Nonstructural proteins of human coronavirus NL63

In March 2004, a new human coronavirus was identified in The Netherlands. Named HCoV-NL63, it was found to cause acute respiratory disease in both children below the age of 1 and immunocompromised adults.1 HCoV-NL63 belongs to the first of the three groups the coronaviruses have been subdivided into. Its plus-strand RNA genome consists of 27,553 nucleotides and a poly-A tail. At variance with typical group 1 coronaviruses, HCoV-NL63 has an additional 179-amino acid residue domain in the Sprotein and only one open reading frame (ORF) instead of two between the S and the E gene.1 Very recently, it was found that the HCoV-NL63 spike-protein binds to the SARSCoV receptor angiotensin-converting enzyme 2 (ACE-2) but not to CD13 as other group I coronaviruses.2 The genome of all known coronaviruses contains two ORFs that encode nonstructural proteins, and these are followed by the genes encoding the four structural proteins. Nonstructural proteins play an essential role in the replication and transcription of the virus genome as well as in polyprotein processing. Elucidating their structures and functions will pave the way for anticoronaviral drug discovery.3,4