gms | German Medical Science

Background: The new emerging Coronavirus SARS-CoV-2 is an enveloped single-stranded positive-sense RNA virus. It does not retro-transpose into the host genome but instead encodes two replicase proteins. Once these replicases are translated in the host, the virus genome can be amplified. In this step of the life cycle, the virus genome is in the cytoplasm. At this point, miRNA regulation could target the virus and prevent the production of the replicase proteins and in the best case slice the virus genome. This intervention is only possible directly upon infection and if suitable miRNAs are loaded in RISC already. Unfortunately, none of the known human miRNAs seem to be specifically targeting the Coronavirus.

Methods: Additionally, once the virus genome has already been amplified, regulating replicase genes whether it leads to translational repression or slicing will not be highly successful by itself. Thus, it is important to select suitable targets. Given suitable targets, and employing multiple miRNAs targeting the virus will lead to 1) prevention of infection of novel cells and 2) retardation of virus amplification and packaging in already infected cells.

Results: Thereby, the disease will be controlled. Designing miRNA mimics with multiple targets in the Coronavirus genome whilst having as little potential targets in the human transcriptome is the key to controlling COVID-19. The miRNA mimics will be designed such that their mode of action will be to cleave the target RNA. As few different miRNA mimics as possible should be administered to further avoid off-target effects. These miRNA mimics can be packaged into microvesicles which would enable delivery via an inhalable spray, directly targeting the most infected/dangerous area: the upper respiratory tract.

Conclusion: The development of novel drugs is time-consuming and very involved with multiple clinical phases. To provide a proof-of-principle, the packaged miRNA mimics could be directly applied to cell culture. Their effectiveness could be monitored via qPCR and RNA-seq could help to ensure that the targets are sliced. The approach discussed here is completely different from all other current methodologies and has a high chance of being successful. Additionally, it is easily adapted to all RNA viruses which do not integrate into the host genome.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.