Penta-Covid Platform for SARS CoV-2 (Covid-19)


Disease Background: SARS-CoV-2 the causative agent of COVID-19 was first detected in Wuhan, China, in December 2019. Hoffmann et al., 2020, established that SARS-CoV-2 depends on angiotensin-converting enzyme 2 (ACE2) for entry into cells. ACE2 is a type I transmembrane metallocarboxypeptidase predominantly expressed in vascular endothelial cells, the renal tubular epithelium, and in Leydig cells of the testes. Once the virus enters into the host and replicates, it continues to evade the immune system through the use of glycosylation shield. This evasive nature of spike protein through glycosylation has been implicated as an important step in the successful viral multiplication and mode of pathophysiology in the host. Following multiplication in the host, SARS-CoV-2 is able to induce a cytokine storm leading to hypercoagulopathy and microangiopathy with concomitant collapsing glomerulopathy and sepsis that precedes mortality.


Details on the Model: Pentagrit Humanized zebrafish model of SARS-CoV-2 demonstrates absorbance of spike protein into the system using zebrafish carrying human lung epithelia. The subsequent steps include an anomaly of the swim bladder akin to human lungs with a disintegrating and myolytic pathology, the cytology of the swim bladder is observed as inflammatory infiltration with both innate immunity of granulocytes and macrophages and adaptive immunity lymphocytes present. Further there is a disintegration of the smooth muscle fibers indicative of myolysis observed as a structural anomaly in the size of the swim bladder indicated with a deflating inner space. This pathology is also associated with increased space between the inner and outer tunic layer of the swim bladder due to the accumulation of fluids. A complete weakening of the organ architecture due to both discoloration and structural deviation is observed in the swim bladder. This is followed by glomerulopathy with the loss of tubular segments and vascular degeneration with indications of severe hemorrhage, proceeding as renal necrosis across the entire kidney eventuating to a collapsing glomerulopathy followed by mortality. Dexamethasone rescues inflammatory cytokine response induced injury in the zebrafish model of Covid-19.