Monoclonal antibodies (MAbs) may be helpful in the intervention of disease in CoV-exposed individuals. Patients recovering from SARS showed robust neutralizing antibodies against this CoV infection (164). A set of MAbs aimed at the MERS-CoV S protein-specific domains, comprising six specific epitope groups interacting with receptor-binding, membrane fusion, and sialic acid-binding sites, make up crucial entry tasks of S protein (198, 199). Passive immunization employing weaker and strongly neutralizing antibodies provided considerable protection in mice against a MERS-CoV lethal challenge. Such antibodies may play a crucial role in enhancing protective humoral responses against the emerging CoVs by aiming appropriate epitopes and functions of the S protein. The cross-neutralization ability of SARS-CoV RBD-specific neutralizing MAbs considerably relies on the resemblance between their RBDs; therefore, SARS-CoV RBD-specific antibodies could cross-neutralized SL CoVs, i.e., bat-SL-CoV strain WIV1 (RBD with eight amino acid differences from SARS-CoV) but not bat-SL-CoV strain SHC014 (24 amino acid differences) (200).