SARS-CoV-2 might manipulate against its host the immunity RNAi/Dicer/Ago system Does mitochondria collapse upon COVID-19 infection?

Claude Pasquier; Alain Robichon

Coronaviruses belong to the family of positive-sense single-stranded RNA viruses that encodes a RNA dependent RNA polymerase for its replication in host membranous invaginations upon host cell infection. Usually viruses are rapidly detected in host cells by receptors that acts as sensors of foreign nucleic acids. In fungi, plants and invertebrates, the viral dsRNAs are trapped and cleaved by Dicer/ago machinerie into small interfering RNAs (siRNAs) that degrade the targeted viral messenger RNAs within the RNA-induced silencing complex (RISC) by a base pairing mechanism [5] . In mammals/humans the detection of virus-derived small RNAs has been mainly undetectable upon RNA virus infection [6] . Human unique Dicer processed long double-stranded RNA (dsRNA) and hairpin dsRNA into small interfering RNAs (siRNAs) and microRNAs respectively but its role as producer of antiviral RNAis is yet far to be admitted by many authors. However, mammalian viruses were successfully eliminated and replication inhibited in cultured host cells via synthetic small interfering RNAs (siRNAs) [6] . All these elements are in accordance with the fact that viral double-stranded RNA (dsRNA) induces a powerful and non-sequence-specific synthesis of interferon (IFN), which appears as the major molecular weapon to fight mammal RNA viruses [7] .