The virus that causes severe acute respiratory syndrome (SARS) produces very small RNA molecules (svRNA) that are responsible in part for the intense lung inflammation characteristic of infected patients. This is demonstrated in a study by researchers from the Centro Nacional de Biotecnología of the CSIC (CNB-CSIC) published recently in the scientific journal Cell Host & Microbe.
The scientists also showed that inhibiting these small RNAs in infected rodents greatly reduces inflammation. "Our study suggests that these svRNAs could be good targets for treatment of patients infected with SARS, a disease for which there are so far no available vaccines or antivirals," said Luis Enjuanes, a CNB-CSIC researcher and one of the authors of the study.
A virus that emerged in 2002 for which there is no vaccine or treatment.
The SARS virus originated in China in 2002 and in humans produces a very severe pulmonary pathology that leads to death in 10% of young patients and up to 50% in the elderly.
Although the virus is not currently circulating in the human population, it continues to be present in animals such as the bat. The worldwide distribution of these flying mammals increases the possibilities that, as in 2002, there will be future outbreaks of human infection. This also happened with a related coronavirus (MERS-CoV) that emerged in the Middle East in 2012.
All organisms, including many viruses, produce small non-coding RNAs in their cells. "For the first time we have detected the presence of svRNAs derived from the SARS coronavirus in the lungs of infected mice. But even more interesting is that, when we administered inhibitors to one of these svRNAs by inhalation to infected mice, lung damage was significantly reduced," explains Isabel Sola, CNB-CSIC researcher and author of the study.
Although experiments showed that inhibiting small RNAs did not reduce the animal’s viral load, it did decrease the inflammatory pathology and pulmonary oedema associated with the disease. According to the scientists, this indicates that the RNAs do not act directly on the replication mechanism of the virus, but promote the host’s inflammatory response.
"The use of small RNA inhibitors as an antiviral therapy has several advantages over other strategies. They are very specific and side effects are avoided. They can also be used in combination with other antiviral therapies to increase effectiveness and safety," says Lucía Morales, CNB-CSIC researcher and author of the study.
"Our work in rodents is a proof of concept that shows the clear therapeutic potential of these small RNA inhibitors in viral infections. It is nonetheless necessary to continue working to optimize dosage and administration parameters that improve the survival results of the animals,"explains Sola.
The scientists conclude, "Understanding the molecular mechanisms by which svRNAs contribute to lung inflammation will help design new antivirals against the pulmonary pathology of SARS."
- Morales L, Oliveros JC, Fernandez-Delgado R, tenOever BR, Enjuanes L, Sola I. SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology. Cell Host Microbe. 2017 Feb 12. pii: S1931-3128(17)30037-9. doi: 10.1016/j.chom.2017.01.015