience, a Springer Nature journal.

“Our work suggests there is a way to prevent SARS-COV-2 from injuring the body’s tissues and doing extensive damage,” says senior author of the study Zhe “Zion” Han, PhD, Associate Professor of Medicine and Director of the Center for Precision Disease Modeling at UMSOM. He notes that the most effective drug against Covid-19, remdesivir, only prevents the virus from making more copies of itself, but it does not protect already infected cells from damage caused by the viral proteins.

Prior to the pandemic, Dr. Han had been using fruit flies as a model to study other viruses, such as HIV and Zika. He says his research group shifted gears in February 2020 to study SARS-COV-2 when it was clear that the pandemic was going to significantly impact the U.S.

SARS-COV-2 infects cells and hijacks them into making proteins from each of its 27 genes. Dr. Han’s team introduced each of these 27 SARS-CoV-2 genes in human cells and examined their toxicity. They also generated 12 fruit fly lines to express SARS-CoV-2 proteins likely to cause toxicity based on their structure and predicted function.  

The researchers found that a viral protein, known as Orf6, was the most toxic killing about half of the human cells. Two other proteins (Nsp6 and Orf7a) also proved toxic, killing about 30-40 percent of the human cells. Fruit flies that made any one of these three toxic viral proteins in their bodies were less likely to survive to adulthood. Those fruit flies that did live had problems like fewer branches in their lungs or fewer energy-generating power factories in their muscle cells.

For the remaining experiments, the researchers focused on just the most toxic viral protein, so they could figure out what cell process the virus hijacks during infection. Dr. Han’s team found that the virus’ toxic Orf6 protein sticks to multiple human proteins that have the job of moving materials out of the cell’s nucleus—the place in the cell that holds the genome, or the instructions for life.

They then discovered that one of these human moving proteins, targeted by the virus, gets blocked by the cancer drug selinexor. The researchers tested selinexor on human cells and fruit flies making the toxic viral protein to see if the drug could help reverse the damage. Selinexor, like many cancer drugs is itself toxic.  However, after accounting for its toxic effects, the drug improved human cell survival by about 12 percent. Selinexor prevented early death in about 15 percent of the flies making the toxic viral protein. The drug also restored branches in the lungs and the energy-generators in the muscle cells. Selinexor is FDA-approved to treat certain blood cancers.

“More than 1,000 FDA-approved drugs are in clinical trials to test as treatments for Covid-19, and luckily a trial testing selinexor, the drug used in our study, is being performed already,” says Dr. Han. “If this trial proves to be successful, our data will have demonstrated the underlying mechanism for why the drug works.”

Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, commented, “Although we now have vaccines, it may still be a while before we will have Covid-19 infections under control, especially with the new variants emerging. We will need to tap into every tool in the arsenal available to protect people from needless sickness, disability or even death, and this study guides us towards a new target for potential therapeutics.”

These two studies were funded by a University of Maryland COVID-19 Accelerated Translational Incubator Pilot Grant, the University of Maryland, the Baltimore Institute for Clinical and Translational Research, and the University of Maryland School of Pharmacy Mass Spectrometry Center.

 

The researchers do not have any conflicts of interest to report.

 

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 45 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research.  With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has more than $563 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 student trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

 

SEE ORIGINAL STUDY



Filters close

Showing results

110 of 5872
Released: 24-Jun-2021 4:55 PM EDT
Virus that causes COVID-19 can find alternate route to infect cells
Washington University in St. Louis

The virus that causes COVID-19 normally gets inside cells by attaching to a protein called ACE2. Researchers at Washington University School of Medicine in St. Louis have found that a single mutation confers the ability to enter cells through another route, which may threaten the effectiveness of COVID-19 vaccines and therapeutics designed to block the standard route of entry.

Newswise: Is it a Virus or Bacteria? New Tech Rapidly Tests for COVID-19 and More
Released: 24-Jun-2021 3:05 PM EDT
Is it a Virus or Bacteria? New Tech Rapidly Tests for COVID-19 and More
Homeland Security's Science And Technology Directorate

S&T is preparing for future outbreaks/pandemics by investing in a new tech that can quickly discriminate between bacterial and viral infections so that the U.S. can triage patients and plan a response without delay.

Released: 24-Jun-2021 12:30 PM EDT
A tecnologia de IA e ECG pode descartar rapidamente a infecção por COVID-19, concluiu o estudo da Mayo Clinic
Mayo Clinic

A inteligência artificial (IA) pode oferecer uma maneira de determinar com precisão se uma pessoa não está infectada com a COVID-19. Um estudo retrospectivo internacional descobriu que a infecção pelo SARS-CoV-2, o vírus que causa a COVID-19, cria mudanças elétricas sutis no coração. Um eletrocardiograma (ECG) habilitado com IA pode detectar essas alterações e, potencialmente, ser usado como um teste de triagem rápido e confiável para descartar a infecção por COVID-19.

Released: 24-Jun-2021 12:10 PM EDT
妙佑医疗国际(Mayo Clinic)的研究发现,AI赋能的心电图技术有可能迅速排除COVID-19感染
Mayo Clinic

AI (人工智能)有可能提供准确判断一个人未感染COVID-19(2019冠状病毒病)的方法。一项国际回顾性研究发现,如果感染了导致COVID-19的SARS-CoV-2病毒,患者的心脏会产生微妙的电学变化。AI赋能的心电图(EKG)可以检测到这些变化,并有望被用于进行快速、可靠的COVID-19筛查检测,以排除COVID-19感染。

Newswise: 200421_Felgner_3205_sz-2-768x496.jpg
Released: 24-Jun-2021 11:50 AM EDT
UCI Professor Wins Spain’s Prestigious Princess of Asturias Award for Scientific Research
University of California, Irvine

Irvine, Calif., June 24, 2021 — Philip Felgner, Ph.D., professor in residence of physiology & biophysics at the University of California, Irvine, is one of seven scholars worldwide to win Spain’s prestigious Princess of Asturias Award for Technical and Scientific Research in recognition of their contributions to designing COVID-19 vaccines.

Released: 24-Jun-2021 11:00 AM EDT
New protein engineering method could accelerate the discovery of COVID-19 therapeutics
University of Michigan

Discovering and engineering nanobodies with properties suitable for treating human diseases ranging from cancer to COVID-19 is a time-consuming, laborious process.

Newswise: Decoding humans’ survival from coronaviruses
Released: 24-Jun-2021 11:00 AM EDT
Decoding humans’ survival from coronaviruses
University of Adelaide

An international team of researchers co-led by the University of Adelaide and the University of Arizona has analysed the genomes of more than 2,500 modern humans from 26 worldwide populations, to better understand how humans have adapted to historical coronavirus outbreaks.

access_time Embargo lifts in 2 days
Embargo will expire: 29-Jun-2021 4:00 PM EDT Released to reporters: 24-Jun-2021 10:35 AM EDT

A reporter's PressPass is required to access this story until the embargo expires on 29-Jun-2021 4:00 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Newswise: COVIDLockdownSimulations.jpg
Released: 24-Jun-2021 10:00 AM EDT
Pandemic Air Quality Affected By Weather, Not Just Lockdowns
Washington University in St. Louis

Using a diverse set of tools, the lab of Randall Martin shows how the pandemic did – or didn’t – affect levels of particulate matter during COVID lockdowns.

Released: 24-Jun-2021 6:05 AM EDT
Longest known SARS-CoV-2 infection of nearly 300 days successfully treated with new therapy
University of Bristol

An immunocompromised individual with the longest known PCR confirmed case of SARS-CoV-2 infection, lasting more than 290 days, has been successfully treated with two investigational monoclonal antibodies (laboratory engineered antibodies). Clinicians and researchers from the University of Bristol and North Bristol NHS Trust (NBT) worked closely to assess and treat the infection and want to highlight the urgent need for improved access to treatments for such people with persistent SARS-CoV-2 infection.


Showing results

110 of 5872

close
2.07075