A group of tiny RNA that should attack the virus causing COVID-19 when it tries to infect the body are diminished with age and chronic health problems, a decrease that likely helps explain why older individuals and those with preexisting medical conditions are vulnerable populations, investigators report.
MicroRNAs play a big role in our body in controlling gene expression, and also are a front line when viruses invade, latching onto and cutting the RNA, the genetic material of the virus, says Dr. Sadanand Fulzele, aging researcher in the Department of Medicine and Center for Healthy Aging at the Medical College of Georgia at Augusta University.
But with age and some chronic medical conditions, the attacking microRNA numbers dwindle, reducing our ability to respond to viruses, says Dr. Carlos M. Isales, co-director of the MCG Center for Healthy Aging and chief of the MCG Division of Endocrinology, Diabetes and Metabolism.
Much like not having enough troops on the ground in an actual war, the coronavirus is then better able to do what it does naturally, which is hijacking our cell machinery so it can replicate, say the researchers who report in the journal Aging and Disease what appear to be key microRNA involved in responding to this virus. They have a longer-term goal of identifying the biggest hitters and replenishing those troops.
They looked at the RNA sequence of actually two coronaviruses, SARS, which surfaced in 2002, and SARS-CoV-2, which causes COVID-19, and the sequence of the microRNAs that appeared to be attacking the virus, then used computer simulation to figure out which would logically fit together like puzzle pieces. Their perusal included four samples of SARS and 29 samples of SARS-CoV-2, taken between January and April 2020 from five continents covering 17 countries from the United States to Germany to Thailand.
They found 848 microRNAs that target the SARS genome and 873 microRNAs that target SARS-CoV-2 genome. They found 558 of the microRNAs fighting SARS also present in SARS-CoV-2, while 315 microRNAs were unique to SARS-CoV-2, and 290 were unique to SARS. MicroRNAs most proficient at attacking SARS-CoV-2 showed more than 10 target sites and might ultimately be found to be the most proficient at fighting the virus, which, in a few months, has changed much of the way the world functions.
They also found the microRNAs targeting SARS-CoV-2 were associated with more than 72 biological processes — from the production of molecules to the immune response — and that many are known to become dysregulated and/or diminish in number with age and with underlying medical conditions like diabetes and cardiovascular disease, a likely factor in the increased disease presentation and death rates seen in these individuals, the investigators say.
An example is microRNAs like miR-15b-5p, which has a high affinity for SARS-CoV-2, but is downregulated in coronary artery disease, says corresponding author Fulzele. In healthy, younger people, these microRNAs whose nature is to bind to the virus, are more apt to do as they should and prevent replication, he adds.
In the 29 worldwide samples of SARS-CoV-2, 19 had identical microRNAs, which indicates the virus has a fairly uniform presence internationally and that any effective treatments or vaccines should have broad impact, Isales says.
Next steps include studies in culture and lab animals to ensure findings are consistent with the computer analysis of human microRNAs in this study.
“The most important and striking feature of COVID-19 is the increased case fatality rate in aged individuals,” the investigators write, with the CDC reporting that nearly half of patients requiring hospitalization are age 65 and older, and these more senior individuals account for about 80% of the deaths. Fulzele, Isales and their colleagues wanted to know more about why.
“My perspective is there is a key set of microRNAs that are important in triggering this abnormal response, in making older patients more susceptible,” says senior author Isales. “We are looking at microRNAs in general dropping, but there is a specific subset that is key. The question is whether we can we target those as a therapy.”
Cocktails of multiple key microRNA, potentially given through the nose, might help restore sufficient levels of the key virus fighters, the investigators say.
They already are moving toward producing synthetic microRNA that could supplement this frontline weakened by age or disease, Fulzele says. Future studies also include pinning down which microRNA would be most impactful as an adjunct therapy, for example with the drug remdesivir, under study now for COVID-19, which works to stop the virus’ pirating of healthy cell machinery.
Another question to pursue is whether some younger people, who also are seriously sickened by SARS-CoV-2 infection, already don’t make sufficient numbers of some of the key protective microRNA, Isales says.
Image Credit: Envato/Amanda Scott
Thanks to Heinz V. Hoenen. Follow him on twitter: @HeinzVHoenen
News This Week
A Promising New Pathway in the Battle Against Aggressive Prostate Cancer
Neuronal Molecule Makes Prostate Cancer More Aggressive Researchers discover a potential therapeutic avenue against an aggressive form of prostate cancer. Prostate cancer is the second most common cancer and the second leading cause of [...]
Nasal Vaccines: Stopping the COVID-19 Virus Before It Reaches the Lungs
The Pfizer-BioNTech and Moderna mRNA vaccines have played a large role in preventing deaths and severe infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve [...]
NASA Tracking a Huge, Growing Anomaly in Earth’s Magnetic Field – with video
NASA is actively monitoring a strange anomaly in Earth's magnetic field: a giant region of lower magnetic intensity in the skies above the planet, stretching out between South America and southwest Africa. This vast, developing [...]
New, Better Models Show How Infectious Diseases Like COVID-19 Spread
Infectious diseases such as COVID-19 can spread rapidly across the globe. Models that can predict how such diseases spread will strengthen national surveillance systems and improve public health decision-making. The COVID-19 pandemic has emphasized the [...]
Human Antibodies Discovered That Can Block Multiple Coronaviruses Including COVID-19
Results from a Scripps Research and UNC team pave the way for a vaccine and therapeutic antibodies that could be stockpiled to fight future coronavirus pandemics. A team of scientists from Scripps Research and [...]
Nanotechnology could be used to treat lymphedema
The human body is made up of thousands of tiny lymphatic vessels that ferry white blood cells and proteins around the body, like a superhighway of the immune system. It's remarkably efficient, but if [...]
DNA Nanotechnology Tools – From Design to Applications
Suite of DNA nanotechnology devices engineered to overcome specific bottlenecks in the development of new therapies, diagnostics, and understanding of molecular structures. DNA nanostructures with their potential for cell and tissue permeability, biocompatibility, and [...]
Regenerating bone with deer antler stem cells
Scientists from a collection of Chinese research institutions collaborated on a study of organ regeneration in mammals, finding deer antler blastema progenitor cells are a possible source of conserved regeneration cells in higher vertebrates. [...]
AI Takes On Cancer: Analysis of Mutations Could Lead to Improved Therapy
Cancer is a complex and diverse disease, and its range of associated mutations is vast. The combination of these genomic changes in an individual is referred to as their “mutational landscape.” These landscapes vary [...]
Exposing tumours to bacteria converts immune cells to cancer killers
New research on inflammation could lead to better treatments to improve outcomes for people with advanced or previously untreatable cancers. Introducing bacteria to a tumour’s microenvironment creates a state of acute inflammation that triggers [...]
Smart nanotechnology for more accurate delivery of insulin
More efficient and longer lasting glucose-responsive insulin that eliminates the need for people with type 1 diabetes to measure their glucose levels could be a step closer thanks to a Monash University-led project. Published [...]
Efficiently Harvesting Rare Earth Elements From Wastewater Using Exotic Bacteria
The novel strains of cyanobacteria exhibit a fast and efficient “biosorption” of rare earth elements, making recycling possible. Rare earth elements (REEs) are a set of 17 metallic elements that possess similar chemical properties. [...]
Resisting Treatment: Cancer Cells Shrink or Super-Size To Survive
A new approach to image analysis has uncovered how cancer cells manipulate their size as a means of resisting treatment. Researchers have discovered that cancer cells are capable of either shrinking or super-size themselves [...]
New Research Explains Why Children Avoid Severe COVID-19 Symptoms
According to new research, children exhibit a robust initial immune response to the coronavirus, however, they are unable to transfer this response to long-lasting memory T cells like adults do. Researchers led by scientists [...]
Scientists Unravel Protein Map of Mitochondria
A new study sheds light on the organization of proteins within mitochondria. Mitochondria, the “powerhouses” of cells, play a crucial role in the energy production of organisms and are involved in various metabolic and [...]
Mystifying Trapping Phenomenon: A Surprising Way To Catch a Microparticle
New insights could advance microfluidics and drug delivery systems. New study finds obstacles can trap rolling microparticles in fluid Through simulations and experiments, physicists attribute the trapping effect to stagnant pockets of fluid, created [...]