Coronaviruses, a family of positive-sense RNA viruses, have been known for decades but gained notoriety in 2003 with the SARS outbreak. This review discusses recent advances in understanding coronavirus replication, host interactions, and pathogenesis. Coronaviruses are divided into three groups based on serological and genetic analyses. They replicate using a large ORF1a/b polyprotein, which is cleaved into non-structural proteins, and a smaller ORF1ab polyprotein, which encodes structural proteins. The S protein binds to host receptors like ACE2, facilitating entry into cells. The E protein is involved in virus morphogenesis and budding, and its absence inhibits virus release. Coronaviruses also encode accessory proteins that may play roles in replication in natural hosts. Coronaviruses can cause mild to severe respiratory and systemic diseases. SARS-CoV, for example, caused severe respiratory disease with high mortality. Other coronaviruses, such as HCoV-NL63, cause mild upper respiratory tract infections. Coronaviruses have the ability to cross species barriers, as seen with SARS-CoV spreading from bats to civets and humans. This cross-species transmission is facilitated by mutations in the receptor-binding domain of the S protein, allowing efficient infection of new hosts. The immune response plays a critical role in coronavirus infections. Host efforts to clear the virus can lead to immunopathological disease, such as demyelination in the central nervous system. Coronaviruses have evolved strategies to evade the innate immune response, including inhibiting interferon production and signaling. These mechanisms help the virus replicate and spread while avoiding detection by the immune system. Animal models, such as transgenic mice expressing human ACE2, have been developed to study coronavirus infections and test vaccines and therapies. These models help understand the pathogenesis of coronaviruses and the role of the immune response in disease severity. Future research aims to better understand coronavirus interactions with the immune system, develop effective antiviral therapies, and create safe, attenuated vaccines. The study of coronavirus replication and pathogenesis continues to provide insights into the mechanisms of these viruses and their potential to cause disease in new hosts.Coronaviruses, a family of positive-sense RNA viruses, have been known for decades but gained notoriety in 2003 with the SARS outbreak. This review discusses recent advances in understanding coronavirus replication, host interactions, and pathogenesis. Coronaviruses are divided into three groups based on serological and genetic analyses. They replicate using a large ORF1a/b polyprotein, which is cleaved into non-structural proteins, and a smaller ORF1ab polyprotein, which encodes structural proteins. The S protein binds to host receptors like ACE2, facilitating entry into cells. The E protein is involved in virus morphogenesis and budding, and its absence inhibits virus release. Coronaviruses also encode accessory proteins that may play roles in replication in natural hosts. Coronaviruses can cause mild to severe respiratory and systemic diseases. SARS-CoV, for example, caused severe respiratory disease with high mortality. Other coronaviruses, such as HCoV-NL63, cause mild upper respiratory tract infections. Coronaviruses have the ability to cross species barriers, as seen with SARS-CoV spreading from bats to civets and humans. This cross-species transmission is facilitated by mutations in the receptor-binding domain of the S protein, allowing efficient infection of new hosts. The immune response plays a critical role in coronavirus infections. Host efforts to clear the virus can lead to immunopathological disease, such as demyelination in the central nervous system. Coronaviruses have evolved strategies to evade the innate immune response, including inhibiting interferon production and signaling. These mechanisms help the virus replicate and spread while avoiding detection by the immune system. Animal models, such as transgenic mice expressing human ACE2, have been developed to study coronavirus infections and test vaccines and therapies. These models help understand the pathogenesis of coronaviruses and the role of the immune response in disease severity. Future research aims to better understand coronavirus interactions with the immune system, develop effective antiviral therapies, and create safe, attenuated vaccines. The study of coronavirus replication and pathogenesis continues to provide insights into the mechanisms of these viruses and their potential to cause disease in new hosts.