Abstract
The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated the ongoing coronavirus disease-2019 (COVID-19) pandemic, still with an uncertain outcome. Besides pneumonia and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), other features became evident in the context of COVID-19. These includes endothelial and coagulation dysfunction with disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS), along with the occurrence of neurological alterations. The multi-system nature of such viral infection is a witness to the exploitation and impairment of ubiquitous subcellular and metabolic pathways for the sake of its life-cycle, ranging from host cell invasion, replication, transmission, up to a cytopathic effect and overt systemic inflammation. In this frame, alterations in cell-clearing systems of the host are emerging as a hallmark in the pathogenesis of various respiratory viruses, including SARS-CoV-2. Indeed, exploitation of the autophagy and proteasome pathways might contribute not only to the replication of the virus at the site of infection but also to the spreading of either mature virions or inflammatory mediators at both cellular and multisystem levels. In this frame, besides a pharmacological therapy, many researchers are wondering if some non-pharmacological substances might counteract or positively modulate the course of the infection. The pharmacological properties of natural compounds have gained increasing attention in the field of alternative and adjunct therapeutic approaches to several diseases. In particular, several naturally-occurring herbal compounds (mostly polyphenols) are reported to produce widespread antiviral, anti-inflammatory, and anti-oxidant effects while acting as autophagy and (immuno)-proteasome modulators. This article attempts to bridge the perturbation of autophagy and proteasome pathways with the potentially beneficial effects of specific phytochemicals and flavonoids in viral infections, with a focus on the multisystem SARS-CoV-2 infection.
Highlights
The coronavirus disease 2019 (COVID-19), generated by the novel coronavirus named SARS-CoV-2, emerged as a rapidly spreading communicable disease, still with an uncertain outcome worldwide
In search of natural-based, potentially safe autophagy/(immuno-)proteasome modulators, we focus on some selected nutraceutical compounds that are known to provide antiviral and anti-inflammatory effects in the frame of respiratory, cardiovascular, and neuronal alterations, which might be relevant for COVID-19 multisystem pathogenesis
We discussed evidence supporting the hypothesis that COVID-19 multisystem pathogenesis is bound to alterations of cell-clearing pathways within a variety of potentially affected tissues, including lungs, blood vessels, heart, and brain
Summary
The coronavirus disease 2019 (COVID-19), generated by the novel coronavirus named SARS-CoV-2, emerged as a rapidly spreading communicable disease, still with an uncertain outcome worldwide. While it might be seminal to elicit an anti-viral adaptive response in the site of infection, it is likely that during the late phases of infection, when a cytokine storm takes place, the immunoproteasome might be strongly and persistently recruited to promote an excessive immune reaction fueling autophagy impairment This is supported by the fact that immunoproteasome recruitment occurs through activation of molecular pathways such as PKC, NF-kB, JAK/STAT, AKT/mTOR, ACE/Angiotensin-II/ATR1, and TLR/RAGEs, which are known to impinge on the autophagy machinery [39,44,48,125,126,127,130,131,132,133,134,135,136]. AInGtEhsi,s way, DATMLRP4s, and IcFyNtorkeicneepstofursr,thwehrilaeltperrocmeollt-icnlgeasryisntgemsyicstienmflasmwmitahtinonh. ost cells via binding to RAGEs, TLR4, and IFN receptors, while promoting systemic inflammation
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