The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus–host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.

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S evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic human coronavirus to cross the species barrier into the human population during the past 20 years (1-3). SARS-CoV-2 infection is associated with coronavirus disease (COVID-19), which is characterized by severe respiratory distress, fever, and cough and high rates of mortality, especially in older persons and those with underlying health conditions (3). The World Health Organization (WHO) declared SARS-CoV-2 a pandemic on March 11, 2020 (4), and by April 8, a total of 1,447,466 confirmed cases and 83,471 deaths from SARS-CoV-2 had been reported worldwide (5). Human-to-human transmission of SARS-CoV-2 is efficient, and infected persons can transmit the virus even when they have no, or only mild, symptoms (3). Because no antiviral drugs or vaccines are available, virus containment and prevention of infection are the current highest priorities. To limit virus spread, effective hand hygiene is crucial. Therefore, easily available but efficient disinfectants are needed. WHO's guidelines for hand hygiene in healthcare suggest 2 alcohol-based formulations for hand sanitization to reduce the infectivity and spread of pathogens (6). WHO's recommendations are based on fastacting, broad-spectrum microbicidal activity, along with accessibility and safety. The original WHO formulations failed to meet the efficacy requirements of European Norm 1500 in previous tests (7). However, Suchomel et al. (8) suggested modified versions with increased concentrations of ethanol: 80% (wt/ wt) (85.5% [vol/vol]; formulation I), or isopropanol, 75% (wt/wt) (81.3% [vol/vol]; formulations II). Later, they complemented these by reducing the glycerol concentrations (9). We previously showed that these modified WHO formulations were able to inactivate severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV; 10), which are related to SARS-CoV-2. Current recommendations to inactivate SARS-CoV-2 were translated from findings of other coronaviruses (11). To evaluate whether these alcohol-based disinfectants also effectively inactivate SARS-CoV-2, we tested different concentrations of the original and modified WHO formulations I and II (6,9), ethanol, and 2-propanol for virucidal activity.

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Since its emergence in December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally and become a major public health burden. Despite its close phylogenetic relationship to SARS-CoV, SARS-CoV-2 exhibits increased human-to-human transmission dynamics, likely due to efficient early replication in the upper respiratory epithelium of infected individuals. Since different temperatures encountered in the human upper and lower respiratory tract (37°C and 33°C, respectively) have been shown to affect the replication kinetics of several respiratory viruses, as well as host immune response dynamics, we investigated the impact of temperatures during SARS-CoV-2 and SARS-CoV infection using the primary human airway epithelial cell culture model. SARS-CoV-2, in contrast to SARS-CoV, replicated to higher titers when infections were performed at 33°C rather than 37°C. Although both viruses were highly sensitive to type I and type III interferon pretreatment, a detailed time-resolved transcriptome analysis revealed temperature-dependent interferon and pro-inflammatory responses specifically induced by SARS-CoV or SARS-CoV-2, which amplitude was inversely proportional to their replication efficiencies at 33°C or 37°C. These data provide crucial insight on pivotal virus–host interaction dynamics and are in line with characteristic clinical features of SARS-CoV-2 and SARS-CoV, as well as their respective transmission efficiencies.