Virus-attacking cell molecule diminishes with age, may explain severe COVID-19 cases


A group of tiny molecules that attack invading viruses are diminished with age and chronic illnesses, according to a study which says this decrease may explain why older individuals are vulnerable to COVID-19.

Researchers, including those from the University of Florida in the US, said microRNAs play a major role in controlling the activity of genes in the body, and are also on the front line when viruses enter cells. 

The study, published in the journal Aging and Disease, noted that microRNAs latch onto and cut the RNA of invading viruses. 

However, with age and some chronic medical conditions, the attacking microRNA numbers dwindle, reducing our ability to respond to viruses, said Carlos M. Isales, study co-author from Augusta University in the US.

The novel coronavirus is then better able to hijack the host cell machinery to replicate, the researchers said. 

In the study, the scientists looked at the RNA sequence of 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. 

The researchers used computer simulation to figure out how the viral RNAs would fit together with the microRNAs. 

They tested the binding of the tiny molecules with four samples of SARS, and 29 samples of SARS-CoV-2, taken between January and April 2020 covering 17 countries including the US and Germany.

According to the study, 848 microRNAs could target the SARS genome, and 873 microRNAs targeted the SARS-CoV-2 genome. 

The scientists said 558 of the microRNAs fighting SARS were 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, they said. 

These may ultimately be found to be the most proficient at fighting the virus, the researchers said.

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. 

Many of these tiny RNA molecules are known to become diminished in number with age and with underlying medical conditions like diabetes and cardiovascular disease, the scientists said.

The study noted that low numbers of the microRNAs are a factor in the increased disease presentation and death rates seen in such risk prone individuals.

Citing an example, the researchers said microRNAs like miR-15b-5p, which has a high affinity for SARS-CoV-2, is produced less in people with coronary artery disease. 

In healthy, younger people, these are more apt to do as they should and prevent replication, said study co-author Sadanand Fulzele from Augusta University.

Of the 29 worldwide samples of SARS-CoV-2, the study said 19 had identical microRNAs, indicating that the virus has a fairly uniform presence internationally.

Based on this, the researchers believe that any effective treatment or vaccine should have a broad impact on the disease.

“My perspective is there is a key set of microRNAs that are important in triggering this abnormal response, in making older patients more susceptible,” said study senior author Carlos Isales from Augusta University.

“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,” Isales said.

The scientists believe that a novel treatment approach where cocktails of multiple key microRNA, potentially given through the nose, may help restore sufficient levels of the key virus fighters.

They also hope to understand from further studies if 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. PTI

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