Fig. 5. Variable regions in different SARS-CoV and bat SARSr-CoV isolates.

Variability and thus species adaptation majorly affect three severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-related coronavirus (SARSr-CoV) proteins: the spike protein (S) (both the S1 amino-terminal domain (S1-NTD) and the S1 receptor-binding domain (S1-RBD) show variability), ORF3 (3a and 3b) and ORF8 (8a and b). SARS-CoV GD02 and hTor02 represent strains that were isolated from patients during the early, and middle or late phase of the SARS epidemic in 2002–2003, respectively; SARS-CoV CZ3 is a representative of strains isolated from civets in 2003 and 2004 (refs^42,62). All bat SARSr-CoVs, except HKU3 and Rp3, were discovered in Yunnan province during 2011–2015. On the basis of deletions in the RBD, bat SARSr-CoVs can be divided into two clades. Those without a deletion and thus an identical size in S1 to SARS-CoV can be further divided into four genotypes: genotype 1, represented by WIV16, is highly similar to SARS-CoV in both the NTD and the RBD; genotype 2, represented by WIV1, differs in NTD from SARS-CoV; genotype 3, represented by Rs4231, differs in RBD from SARS-CoV; and genotype 4, represented by SHC014 and Rs4084, differs in both NTD and RBD from SARS-CoV²⁰. The differences in S influence species-specific receptor binding, whereas differences in the accessory proteins, including potentially the newly discovered ORFX (X), mainly affect immune responses and viral immune evasion. Adapted from ref.²⁰, CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).