Avian infectious bronchitis virus was the first CoV isolated in 1930. Different CoVs were subsequently isolated in infected rodents and domestic animals, including mouse, pig, cow, turkey, cats, and dogs. CoVs were once believed not to cause human disease, but this was changed after the successful isolation of HCoV strain B814 from the clinical specimen of patients with common cold by serial passage of inoculum in tracheal organ culture in 1962 [2]. In the 1960s, several novel HCoVs were described but no further characterization was performed in most cases [3,4]. 229E and OC43 were known as causative agents of the common cold and upper respiratory tract infection, accounting for up to 30% of cases with common cold [4]. 229E is a prototype strain isolated using tracheal organ culture. OC43 was isolated from organ culture and subsequent serial passage in the brain of suckling mice. The clinical features of 229E and OC43 infection were characterized in human volunteer study [4]. In most cases, natural infection with HCoVs results in mild common cold-like symptoms. Severe lower respiratory tract infection develops only in immunocompromised patients [5]. Apart from a respiratory infection, 229E and OC43 were suspected to infect the central nervous system (CNS) as mRNA and CoV-like particles were detected in CNS samples of patients with multiple sclerosis. This claim was further supported by the susceptibility of human neural primary culture to 229E and OC43 [6]. However, the influence of 229E and OC43 on the development and progression of multiple sclerosis awaits further investigations.