Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2

Influenza A virus’s (IAV’s) frequent genetic changes challenge vaccine strategies and engender resistance to current drugs. We sought to identify conserved and essential RNA secondary structures within IAV’s genome that are predicted to have greater constraints on mutation in response to therapeutic targeting. We identified and genetically validated an RNA structure (packaging stem–loop 2 (PSL2)) that mediates in vitro packaging and in vivo disease and is conserved across all known IAV isolates. A PSL2-targeting locked nucleic acid (LNA), administered 3 d after, or 14 d before, a lethal IAV inoculum provided 100% survival in mice, led to the development of strong immunity to rechallenge with a tenfold lethal inoculum, evaded attempts to select for resistance and retained full potency against neuraminidase inhibitor-resistant virus. Use of an analogous approach to target SARS-CoV-2, prophylactic administration of LNAs specific for highly conserved RNA structures in the viral genome, protected hamsters from efficient transmission of the SARS-CoV-2 USA_WA1/2020 variant. These findings highlight the potential applicability of this approach to any virus of interest via a process we term ‘programmable antivirals’, with implications for antiviral prophylaxis and post-exposure therapy

Physiological and biochemicals changes modulated by seeds’ priming of lentil (Lens culinaris L.) under salt stress at germination stage

Seed priming is one of the potential physiological approaches to enhance the seed germination under the salinity stress. The present study examined the role of two seed priming molecules: salicylic acid (SA) and hydrogen peroxide (H2O2), in enhancing the salt tolerance of lentil seeds at germination stage. Salinity stress caused significant decrease in germination percentage and primary root elongation. This decrease was associated with significant increase in lipid peroxidation and total lipid (TL) contents in embryonic axis. The catalase (CAT), guaiacol peroxydase (GPOX) and superoxide dismutase (SOD) activities remained unchanged or decreased significantly under the influence of salt stress, in both embryonic axis and cotyledons. Starch mobilization was not affected by the salt stress. The two priming treatments effectively alleviated the negative effects of salinity stress. SA and H2O2 applications after dose optimization resulted in a significant enhancement of germination percentage and primary root elongation. No significant changes in starch, soluble sugars contents and SOD activity were detected following SA and H2O2 treatments. Seed priming treatments triggered the activities of GPOX and CAT and caused the reduction in lipid peroxidation, especially in embryonic axis. TL content and especially the fatty acid C18:3 increased after SA applications. Better performance under salt stress of primed lentil seeds was associated with lower lipid peroxidation, and activation of enzymatic antioxidative defense system. Obtained results confirm the potential for using SA and H2O2 to improve germination and plant growth under salt stress conditions