SARS-CoV-2 ORF7b: is a bat virus protein homologue a major cause of COVID-19 symptoms?

ORF7b is an accessory protein of SARS-CoV-2, the virus behind the COVID-19 pandemic. Using cell-free synthesized ORF7b, we experimentally show that ORF7b assembles into stable multimers. The ORF7b sequence shows a transmembrane segment, which multimerizes through a leucine zipper. We hypothesize that ORF7b has the potential to interfere with important cellular processes that involve leucine-zipper formation, and present two particularly striking examples. First, leucine zippers are central in heart rhythm regulation through multimerization of phospholamban in cardiomyocytes. Second, epithelial cell-cell adhesion relies on E-cadherins, which dimerize using a transmembrane leucine zipper. Most common symptoms of SARS-CoV-2 infection, including heart arrythmias, odor loss, impaired oxygen uptake and intestinal problems, up to multiorgan failure, can be rationalized by a possible interference of ORF7b with the functions of these proteins. We ask whether this is pure coincidence, or whether our observations point to disruption by ORF7b of vital processes in COVID-19.