Role of Multifunctional Cytoskeletal Filaments in Coronaviridae Infections: Therapeutic Opportunities for COVID-19 in a Nutshell.

A novel coronavirus discovered in 2019 is a new strain of the Coronaviridae family (CoVs) that had not been previously identified in humans. It is known as SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2, whilst COVID-19 is the name of the disease associated with the virus. SARS-CoV-2 emerged over one year ago and still haunts the human community throughout the world, causing both healthcare and socioeconomic problems. SARS-CoV-2 is spreading with many uncertainties about treatment and prevention: the data available are limited and there are few randomized controlled trial data on the efficacy of antiviral or immunomodulatory agents. SARS-CoV-2 and its mutants are considered as unique within the Coronaviridae family insofar as they spread rapidly and can have severe effects on health. Although the scientific world has been succeeding in developing vaccines and medicines to combat COVID-19, the appearance and the spread of new, more aggressive mutants are posing extra problems for treatment. Nevertheless, our understanding of pandemics is increasing significantly due to this outbreak and is leading to the development of many different pharmacological, immunological and other treatments. This Review focuses on a subset of COVID-19 research, primarily the cytoskeleton-related physiological and pathological processes in which coronaviruses such as SARS-CoV-2 are intimately involved. The discovery of the exact mechanisms of the subversion of host cells by SARS-CoV-2 is critical to the validation of specific drug targets and effective treatments.

Dexamethasone and transdehydroandrosterone significantly reduce pulmonary epithelial cell injuries associated with mechanical ventilation.

Many patients who suffer from pulmonary diseases cannot inflate their lungs normally, as they need mechanical ventilation (MV) to assist them. The stress associated with MV can damage the delicate epithelium in small airways and alveoli, which can cause complications resulting in ventilation-induced lung injuries (VILIs) in many cases, especially in patients with acute respiratory distress syndrome (ARDS). Therefore, efforts were directed to develop safe modes for MV. In our work, we propose a different approach to decrease injuries of epithelial cells (EpCs) upon MV. We alter EpCs' cytoskeletal structure to increase their survival rate during airway reopening conditions associated with MV. We tested two anti-inflammatory drugs dexamethasone (DEX) and transdehydroandrosterone (DHEA) to alter the cytoskeleton. Cultured rat L2 alveolar EpCs were exposed to airway reopening conditions using a parallel-plate perfusion chamber. Cells were exposed to a single bubble propagation to simulate stresses associated with mechanical ventilation in both control and study groups. Cellular injury and cytoskeleton reorganization were assessed via fluorescence microscopy, whereas cell topography was studied via atomic force microscopy (AFM). Our results indicate that culturing cells in media, DEX solution, or DHEA solution did not lead to cell death (static cultures). Bubble flows caused significant cell injury. Preexposure to DEX or DHEA decreased cell death significantly. The AFM verified alteration of cell mechanics due to actin fiber depolymerization. These results suggest potential beneficial effects of DEX and DHEA for ARDS treatment for patients with COVID-19. They are also critical for VILIs and applicable to future clinical studies.NEW & NOTEWORTHY Preexposure of cultured cells to either dexamethasone or transdehydroandrosterone significantly decreases cellular injuries associated with mechanical ventilation due to their ability to alter the cell mechanics. This is an alternative protective method against VILIs instead of common methods that rely on modification of mechanical ventilator modes.