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
he United States has recorded 5 million confirmed coronavirus cases, while almost 20 million people are infected worldwide, according to Johns Hopkins University. Outside of the US, Brazil recorded more than 3 million cases, [...]
According to the first phase results, 90 per cent of the patients'lungs are still in a damaged state, which means their lungs ventilation and gas exchange functions have not recovered 90% of an example [...]
There are currently 25 vaccines to fight COVID-19 in clinical evaluation, another 139 vaccines in a pre-clinical stage, and many more being researched. But many of those vaccines, if they are at all successful, might [...]
A new class of nanosensor developed in Brazil could more accurately identify dengue and Zika infections, a task that is complicated by their genetic similarities and which can result in misdiagnosis. The technique uses [...]
Scientists investigating the evolution of the virus that causes Covid19 say that its mutation seems to be directed by human proteins that degrade it, but natural selection of the virus enables it to bounce [...]
Biomedical engineers at the Tufts University School of Engineering have developed tiny lipid-based nanoparticles that incorporate neurotranmitters to help carry drugs, large molecules, and even gene editing proteins across the blood-brain barrier and into [...]
UC San Diego recently announced that its health radiologists and other physicians are now leveraging artificial intelligence (AI) to augment lung-imaging analysis in a clinical research study aimed at COVID-19 lung imaging analysis. The cause of [...]
The hubbub around mutations in the virus that causes COVID-19—and how they might make it more infectious—has been around since the early phase of the pandemic. A preprint study about a particular mutation involving [...]
Human trials of a potential coronavirus vaccine being developed by scientists in Oxford are reported to have shown promising results. The researchers believe they have made a breakthrough after discovering the jab could provide “double protection” [...]
Researchers at MIT and Brigham and Women’s Hospital have designed a new face mask that they believe could stop viral particles as effectively as N95 masks. Unlike N95 masks, the new masks were designed [...]
Doctors may be missing signs of serious and potentially fatal brain disorders triggered by coronavirus, as they emerge in mildly affected or recovering patients, scientists have warned. Neurologists are on Wednesday publishing details of [...]
University of Wisconsin-Madison researchers have developed a safer and more efficient way to deliver a promising new method for treating cancer and liver disorders and for vaccination -- including a COVID-19 vaccine from Moderna [...]
Despite its advantages over other vaccine technologies for Covid-19, adenovirus vector vaccines are likely to be tripped up by pre-existing antibodies to the vectors used and the need for a second injection to boost [...]
When the first coronavirus cases in Chicago appeared in January, they bore the same genetic signatures as a germ that emerged in China weeks before. But as Egon Ozer, an infectious-disease specialist at the Northwestern University [...]
Park Systems presents “NanoScientific Symposium on Nano Applications for a Changing World” sponsored by Physics World and Nanotechnology World Association. Park Systems launched this online event for researchers and scientists in nanoscience and nanotechnology [...]
Notwithstanding the wishful thinking of certain irresponsible and incompetent public figures, the only options to control and deal with the spread of the Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) are fast, cheap, reliable, [...]