Iron and glucose-regulated protein 78: fundamental components in the coinfection of Rhizopus oryzae and SARS-CoV-2

Abstract

The viral outbreak of severe acute respiratory syndrome coronavirus 2 emerged in China by the end of 2019 and was declared a global pandemic in early 2020. Along with the growing number of fatalities and lack of specific treatment at the time, the increasing incidence of mucormycosis worried World health agencies, as it ran the risk of more threatening outcomes for COVID-19 patients. In this context, this review aims to assemble case reports of COVID-19 associated mucormycosis and discuss virulence and host factors involved in the progress of these infections – key aspects that might unveil biological targets and pharmacological approaches to treat these infections. Recently, elevated serum iron levels during SARS-CoV-2 infection have been reported in the literature. Besides being a clinical characteristic of diabetic patients, iron overload is described as a risk factor for Rhizopus oryzae infection. Furthermore, the increased expression of human heat-shock protein GRP78 during iron overload and coronavirus infection displays a crucial role as a mediator in Mucorales invasion. These remarkable mechanisms might explain the high incidence of mucormycosis in COVID-19 patients with diabetes and, therefore, suggest regulation of GRP78 expression, management of glycemia and glucocorticoid treatment as potential therapeutic targets of this severe coinfection.