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Virus-Cell InteractionsReceptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS CoronavirusThe recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of...
GemMetabolic Syndrome and Viral Pathogenesis: Lessons from Influenza and CoronavirusesMetabolic syndrome increases the risk of severe disease due to viral infection. Yet few studies have assessed the pathogenesis of respiratory viruses in high-risk populations. Here, we summarize how metabolic dysregulation impairs immune responses, and we define the role of metabolism during influenza virus and coronavirus infections. We also discuss the use of various in vitro, in vivo, and ex vivo models to...
Virus-Cell InteractionsMolecular Mechanism for Antibody-Dependent Enhancement of Coronavirus EntryAntibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into...
Genetic Diversity and EvolutionHuman Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the...
MinireviewCOVID-19 Vaccines: “Warp Speed” Needs Mind Melds, Not Warped MindsIn this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of humans and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what...
Cellular Response to InfectionType I and Type III Interferons Restrict SARS-CoV-2 Infection of Human Airway Epithelial CulturesThe current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. Our...
Virus-Cell Interactions | SpotlightTrypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus InfectionOverall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously...
Structure and Assembly | SpotlightComparison of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals, and Putative Intermediate HostsSARS-CoV-2 is threatening people worldwide, and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear, and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the...
