Swine acute diarrhea syndrome coronavirus-related viruses from bats show potential interspecies infection

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a bat-originated virus causing severe diseases in piglets. Since the 2016 outbreak, diverse SADS-related CoVs (SADSr-CoVs) have been detected in Rhinolophus bats in China and Southeast Asia, but their potential interspecies infection and pathogenicity remain unknown. Herein, we sequenced the spike (S) genes of bat SADSr-CoVs and classified them into four genotypes. We constructed an infectious SADS-CoV cDNA clone (rSADS-CoV) and nine recombinant viruses by replacing the SADS-CoV S gene with that of bat SADSr-CoVs. Recombinant SADSr-CoVs could replicate efficiently in respiratory and intestinal cell lines and human- and swine-derived organoids and caused varying tissue damage and mortality in suckling mice. These viruses can be classified into at least five serotypes based on cross-neutralization assays. Our findings highlight the potential risk of interspecies infection and provide important information for future surveillance of these bat viruses.IMPORTANCEOver the last 20 years, several bat-originated coronaviruses (CoVs), including SARS-CoV, MERS-CoV, and , have caused millions of deaths and severely disrupted global health systems, highlighting the need to investigate bat CoV spillover risks. SADS-CoV, another bat-derived CoV highly pathogenic to piglets, threatens the swine industry and exhibits broad cell tropism, underscoring the need to study these highly diverse viruses with potential for interspecies infection and pathogenicity. As part of our effort to understand these viruses, we developed a framework to characterize them in cell lines and organoids derived from swine and humans, as well as in suckling mice. Additionally, we performed serum cross-neutralization to classify bat SADSr-CoV serotypes, which could guide the development of broad-spectrum vaccines against SADSr-CoVs.