Glycolytic stress deteriorates 229E virulence to improve host defense response.

Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose (2-DG), a molecule restricting substrate availability, has recently gained attention as a potential antiviral drug. The results revealed that 229E human coronavirus promoted glycolysis, producing a significant increase in the concentration of fluorescent 2-NBDG, a glucose analog, particularly in the infected host cells. The addition of 2-DG decreased its viral replication and suppressed infection-induced cell death and cytopathic effects, thereby improving the antiviral host defense response. It was also observed that administration of low doses of 2-DG inhibited glucose uptake, indicating that 2-DG consumption in virus-infected host cells was mediated by high-affinity glucose transporters, whose levels were amplified upon coronavirus infection. Our findings indicated that 2-DG could be a potential drug to improve the host defense system in coronavirus-infected cells.

Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses.