Elsevier established a free COVID-19 resource center in January 2020, offering English and Mandarin information on the virus. The center hosts research on the SARS-CoV-2 virus, allowing unrestricted reuse in public repositories. A study using reverse genetics generated SARS-CoV-2 infectious cDNA clones and reporter viruses to examine infection gradients in the respiratory tract. The research found that SARS-CoV-2 infectivity decreases from the nasal region to the alveolar region, with ciliated airway cells and type 2 pneumocytes as primary targets. The study also showed limited cross-neutralization between SARS-CoV and SARS-CoV-2. ACE2 expression was highest in the nasal region, decreasing in the lower respiratory tract, aligning with the infection gradient. Autopsy studies confirmed SARS-CoV-2 infection in ciliated and type 2 pneumocytes in the airway and alveolar regions. The findings suggest nasal susceptibility and subsequent aspiration of the virus into the lungs. The study provides tools for investigating virus-host interactions, immunity, and pathogenesis. The research also evaluated the role of proteases like TMPRSS2 and furin in SARS-CoV-2 replication. Neutralization assays showed limited cross-neutralization between SARS-CoV and SARS-CoV-2. The study used RNA in situ hybridization to map ACE2 and TMPRSS2 expression in the respiratory tract, revealing higher ACE2 expression in the nasal region. The study also found that pre-existing pulmonary diseases like cystic fibrosis may alter ACE2 and TMPRSS2 expression, affecting SARS-CoV-2 susceptibility. The research highlights the importance of nasal infection and aspiration in SARS-CoV-2 pathogenesis. The study provides insights into the variability of SARS-CoV-2 infection in different respiratory regions and the role of ACE2 and TMPRSS2 in viral entry. The findings suggest that nasal infection is a key initial site for SARS-CoV-2, with subsequent aspiration into the lungs. The study also discusses the role of environmental factors in nasal infectivity and the potential for aspiration of virus into the lower respiratory tract. The research contributes to understanding the mechanisms of SARS-CoV-2 infection and the development of therapeutic strategies. The study provides a SARS-CoV-2 infectious cDNA clone and tools for neutralization assays, aiding in the study of virus-host interactions and vaccine development. The findings have implications for understanding the pathogenesis of SARS-CoV-2 and the development of treatments for severe cases. The study also highlights the importance of ACE2 expression in the respiratory tract and its role in SARS-CoV-2 infection. The research provides a foundation for future studies on SARS-CoV-2 and its interactions with the human respiratory system.Elsevier established a free COVID-19 resource center in January 2020, offering English and Mandarin information on the virus. The center hosts research on the SARS-CoV-2 virus, allowing unrestricted reuse in public repositories. A study using reverse genetics generated SARS-CoV-2 infectious cDNA clones and reporter viruses to examine infection gradients in the respiratory tract. The research found that SARS-CoV-2 infectivity decreases from the nasal region to the alveolar region, with ciliated airway cells and type 2 pneumocytes as primary targets. The study also showed limited cross-neutralization between SARS-CoV and SARS-CoV-2. ACE2 expression was highest in the nasal region, decreasing in the lower respiratory tract, aligning with the infection gradient. Autopsy studies confirmed SARS-CoV-2 infection in ciliated and type 2 pneumocytes in the airway and alveolar regions. The findings suggest nasal susceptibility and subsequent aspiration of the virus into the lungs. The study provides tools for investigating virus-host interactions, immunity, and pathogenesis. The research also evaluated the role of proteases like TMPRSS2 and furin in SARS-CoV-2 replication. Neutralization assays showed limited cross-neutralization between SARS-CoV and SARS-CoV-2. The study used RNA in situ hybridization to map ACE2 and TMPRSS2 expression in the respiratory tract, revealing higher ACE2 expression in the nasal region. The study also found that pre-existing pulmonary diseases like cystic fibrosis may alter ACE2 and TMPRSS2 expression, affecting SARS-CoV-2 susceptibility. The research highlights the importance of nasal infection and aspiration in SARS-CoV-2 pathogenesis. The study provides insights into the variability of SARS-CoV-2 infection in different respiratory regions and the role of ACE2 and TMPRSS2 in viral entry. The findings suggest that nasal infection is a key initial site for SARS-CoV-2, with subsequent aspiration into the lungs. The study also discusses the role of environmental factors in nasal infectivity and the potential for aspiration of virus into the lower respiratory tract. The research contributes to understanding the mechanisms of SARS-CoV-2 infection and the development of therapeutic strategies. The study provides a SARS-CoV-2 infectious cDNA clone and tools for neutralization assays, aiding in the study of virus-host interactions and vaccine development. The findings have implications for understanding the pathogenesis of SARS-CoV-2 and the development of treatments for severe cases. The study also highlights the importance of ACE2 expression in the respiratory tract and its role in SARS-CoV-2 infection. The research provides a foundation for future studies on SARS-CoV-2 and its interactions with the human respiratory system.