Nicorandil for COVID-19

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the Coronavirus disease 2019 (COVID-19) pandemic, has posed significant healthcare challenges. In addition to respiratory complications, it has led to severe damage in other organs, particularly the cardiovascular system. Of which, myocardial injury is increasingly recognized as a most significant complication, contributing to the high mortality. Recent research indicates the pivotal role of immune dysregulation in mediating myocardial injury in patients infected with SARS-CoV-2. In this review, we provide a comprehensive analysis of the immune mechanisms involved in SARS-CoV-2-induced myocardial damage, focusing on the roles of key immune cells and molecules that contribute to this pathological process. Aiming at mitigating the myocardial injury of COVID-19, we review immune-based treatments under evaluation in preclinical and clinical trials. Along with talking about the similarities and differences in myocardial injury resulting from SARS-CoV-2, the Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus (SARS-CoV). This article provides a unique perspective on using past experiences to prevent myocardial injury in the face of ongoing virus mutations.

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.