ORF8

ORF8 is one of the most variable among SARS-CoV-1. Remarkably, 29 nucleotide N-terminal sequence has gone under gradual deletion during SARS-CoV-1 spread in humans. Early tests showed a decrease in viral replication by up to 23-fold when this sequence was removed. SARS-CoV-2 ORF8 is 127 amino acids long and 45% identical to SARS-CoV-1 ORF8b.

Narrative

SARS-CoV-2 ORF8 is most similar to sequences from Bat-SARS-like coronavirus and a bat coronavirus RaTG13 (D. Hu et al. 2018). Remarkably, removal of a N-terminal 29 nucleotide sequence from SARS-CoV-1 ORF8 in early tests showed a decrease in viral replication by up to 23-fold (Muth et al. 2018). This sequence was observed to be removed from the virus in human cases later in the outbreak along with additional and different mutations of ORF8 (Chiu et al. 2005; Chinese SARS Molecular Epidemiology Consortium 2004a). The exact purpose of this mutation and ORF8’s function in regards to viral benefit within human hosts remains unknown. With the deletion, SARS-CoV-1 encodes ORF8a and ORF8b, while SARS-CoV-2 ORF8 is intact (Guan et al. 2003; Chinese SARS Molecular Epidemiology Consortium 2004b; Lau et al. 2005; D. E. Gordon et al. 2020). SARS-CoV-2 ORF8 is 127 a.a. long and 45% identical to SARS-CoV-1 ORF8b.