New insights on circular RNAs and their potential applications as biomarkers, therapeutic agents, and preventive vaccines in viral infections: with a glance at SARS-CoV-2.

The occurrence of viral infections and approaches to handling them are very challenging and require prompt diagnosis and timely treatment. Recently, genomic medicine approaches have come up with the discovery of the competing endogenous RNA (ceRNA) network, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) on the basis of gene silencing. CircRNAs, as a group of non-encoded RNAs, make a loop-like structure by back-splicing through 3' and 5' ends. They are stable, abundant, specific, and highly conserved and can be quickly generated at large scales in vitro. CircRNAs have the potential to contribute in several cellular processes in a way that some serve as microRNA sponges, cellular transporters, protein-binding RNAs, transcriptional regulators, and immune system modulators. CircRNAs can even play an important role in modulating antiviral immune responses. In the present review, circRNAs' biogenesis, function, and biomarker and therapeutic potential as well as their prospective applications as vaccines against viral infections such as SARS-CoV-2 are explained. By considering their unique properties, their potential to be used as novel vaccines, biomarkers, and a therapeutic approach appears possible.

Autophagy, Unfolded Protein Response, and Neuropilin-1 Cross-Talk in SARS-CoV-2 Infection: What Can Be Learned from Other Coronaviruses.

The COVID-19 pandemic is caused by the 2019-nCoV/SARS-CoV-2 virus. This severe acute respiratory syndrome is currently a global health emergency and needs much effort to generate an urgent practical treatment to reduce COVID-19 complications and mortality in humans. Viral infection activates various cellular responses in infected cells, including cellular stress responses such as unfolded protein response (UPR) and autophagy, following the inhibition of mTOR. Both UPR and autophagy mechanisms are involved in cellular and tissue homeostasis, apoptosis, innate immunity modulation, and clearance of pathogens such as viral particles. However, during an evolutionary arms race, viruses gain the ability to subvert autophagy and UPR for their benefit. SARS-CoV-2 can enter host cells through binding to cell surface receptors, including angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1). ACE2 blockage increases autophagy through mTOR inhibition, leading to gastrointestinal complications during SARS-CoV-2 virus infection. NRP1 is also regulated by the mTOR pathway. An increased NRP1 can enhance the susceptibility of immune system dendritic cells (DCs) to SARS-CoV-2 and induce cytokine storm, which is related to high COVID-19 mortality. Therefore, signaling pathways such as mTOR, UPR, and autophagy may be potential therapeutic targets for COVID-19. Hence, extensive investigations are required to confirm these potentials. Since there is currently no specific treatment for COVID-19 infection, we sought to review and discuss the important roles of autophagy, UPR, and mTOR mechanisms in the regulation of cellular responses to coronavirus infection to help identify new antiviral modalities against SARS-CoV-2 virus.

Physiological and Immunological Causes of the Susceptibility of Chronic Inflammatory Patients to COVID-19 Infection: Focus on Diabetes.

The coronavirus disease 2019 (COVID-19) pandemic has recently emerged, which was then spread rapidly in more than 190 countries worldwide so far. According to the World Health Organization, 3,232,062 global cases of COVID-19 were confirmed on April 30th with a mortality rate of 3.4%. Notably, the symptoms are almost similar to those of flu such as fever, cough, and fatigue. Unfortunately, the global rates of morbidity and mortality caused by this disease are more and still increasing on a daily basis. The rates for patients suffering from inflammatory diseases like diabetes, is even further, due to their susceptibility to the pathogenesis of COVID-19. In this review, we attempted to focus on diabetes to clarify the physiological and immunological characteristics of diabetics before and after the infection with COVID-19. We hope these conceptions could provide a better understanding of the mechanisms involved in COVID-19 susceptibility and increase the awareness of risk to motivate behavior changes in vulnerable people for enhancing the prevention. Up to now, the important role of immune responses, especially the innate ones, in the development of the worst signs in COVID-19 infection have been confirmed. Therefore, to better control patients with COVID-19, it is recommended to consider a history of chronic inflammatory diseases as well as the way of controlling immune response in these patients.

Measurement of oxidized albumin: An opportunity for diagnoses or treatment of COVID-19.

Human serum albumin (HSA) as the most abundant protein in human blood plasma, can be a good indicator for evaluating severity of some diseases in the clinic. HSA can be find in two forms: reduced albumin (human mercaptalbumin (HMA)) and oxidized albumin (human non-mercaptalbumin (HNA)). The rate of oxidized albumin to total albumin can be enhanced in multiple diseases. Increase in HNA level have been demonstrated in liver, diabetes plus fatigue and coronary artery diseases. In liver patients, this enhancement can reach to 50-200 percent which can then lead to bacterial/viral infections and eventually death in severe conditions. Due to the induction of cytokine storm, we can say that the level of HNA in serum of coronavirus disease 2019 (COVID-19) patients may be a positive predictor of mortality, especially in patients with underlying diseases such as cardiovascular disease (CVD), diabetes, aging and other inflammatory diseases. We suggest that checking oxidized albumin in COVID-19 patients may provide new therapeutic and diagnostic opportunities to better combat COVID-19.