Targeting cell surface GRP78 for the treatment of mucormycosis: potential and promising therapeutic approach

Endoplasmic reticulum transmembrane signal transducers generate glucose-regulated protein (GRP78) in response to ER stress. Evidence suggests that the endothelial and epithelial cell surface 78 kDa, GRP78 is necessary for the pathogenesis of some infections. Several anti-GRP78 drugs have been identified and evaluated as potential antiviral therapies. Thus, the suppression of GRP78 is likely to result in multiple promising outcomes in infection management. Mucormycosis is a severe and invasive infection caused by fungi belonging to the order Mucorales. These fungi employ GRP78 receptors on the surfaces of endothelial and epithelial cells to facilitate host cell invasion. The spore coat protein homologous (CotH) cell surface antigens, CotH3 of Mucorales in particular, plays a crucial role in the attachment of fungi to the host cell GRP78. This review article aimed to evaluate the available evidence on the therapeutic potential of targeting GRP78 in the management of mucormycosis. Based on data from in-silico, in-vitro, and animal studies that strongly support the use of csGRP78-targeted inhibitors in anticancer therapies, targeting csGRP78 with GRP78 inhibitors would be a promising strategy for the effective management of mucormycosis.