Since January 2020, Elsevier has created a free COVID-19 resource center with English and Mandarin information on the novel coronavirus. The center is hosted on Elsevier Connect, a public news and information website. Elsevier grants permission to make all its COVID-19-related research immediately available in PubMed Central and other public repositories for unrestricted reuse and analysis. The article discusses insights into SARS-CoV-2 genome, structure, evolution, pathogenesis, and therapies through a structural genomics approach. It highlights differences in genomic, proteomic, pathogenesis, and therapeutic strategies between SARS-CoV-2 and SARS-CoV and MERS-CoV. Sequence analysis of potential drug target proteins in SARS-CoV-2 is compared with SARS-CoV and MERS-CoV. Mutations in coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 are analyzed. A detailed structural analysis of drug target proteins is performed to understand pathogenesis mechanisms, structure-function relationships, and structure-guided therapeutic approaches. Cytokine profiling and inflammatory signaling differ in SARS-CoV-2 infection. Possible therapies and their mechanisms are highlighted, suggesting that minimal genome sequence variation in SARS-CoV-2 may lead to drastic changes in target protein structures, making drugs ineffective. The article explores the molecular basis of SARS-CoV-2 pathogenesis, including host entry mechanisms, viral replication, and the role of key enzymes like 3CLpro, PLpro, and RdRp. These enzymes are crucial for viral survival, replication, and transmission, making them potential drug targets. The SARS-CoV-2 genome is a single-stranded positive-sense RNA, with high sequence similarity to SARS-CoV and MERS-CoV. The genome contains 11 protein-coding genes and 12 expressed proteins, with a structure similar to SARS-CoV and MERS-CoV. The genome is organized in a linear topology, with a high GC content and sequence identity to other CoVs. The article discusses non-structural proteins (NSPs) involved in viral replication and assembly, their roles in pathogenesis, and their structural characteristics. Potential drug targets include the spike glycoprotein (S), envelope protein (E), membrane protein (M), nucleoprotein (N), and replicase polyprotein. The S protein is a key target due to its role in host cell entry via ACE2 receptor. Structural analysis of the S protein shows significant differences between SARS-CoV-2 and SARS-CoV, affecting antibody efficacy. The E protein is involved in viral morphogenesis and assembly, while the M protein plays a major role in RNA packaging. The N protein is crucial for viral RNA packaging and is a potential drug target. The article also discusses inflammatory pathways and cytokine responses during SARS-CoV-2 infection, highlighting the role of the innate immuneSince January 2020, Elsevier has created a free COVID-19 resource center with English and Mandarin information on the novel coronavirus. The center is hosted on Elsevier Connect, a public news and information website. Elsevier grants permission to make all its COVID-19-related research immediately available in PubMed Central and other public repositories for unrestricted reuse and analysis. The article discusses insights into SARS-CoV-2 genome, structure, evolution, pathogenesis, and therapies through a structural genomics approach. It highlights differences in genomic, proteomic, pathogenesis, and therapeutic strategies between SARS-CoV-2 and SARS-CoV and MERS-CoV. Sequence analysis of potential drug target proteins in SARS-CoV-2 is compared with SARS-CoV and MERS-CoV. Mutations in coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 are analyzed. A detailed structural analysis of drug target proteins is performed to understand pathogenesis mechanisms, structure-function relationships, and structure-guided therapeutic approaches. Cytokine profiling and inflammatory signaling differ in SARS-CoV-2 infection. Possible therapies and their mechanisms are highlighted, suggesting that minimal genome sequence variation in SARS-CoV-2 may lead to drastic changes in target protein structures, making drugs ineffective. The article explores the molecular basis of SARS-CoV-2 pathogenesis, including host entry mechanisms, viral replication, and the role of key enzymes like 3CLpro, PLpro, and RdRp. These enzymes are crucial for viral survival, replication, and transmission, making them potential drug targets. The SARS-CoV-2 genome is a single-stranded positive-sense RNA, with high sequence similarity to SARS-CoV and MERS-CoV. The genome contains 11 protein-coding genes and 12 expressed proteins, with a structure similar to SARS-CoV and MERS-CoV. The genome is organized in a linear topology, with a high GC content and sequence identity to other CoVs. The article discusses non-structural proteins (NSPs) involved in viral replication and assembly, their roles in pathogenesis, and their structural characteristics. Potential drug targets include the spike glycoprotein (S), envelope protein (E), membrane protein (M), nucleoprotein (N), and replicase polyprotein. The S protein is a key target due to its role in host cell entry via ACE2 receptor. Structural analysis of the S protein shows significant differences between SARS-CoV-2 and SARS-CoV, affecting antibody efficacy. The E protein is involved in viral morphogenesis and assembly, while the M protein plays a major role in RNA packaging. The N protein is crucial for viral RNA packaging and is a potential drug target. The article also discusses inflammatory pathways and cytokine responses during SARS-CoV-2 infection, highlighting the role of the innate immune