MitoQ for COVID-19

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.

Abstract In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases. Over the past seven decades, our understanding of the pathology and clinical characteristics of ARDS has evolved significantly, yet it remains an area of active research and discovery. ARDS is highly heterogeneous, including diverse pathological causes, clinical presentations, and treatment responses, presenting a significant challenge for clinicians and researchers. In this review, we comprehensively discuss the latest advancements in ARDS research, focusing on its heterogeneity, pathophysiological mechanisms, and emerging therapeutic approaches, such as cellular therapy, immunotherapy, and targeted therapy. Moreover, we also examine the pathological characteristics of COVID-19-related ARDS and discuss the corresponding therapeutic approaches. In the face of challenges posed by ARDS heterogeneity, recent advancements offer hope for improved patient outcomes. Further research is essential to translate these findings into effective clinical interventions and personalized treatment approaches for ARDS, ultimately leading to better outcomes for patients suffering from ARDS.

Coronavirus disease 2019 (COVID-19) causes pulmonary edema, which disrupts the lung alveoli–capillary barrier and leads to pulmonary cell apoptosis, the main cause of death. However, the molecular mechanism behind SARS-CoV-2’s apoptotic activity remains unknown. Here, we revealed that SARS-CoV-2-ORF-3a mediates the pulmonary pathology associated with SARS-CoV-2, which is demonstrated by the fact that it causes lung tissue damage. The in vitro results showed that SARS-CoV-2-ORF-3a triggers cell death via the disruption of mitochondrial homeostasis, which is modulated through the regulation of Mitochondrial ATP-sensitive Potassium Channel (MitoKATP). The addition of exogenous Potassium (K+) in the form of potassium chloride (KCl) attenuated mitochondrial apoptosis along with the inflammatory interferon response (IFN-β) triggered by SARS-ORF-3a. The addition of exogenous K+ strongly suggests that dysregulation of K+ ion channel function is the central mechanism underlying the mitochondrial dysfunction and stress response induced by SARS-CoV-2-ORF-3a. Our results designate that targeting the potassium channel or its interactions with ORF-3a may represent a promising therapeutic strategy to mitigate the damaging effects of infection with SARS-CoV-2.