Since SARS-CoV-2 is more phylogenetically related to SARS-CoV than MERS-CoV,22 we further detected the cross-reactivity of SARS-CoV RBD-specific antibodies with SARS-CoV-2 RBD and cross-neutralizing activity of SARS-CoV RBD-specific antibodies against pseudotyped SARS-CoV-2. First, we performed an ELISA to detect the cross-reactivity of SARS-CoV RBD-immunized mouse sera with SARS-CoV-2 RBD. The results showed that SARS-CoV-2 RBD reacted strongly with anti-SARS-CoV RBD IgG with antibody titer of 1:2.4 × 104 (Fig. 4d), but it did not react with anti-MERS-CoV RBD IgG (Fig. 4e). As expected, SARS-CoV RBD reacted strongly with anti-SARS-CoV RBD IgG (antibody titer: 1:1.4 × 105) (Fig. 4d), but not with anti-MERS-CoV RBD IgG (Fig. 4e). MERS-CoV RBD did not react with anti-SARS-CoV RBD IgG (Fig. 4d), but instead reacted with anti-MERS-CoV RBD IgG (antibody titer: 1:1.3 × 105) (Fig. 4e). Second, we performed a pseudovirus neutralization assay to detect the cross-neutralizing activity of SARS-CoV RBD-immunized mouse sera against SARS-CoV-2 pseudovirus infection. Results revealed that SARS-CoV RBD-specific antisera could neutralize SARS-CoV-2 pseudovirus infection with a neutralizing antibody titer of 1:323, while these antisera could neutralize SARS-CoV pseudovirus infection with higher neutralizing antibody titer (1:1.2 × 104) (Fig. 4f). MERS-CoV RBD-inducing mouse sera only neutralized MERS-CoV pseudovirus infection in hDPP4-expressing cells with a neutralizing antibody titer of 1:4 × 104 (Fig. 4g), but failed to neutralize infection by either SARS-CoV-2 pseudovirus or SARS-CoV pseudovirus (Fig. 4f). These data suggest that SARS-CoV RBD-specific antibodies can cross-react with SARS-CoV-2 RBD and cross-neutralize SARS-CoV-2 pseudovirus infection.