Testing novel generation antisense oligonucleotides for potential therapeutic use in COVID-19 infections.

Valerio Orlando's lab is exploring the possibility of using novel generation antisense oligonucleotides as an adjuvant in therapeutic treatment of COVID-19 patients. The idea stems from recent cases reported from hospitals in Italy and China in which some patients treated with anti-inflammatory compounds against rheumatoid arthritis, in combination with conventional antiviral drugs, had important beneficial effects with complete remission of the disease.

Inflammation is a defense/protective mechanism initiated by signaling molecules (cytokines) that activate the production of endogenous factors that are activated when cells are challenged by pathogens.  

However, in certain acute conditions—like infections with aggressive retroviruses (SARs, MERs, coronavirus)—where, for example, alveolar epithelia are severely damaged by viral replication and bacterial infections, the high rate of inflammatory response may overtake the capacity of the immune system. In this situation, interferon response loses control, starting the production of uncontrolled levels of cytokines (a "cytokine storm") and provoking severe damage in the tissues. This contributes to the high rate of fatal prognosis in the case of COVID-19 patients.

Recent work from Orlando's lab identified new targets potentially involved in this process. The group has successfully used the activity of novel generation reagents against such targets in various disease model systems. Action that has been taken is aimed at collaboration with international and national laboratories and clinical centers potentially testing this idea, with the scope/hope to accelerate the identification of novel, effective, low toxicity adjuvant treatment against COVID-19.