The present global health emergency involving the emergence and rapid spread of a novel coronavirus has prompted the world scientific community to consider how it can help to fight this growing viral pandemic. With few safe and effective drugs available to combat this threat to humanity and the normal functioning of our society, the oligonucleotide research community is uniquely positioned to apply its technology and expertise to help alleviate the crisis, thanks to its capacity for rational drug design, swift development cycles, and pursuing targets undruggable by conventional treatment strategies.
A final thought on potential modes of treatment is that of activating innate immunity. Oligos with appropriate sequence and backbone modifications can be used to target TLRs to trigger protective interferon production. Interferons are so important as antiviral agents that viruses such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved proteins that block interferon activities. Conversely, oligos can perhaps be used to dampen innate immune responses to prevent inflammation. RNAs with specific sequence motifs can activate TLR7, whereas DNA oligos with CpG motifs activate TLR9. In addition, 5¢ triphosphatecontaining RNAs activate the retinoic acid-inducible gene-I (RIGI) TLR. When activated, each of these TLRs signals type 1 interferon gene expression, which can be an effective antiviral strategy.
Of course, the greatest challenge for oligo-based treatment strategies in this setting is delivery. The majority of oligo therapeutic applications utilize systemic delivery through intravenous or subcutaneous injection. In this circumstance, what is ideally needed is a form of inhalation delivery to get the oligos directly into the airways and lungs. A number of groups have pursued such a method of delivery in the past decade for respiratory diseases, and its effective implementation in patients with COVID-19 could enable many of the aforementioned strategies to be truly efficacious.
In summary, oligo-based therapies introduce a galaxy of possible applications to SARS-CoV-2 and other CoV infections (Table 1). Oligo therapeutics are easy to design, cost-effective to manufacture, and already possess many optimizing chemical modifications identified for use in other diseases, thereby simplifying design, production, and medicinal chemistry optimization during a crisis when rapid drug development is of utmost importance. As veterans of the field, the Rossi group feels it would be incredibly rewarding to witness oligo utilization to treat COVID-19 and other CoV infections
Reference& source information: https://www.liebertpub.com/
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