14 September 2020

RNA against coronaviruses?

Russian scientists have discovered biomolecules that suppress all coronaviruses

RIA News

Researchers from the Higher School of Economics have discovered microRNA molecules potentially capable of suppressing the replication of all human coronaviruses, including SARS-CoV-2. The results of the study are published in the journal PeerJ (Nersisyan et al., Potential role of cellular miRNAs in coronavirus-host interplay).

There are seven human coronaviruses. Four of them – HCoV-OC43, HCoV-NL63, HCoV-HKU1 and HCoV-229E – are widespread and manifest as a common cold, the other three – MERS-CoV, SARS-CoV and SARS-CoV-2, cause life-threatening atypical pneumonia and other complications.

Scientists of the HSE Faculty of Biology and Biotechnology, led by Stepan Nersisyan and Alexander Tonevitsky, have identified four families of human microRNAs – small RNAs responsible for regulating gene expression – that have binding sites with all these viruses.

hsa-miR.jpg

miRNA miRNA binding sites hsa-miR-21-3p and hsa-miR-421, common to six of the seven human coronaviruses. A drawing from an article in PeerJ.

After the virus enters a healthy cell, it begins to actively interact with intracellular biomolecules, among which there are microRNAs potentially capable of suppressing viral replication. By binding to viral RNA, they destroy it. A powerful attack of microRNAs can stop the spread of the virus, with weak interaction they slow down its replication.

The latter scenario only benefits the pathogen, as it helps to avoid a rapid immune response in the cell. Some viruses even purposefully accumulate binding sites with the host microRNA. This becomes their advantage: viruses with a large number of binding sites survive and multiply better, which leads to their evolutionary predominance.

After analyzing the interactions of the virus with microRNA in the lungs of mice infected with SARS-CoV, the researchers found that the infection leads to an eight-fold increase in the expression of the hsa-miR-21-3p molecule. The same microRNA has a great potential to suppress all human coronaviruses.

Scientists wondered why the virus in the process of mutation did not eliminate in its RNA binding sites with this molecule, which, with an immune response, is aimed at its destruction.

"On the contrary, we see that the virus accumulates them in its genome during evolution. Our research shows that such sites are present in all human coronaviruses and do not undergo significant mutations. We assume that in this way the virus uses this microRNA to slow down its replication in the early stages of infection in order to delay the active immune response," Stepan Nersisyan's words are quoted in a university press release.

At the next stage, the scientists plan to experimentally test their assumptions, as well as determine whether artificial introduction or removal of microRNAs can prevent the virus from multiplying.

The researchers hope that the microRNAs they discovered can be used in the future to create new drugs and methods for treating coronavirus infections.

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