BREAKING! COVID-19 Genomics: SARS-CoV-2 Genome Binding Site Targeting Host MicroRNA miR197-5p Has Mutated More Than 40 Times. Cardiovascular Implications
: University Of Otago-New Zealand researchers studying the SARS-CoV-2 coronavirus has discovered that a particular binding site of virus targeting host microRNA miR197-5p has mutated more than 40 times since March and is now present in more than 75 percent of SARS-CoV-2 global isolates. The findings also have implications for cardiovascular issues.
The research findings were published in the journal: International Journal of Molecular Sciences
When their laboratory was locked down during the Level 4 period, Ph.D. student Dr Ali Hosseini and Professor Dr Alex McLellan from the Department of Microbiology and Immunology worked from their homes to tackle a new field within the pathogenesis of COVID-19.
Dr Hosseini, lead author says he hopes this work will contribute to a better understanding of how the virus escapes the host immune response and contribute to the development of attenuated viral vaccines.
The study team put into action their skills in microRNA (miRNA) gained from their usual topic of study of anti-cancer CAR T cells, to examine previously unrecognized weak points on the SARS-2 genome that could be used to destroy the virus or help create new vaccines.
Typically, these weak points on the virus are target sites recognized by host miRNA ie a nucleic acid-based 'immune system' operating in all of our body's cells.
Basically essential for controlling gene expression within the cell, miRNAs are also important players in the recognition and destruction of viruses.
Interestingly one target site on SARS-CoV-2 matches an abundant miRNA (miR197-5p) present in very high levels in patients with cardiovascular complications or with respiratory viral infections.
It was found that these miR197-5p binding site on SARS-2 had been independently mutated nearly 40 times since March this year. This mutation is now present in more than 75 percent of SARS-2 global isolates.
Professor McLellan told Thailand Medical News, "Patients with cardiovascular complications have been shown to be at risk from COVID-19 Our study suggests that a normal defense pathway in these patients may have been blocked through this mutation in the virus."
But, he says it is too early to say if such mutations will help the virus, or are simply neutral hitchhikers that confer no advantage to the virus.
He added, "We need direct experimental approaches using live virus, as well further study of the transmission of such mutants around the world. Even so, it was surprising to find how often the miR197 target site had been mutated in different SARS-2 isolates. Our study just says: let's keep an eye on these sites and see what happens to these in future."
Dr Hosseini says because many miRNA are different between species, the newly emerged 'zoonotic' SARS-2 may face signature human miRNA attack, not previously experienced in bats.
The genomic researchers say their findings
also open up the possibility to engineer in artificial miRNA sites. This may be useful for weakening the virus for vaccine research and has been successfully performed experimentally for other respiratory viruses.
However he too warns that attention should be paid on these mutating sites as there could be other implications.
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