The SARS-CoV-2 pandemic has marked the third zoonotic introduction of a highly pathogenic coronavirus into humans. While SARS-CoV and MERS-CoV raised awareness of the need for therapeutic interventions, no effective treatments are available for SARS-CoV-2. Understanding the molecular mechanisms of coronavirus infections is crucial for developing interventions. This review summarizes current knowledge of SARS-CoV-2 infection through its intracellular life cycle and relates it to coronavirus biology. The similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness against coronavirus infections. Coronaviruses are enveloped positive-sense single-stranded RNA viruses that infect humans, other mammals, and birds. They are divided into four genera: alphacoronaviruses, betacoronaviruses, gammacoronaviruses, and deltacoronaviruses. Alphacoronaviruses and betacoronaviruses infect mammals, while gammacoronaviruses and deltacoronaviruses have a broader host range. Human and animal coronavirus infections mainly result in respiratory and enteric diseases. Human coronaviruses, such as HCoV-229E and HCoV-OC43, cause mild respiratory infections. In contrast, SARS-CoV, MERS-CoV, and SARS-CoV-2 are highly pathogenic. The initial steps of coronavirus infection involve the binding of the S protein to cellular entry receptors, such as ACE2. The expression and distribution of these receptors influence viral tropism and pathogenicity. During the intracellular life cycle, coronaviruses express and replicate their genomic RNA to produce full-length copies that are incorporated into viral particles. The viral genome contains cis-acting secondary RNA structures essential for RNA synthesis. The S protein is divided into two parts, S1 and S2, with S1 containing the receptor-binding domain (RBD) and S2 mediating membrane fusion. The SARS-CoV-2 S protein has a polybasic cleavage site that allows efficient cleavage by furin, enhancing infection and potentially contributing to zoonotic potential. The entry of SARS-CoV-2 into host cells involves receptor binding and proteolytic cleavage of the S protein by host cell-derived proteases. TMPRSS2 is essential for SARS-CoV-2 entry. The SARS-CoV-2 S protein has a high affinity for ACE2, but the overall S protein affinity may be lower than that of SARS-CoV. The SARS-CoV-2 S protein also has a unique cleavage site that may contribute to its increased transmissibility. The replication cycle of coronaviruses involves the production of subgenomic mRNAs (sg mRNAs) that are translated into structural and accessory proteins. The viral replication complex (RTC) is essential for RNA synthesis andThe SARS-CoV-2 pandemic has marked the third zoonotic introduction of a highly pathogenic coronavirus into humans. While SARS-CoV and MERS-CoV raised awareness of the need for therapeutic interventions, no effective treatments are available for SARS-CoV-2. Understanding the molecular mechanisms of coronavirus infections is crucial for developing interventions. This review summarizes current knowledge of SARS-CoV-2 infection through its intracellular life cycle and relates it to coronavirus biology. The similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness against coronavirus infections. Coronaviruses are enveloped positive-sense single-stranded RNA viruses that infect humans, other mammals, and birds. They are divided into four genera: alphacoronaviruses, betacoronaviruses, gammacoronaviruses, and deltacoronaviruses. Alphacoronaviruses and betacoronaviruses infect mammals, while gammacoronaviruses and deltacoronaviruses have a broader host range. Human and animal coronavirus infections mainly result in respiratory and enteric diseases. Human coronaviruses, such as HCoV-229E and HCoV-OC43, cause mild respiratory infections. In contrast, SARS-CoV, MERS-CoV, and SARS-CoV-2 are highly pathogenic. The initial steps of coronavirus infection involve the binding of the S protein to cellular entry receptors, such as ACE2. The expression and distribution of these receptors influence viral tropism and pathogenicity. During the intracellular life cycle, coronaviruses express and replicate their genomic RNA to produce full-length copies that are incorporated into viral particles. The viral genome contains cis-acting secondary RNA structures essential for RNA synthesis. The S protein is divided into two parts, S1 and S2, with S1 containing the receptor-binding domain (RBD) and S2 mediating membrane fusion. The SARS-CoV-2 S protein has a polybasic cleavage site that allows efficient cleavage by furin, enhancing infection and potentially contributing to zoonotic potential. The entry of SARS-CoV-2 into host cells involves receptor binding and proteolytic cleavage of the S protein by host cell-derived proteases. TMPRSS2 is essential for SARS-CoV-2 entry. The SARS-CoV-2 S protein has a high affinity for ACE2, but the overall S protein affinity may be lower than that of SARS-CoV. The SARS-CoV-2 S protein also has a unique cleavage site that may contribute to its increased transmissibility. The replication cycle of coronaviruses involves the production of subgenomic mRNAs (sg mRNAs) that are translated into structural and accessory proteins. The viral replication complex (RTC) is essential for RNA synthesis and