Cell Clearing Systems as Targets of Polyphenols in Viral Infections: Potential Implications for COVID-19 Pathogenesis

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.

Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS

“…Similar hypotheses have also emerged on the correlation between gastrointestinal and neurological symptoms of SARS-CoV-2, which may apply indeed to a variety of microorganisms, and also “prionoid” proteins. Once the gastrointestinal tract is invaded, the virus may transit to the CNS through vascular and lymphatic systems, or through the vagus nerve ( Bostancıklıoğlu, 2020a , b ; Limanaqi et al, 2020 ). The virus can even infect leukocytes and migrate with them into the brain, or alternatively, viral particles can be directly transported across the BBB to the brain.…”

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin

“…However, Cordyceps sinensis contains numerous substances, and the specific pure component responsible for the pharmacological activities remains elusive. Cordycepin is the major component in Cordyceps sinensis [ 18 , 19 ], and investigations of the positive effects of cordycepin on different diseases and health issues have boomed recently, with reviews showing its activities with anti-inflammatory effects [ 20 ], immunomodulatory effects [ 21 ], anti-diabetic effects [ 22 , 23 ], anti-hyperlipidemic effects [ 22 ], antioxidant effects [ 18 , 24 ], prevention in cardiovascular diseases [ 22 ], anti-cancer effects [ 25 ], etc.…”

Knowledge Graph-Based Approaches to Drug Repurposing for COVID-19

“…Several such inhibitors are already being investigated as COVID-19 therapeutics, and several were found in our results (bortezomib, carfilzomib, and saxagliptin). 27 …”