Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity

dsRNA as broad-spectrum antiviral therapeutics

“…have found a new class of immunostimulatory dsRNAs that potently promote the production of two kinds of IFN (IFN-I and IFN-III) while reducing the inflammation often observed with known types of immunostimulants. 1 When the new dsRNA molecules were tested in traditional cell culture as well as a complexed Human Organ Chip model of the lung that faithfully mimics its in vivo counterpart, they inhibited infection by many viruses with pandemic potential, such as SARS-CoV, SARS-CoV-2, MERS-CoV, and various influenza A strains. In a mouse model of COVID-19, the dsRNA decreased the virus by more than 1,000-fold.…”

RNA: The most attractive target in recent viral diseases

“…Interestingly, viral RNAs (especially double‐stranded RNAs “dsRNAs”) could indirectly inhibit their own particles to certain degrees through activating the innate immune responses in humans (Si et al., 2022). This under‐extensive‐research natural defensive mechanism spontaneously occurs as a result of detecting the presence of these foreign RNAs by the human immune system, which sounds the alarm by significantly increasing the production of various protective cytokines called interferons (IFNs, e.g., IFN‐I and IFN‐III) (Si et al., 2022). These IFNs, in turn, severely activate the innate immune responses in humans against the invading viruses (see Figure 1).…”

“…This fact provides a new targeting pathway for the viral RNAs and their infections through harnessing these endogenous wild antiviral responses. This could be therapeutically and clinically achieved by synthetically producing different types of therapeutic dsRNAs that mimic targeted viruses' genomes in almost all their features (i.e., by producing synthetic viral RNA analogs) (Si et al., 2022). Excessive and dangerous inflammations resulting from the administration of these analogs in the human body should be put into consideration, therapeutically combated, and controlled to avoid any undesirable and unfavorable harmful extrainflammatory reactions, responses, and adverse effects that could be induced and stimulated by this double‐edged‐sword pathway.…”

“…These overhangs can successfully bind to each other through the known Hoogsteen base pairing, generating a new dimer that strongly binds to the retinoic acid‐inducible gene I (RIG‐I) and also activates the interferon regulatory factor 3 (IRF3). This process consequently stimulates the production of, mainly, IFN‐I and IFN‐III, which inhibit the RNA virus and gradually stop its severe infection (this image was modified from Si et al., 2022). [Colour figure can be viewed at wileyonlinelibrary.com]…”

Different Types of Vaccines against Pestiviral Infections: “Barriers” for “Pestis”

“…For example, the double-strand RNA produced during genome replication can enhance the efficacy [ 119 , 120 ]. The foreign genes in the viral vector are expressed continually and induce persistent immunity [ 121 ]. The functions of foreign proteins are minimally affected due to the smaller size of the structural proteins.…”