Therapeutic targets of Mucormycosis: ftr1 gene expression and glucose-regulated protein-78 receptor in sars cov-2 infected patients with uncontrolled diabetes mellitus-A systematic review

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) was associated with a significant incidence of both bacterial and fungal probably due to immune dysregulation. Moreover, the main crucial factor for mortality in COVID-19 with Mucormycosis (MCR) was the extensive use of steroids/monoclonal antibodies/broad-spectrum antibiotics as part of the armamentarium against COVID-19 and uncontrolled diabetes may lead to exacerbation of pre-existing fungal diseases. There are still no approved vaccines against fungal pathogens and the availability of drugs for the treatment of MCR is limited to a scarce. Based on the preliminary research and available data the present systematic review mainly aimed to evaluate therapeutic targets of MCR such as the FTR1 gene expression and glucose-regulated protein (GRP78) receptor in uncontrolled diabetes mellitus. Data showed that the gene encoding FTR1 is expressed by R. oryzae during murine infection and inhibition of FTR1 gene expression by RNA-I diminishes the virulence of the MCR. Hyperglycemia induces the over expression of the GRP78 mRNA levels 2- to 5 folds higher in the sinus, lungs, and the brain and also it increased 40% endocytosis of R. oryzae by human endothelial cells. We observed with preliminary evidence that iron chelation therapy showed beneficiary effects in MCR with DKA. FTR1and GRP78 plays a crucial role in MCR patients infected with SARS CoV-2. Large cohorts of genomic studies will be required to enlighten the novel pathways of pathophysiology and their target genes for efficient drug design.