Targeting cellular response to SARS-CoV-2 holds promise as new way to fight infection
2021-06-17
(Press-News.org) A new treatment approach focused on fixing cell damage, rather than fighting the virus directly, is effective against SARS-CoV-2 in lab models.
Combination of two drugs reduces spread of SARS-CoV-2 infection in cells by up to 99.5%.
If found safe for human use, this anti-viral treatment would make
COVID-19 symptoms milder and speed up recovery times.
When a person is infected with SARS-CoV-2, the virus that causes COVID-19, it invades their cells and uses them to replicate - which puts the cells under stress. Current approaches to dealing with infection target the virus itself with antiviral drugs. But Cambridge scientists have switched focus to target the body's cellular response to the virus instead.
In a new study, published today in the journal PLOS Pathogens, they found that all three branches of a three-pronged signalling pathway called the 'unfolded protein response' (UPR) are activated in lab-grown cells infected with SARS-CoV-2. Inhibiting the UPR to restore normal cell function using drugs was also found to significantly reduce virus replication.
"The virus that causes COVID-19 activates a response in our cells - called the UPR - that enables it to replicate," said Dr Nerea Irigoyen in the University of Cambridge's Department of Pathology, senior author of the report.
She added: "Using drugs we were able to reverse the activation of this specific cellular pathway, and remarkably this reduced virus production inside the cells almost completely, which means the infection could not spread to other cells. This has exciting potential as an anti-viral strategy against SARS-CoV-2."
Treatment with a drug that targets one prong of the UPR pathway had some effect in reducing virus replication. But treatment with two drugs together - called Ceapin-A7 and KIRA8 - to simultaneously target two prongs of the pathway reduced virus production in the cells by 99.5%. This is the first study to show that the combination of two drugs has a much greater effect on virus replication in cells than a single drug.
The approach would not stop a person getting infected with the coronavirus, but the scientists say symptoms would be much milder, and recovery time would be quicker.
Anti-viral drugs currently in use to treat COVID-19, such as remdesivir, target replication of the virus itself. But if the virus develops resistance to these drugs they will no longer work. In contrast, the new treatment targets the response of the infected cells; this will not change even if new variants emerge, because the virus needs this cellular response in order to replicate.
The next step is to test the treatment in mouse models. The scientists also want to see whether it works against other viruses, and illnesses such as pulmonary fibrosis and neurological disorders that also activate the UPR response in cells.
"We hope this discovery will enable the development a broad-spectrum anti-viral drug, effective in treating infections with other viruses as well as SARS-CoV-2. We've already found it has an effect on Zika virus too. It has the potential to have a huge impact," said Irigoyen.
SARS-CoV-2 is the novel coronavirus responsible for the COVID-19 pandemic. Since the end of 2019 there have been over 150 million cases of the disease worldwide, and over 3 million people have died.
INFORMATION:
ELSE PRESS RELEASES FROM THIS DATE:
2021-06-17
Patents with all-female inventor teams are more likely than all-male teams to address problems that specifically or disproportionately affect women, according to a new study. The findings, derived from an analysis of more than 440,000 U.S. biomedical patents filed from 1976 to 2010, suggest that who benefits most from innovation largely depends on who gets to invent. While the gender gap in research and innovation is well known, its broader impact on what gets invented - and for whom - isn't well understood. To address this question, Rembrand Koning and colleagues used machine learning text analysis to evaluate all U.S. biomedical patents filed from 1976 to 2010. They found that patents ...
2021-06-17
Daunting and uncertain is the future for people who must decide whether, where, when, and how to vacate their homes as the climate changes. Communities who will absorb this influx of uprooted people also face challenges. In a special issue of Science, "Fallback Strategies: Planning for Climate-Induced Relocation," experts examine ways in which interdisciplinary basic and applied research can - and must - engage with and support communities and governments navigating this landscape. As this work is done, "we must consider not only what science can do, but how science ...
2021-06-17
Using LIGO's suspended mirrors, researchers have demonstrated the ability to cool a large-scale object - the 10-kilogram optomechanical oscillator the suspended mirrors form - to nearly the motional quantum ground state. Upgrading LIGO (Laser Interferometer Gravitational-Wave Observatory) with such a modification would not only increase the device's sensitivity and range in detecting gravitational waves but could also provide new insights into large-scale quantum phenomena. For most mechanical objects to be coaxed into a quantum state, they need to be cooled to exceedingly low temperatures to overcome the thermal vibrations, or phonons, that mask the signature of quantum motion. This brings the ...
2021-06-17
Marine-terminating glaciers may be less vulnerable to rapid and irreversible collapse than previously suggested, according to a new study, which finds that ice cliff collapse is limited by upstream thinning of the ice sheet and how quickly calved icebergs and sea-ice float away. The glaciers of Greenland and Antarctica slowly flow to the sea, terminating in massive vertical ice cliffs. Occasionally, these partially submerged margins can collapse under their own weight and trigger rapid disintegration of ice sheets. It's thought that this process, called marine ice cliff instability (MICI), could lead to the catastrophic retreat of some of the planet's largest ice sheets, substantially contributing to global sea level rise. However, current ...
2021-06-17
CAMBRIDGE, MA -- To the human eye, most stationary objects appear to be just that -- still, and completely at rest. Yet if we were handed a quantum lens, allowing us to see objects at the scale of individual atoms, what was an apple sitting idly on our desk would appear as a teeming collection of vibrating particles, very much in motion.
In the last few decades, physicists have found ways to super-cool objects so that their atoms are at a near standstill, or in their "motional ground state." To date, physicists have wrestled small objects such as clouds of millions of atoms, or nanogram-scale objects, into such pure quantum states.
Now for the first time, scientists at MIT and elsewhere have cooled a large, human-scale object to close to its motional ground state. The object ...
2021-06-17
Research conducted by Qiang et al has discovered a link between a protein in red blood cells and age-related decline in cognitive performance. Published in the open access journal PLOS Biology on 17th June 2021, the study shows that depleting mouse blood of the protein ADORA2B leads to faster declines in memory, delays in auditory processing, and increased inflammation in the brain.
As life expectancies around the world increase, so are the number of people who will experience age-related cognitive decline. Because the amount of oxygen in the blood also declines with age, the team hypothesized that ...
2021-06-17
CLEVELAND--Case Western Reserve University researchers studying prions--misfolded proteins that cause lethal incurable diseases--have identified for the first time surface features of human prions responsible for their replication in the brain.
The ultimate goal of the research is to help design a strategy to stop prion disease in humans--and, ultimately, to translate new approaches to work on Alzheimer's and other neurodegenerative diseases.
Scientists have yet to discover the exact cause of Alzheimer's disease, but largely agree that protein issues play a role in its emergence and progression. Alzheimer's disease afflicts more than 6 million people in the U.S., and the Alzheimer's Association ...
2021-06-17
UTICA, NY -- More than 2 million coronary artery stents are implanted each year to help protect or restore normal blood flow to the heart, to treat patients suffering from angina or a heart attack due to coronary artery disease (CAD). While stents are highly effective and safe devices, scarring or clotting of unhealed stents can occur in a small percentage of subjects, leading to complications such as stent restenosis or thrombosis, which can be life-threatening. At present, approaches to understand stent healing based on their biological clotting status is unavailable in patients.
To devise a potential solution to this problem, Dr. Jason McCarthy, an Associate Professor at the Masonic Medical Research Institute (MMRI), and his team have developed a fluorescent probe that binds ...
2021-06-17
A long-term passive rewilding study has shown that natural woodland regeneration could make a significant contribution to meeting the UK's ambitious tree planting targets - potentially at no cost and within relatively short timescales.
The research, led by the UK Centre for Ecology & Hydrology (UKCEH), found natural growth due to seed dispersal by birds, mammals and wind can produce biodiverse and resilient woodland.
Woodland development can be rapid, while avoiding the cost, management and plastic tubing involved in planting schemes.
The study - published in the journal PLOS ONE - found that after just 15 years, previously bare agricultural ...
2021-06-17
Physicists at Ludwig-Maximilian University in Munich (LMU) and the Max Planck Institute for Quantum Optics (MPQ) have used ultrashort laser pulses to probe the dynamics of photoelectron emission in tungsten crystals.
Almost a century ago, Albert Einstein received the Nobel Prize for Physics for his explanation of the photoelectric effect. Published in 1905, Einstein's theory incorporated the idea that light is made up of particles called photons. When light impinges on matter, the electrons in the sample respond to the input of energy, and the interaction gives rise to what is known as the photoelectric effect. Light quanta (photons) are absorbed by the ...
LAST 30 PRESS RELEASES:
[Press-News.org] Targeting cellular response to SARS-CoV-2 holds promise as new way to fight infection
