Secreted Protein Acidic and Rich in Cysteine (SPARC) to Manage Coronavirus Disease-2019 (COVID-19) Pandemic and the Post-COVID-19 Health Crisis.

Coronavirus disease-2019 (COVID-19) has had and will have impacts on public health and health system expenses. Indeed, not only it has led to high numbers of confirmed COVID-19 cases and hospitalizations, but its consequences will remain even after the end of the COVID-19 crisis. Therefore, therapeutic options are required to both tackle the COVID-19 crisis and manage its consequences during the post COVID-19 era. Secreted protein acidic and rich in cysteine (SPARC) is a biomolecule that is associated with various properties and functions that situate it as a candidate which may be used to prevent, treat and manage COVID-19 as well as the post-COVID-19-era health problems. This paper highlights how SPARC could be of such therapeutic use.

A Review on COVID-19: Primary Receptor, Endothelial Dysfunction, Related Comorbidities, and Therapeutics

Since December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic named coronavirus disease-19 (COVID-19) and resulted in a worldwide economic crisis. Utilizing the spike-like protein on its surface, the SARS-CoV-2 binds to the receptor angiotensin-converting enzyme 2 (ACE2), which highly expresses on the surface of many cell types. Given the crucial role of ACE2 in the renin–angiotensin system, its engagement by SARS-CoV-2 could potentially result in endothelial cell perturbation. This is supported by the observation that one of the most common consequences of COVID-19 infection is endothelial dysfunction and subsequent vascular damage. Furthermore, endothelial dysfunction is the shared denominator among previous comorbidities, including hypertension, kidney disease, cardiovascular diseases, etc., which are associated with an increased risk of severe disease and mortality in COVID-19 patients. Several vaccines and therapeutics have been developed and suggested for COVID-19 therapy. The present review summarizes the relationship between ACE2 and endothelial dysfunction and COVID-19, also reviews the most common comorbidities associated with COVID-19, and finally reviews several categories of potential therapies against COVID-19.

Early Clinical Development of Lufotrelvir as a Potential Therapy for COVID-19

Lufotrelvir was designed as a first in class 3CL protease inhibitor to treat COVID-19. Development of lufotrelvir was challenged by its relatively poor stability due to its propensity to epimerize and degrade. Key elements of process development included improvement of the supply routes to the indole and lactam fragments, a Claisen addition to homologate the lactam, and a subsequent phosphorylation reaction to prepare the prodrug as well as identification of a DMSO solvated form of lufotrelvir to enable long-term storage. As a new approach to preparing the indole fragment, a Cu-catalyzed C-O coupling using oxalamide ligands was demonstrated. The control of process-related impurities was essential to accommodate the parenteral formulation. Isolation of an MEK solvate followed by the DMSO solvate ensured that all impurities were controlled appropriately. © 2023 American Chemical Society.

How glycobiology can help us treat and beat the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged during the last months of 2019, spreading throughout the world as a highly transmissible infectious illness designated as COVID-19. Vaccines have now appeared, but the challenges in producing sufficient material and distributing them around the world means that effective treatments to limit infection and improve recovery are still urgently needed. This review focuses on the relevance of different glycobiological molecules that could potentially serve as or inspire therapeutic tools during SARS-CoV-2 infection. As such, we highlight the glycobiology of the SARS-CoV-2 infection process, where glycans on viral proteins and on host glycosaminoglycans have critical roles in efficient infection. We also take notice of the glycan-binding proteins involved in the infective capacity of virus and in human defense. In addition, we critically evaluate the glycobiological contribution of candidate drugs for COVID-19 therapy such as glycans for vaccines, anti-glycan antibodies, recombinant lectins, lectin inhibitors, glycosidase inhibitors, polysaccharides, and numerous glycosides, emphasizing some opportunities to repurpose FDA-approved drugs. For the next-generation drugs suggested here, biotechnological engineering of new probes to block the SARS-CoV-2 infection might be based on the essential glycobiological insight on glycosyltransferases, glycans, glycan-binding proteins, and glycosidases related to this pathology.

The application of direct viral cytopathic hypothesis to design drug trials in the battle against COVID-19.

COVID-19 has caused many deaths worldwide. Systemic complications alongside coagulopathy, and ARDS account for the majority of COVID-19 mortalities. The pathogenesis of the disease can be explained by two theories of direct viral cytopathy and systemic inflammatory cascade of events. ACE-2 is shown to be the cellular host receptor for SARS-CoV-2. It might be the key to explain the pathogenesis of systemic complications with a focus on the direct viral cytopathic hypothesis. Different medications tend to show up in many in vitro drug screens. However, more trials are needed to translate their application into in vivo efficacy.