Investigators Discover Tiny RNA That Should Attack COVID-19 Diminish With Age, Disease

Monday, May 18, 2020 - 15:05

Researchers at the Department of Medicine and Center for Healthy Aging at the Medical College of Georgia at Augusta University have reported that 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.

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, SciTech Daily reports.

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 hijack 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.

“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.”

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.

Reference: “COVID-19 Virulence in Aged Patients Might Be Impacted by the Host Cellular MicroRNAs Abundance/Profile” by Fulzele Sadanand, Sahay Bikash, Yusufu Ibrahim, Lee Tae Jin, Sharma Ashok, Kolhe Ravindra and Isales Carlos M, 13 May 2020, Aging and Disease.

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