Abstract: The invention provides an isolated essentially mammalian positive-sense single stranded RNA virus classifiable as belonging to the Order: Nidovirales; Family: Coronaviridae; Subfamily: Coronavirinae; Genus: Betacoronavirus; and non-Lineage A, non-Lineage B or non-Lineage D, human betacoronavirus. The invention also provides a human virus having a receptor binding domain (RBD) capable of binding to a dipeptidyl peptidase 4. The invention also provides diagnostic means and methods, prophylactic means and methods and therapeutic means and methods to be employed in the diagnosis, prevention and/or treatment of disease, in particular of respiratory disease, in particular of mammals, more in particular in humans.