As a major surface glycoprotein of enveloped viruses, the virus spike protein is a primary target for vaccines and anti-viral treatments. Current vaccines aiming at controlling the COVID-19 pandemic are mostly directed against the SARS-CoV-2 spike protein. To promote virus entry and facilitate immune evasion, spikes must be dynamic. Interactions with host receptors and coreceptors trigger a cascade of conformational changes/structural rearrangements in spikes, which bring virus and host membranes in proximity for membrane fusion required for virus entry. Spike-mediated viral membrane fusion is a dynamic, multi-step process, and understanding the structure–function-dynamics paradigm of virus spikes is essential to elucidate viral membrane fusion, with the ultimate goal of interventions. However, our understanding of this process primarily relies on individual structural snapshots of endpoints. How these endpoints are connected in a time-resolved manner, and the order and frequency of conformational events underlying virus entry, remain largely elusive. Single-molecule Förster resonance energy transfer (smFRET) has provided a powerful platform to connect structure–function in motion, revealing dynamic aspects of spikes for several viruses: SARS-CoV-2, HIV-1, influenza, and Ebola. This review focuses on how smFRET imaging has advanced our understanding of virus spikes’ dynamic nature, receptor-binding events, and mechanism of antibody neutralization, thereby informing therapeutic interventions.
【저자키워드】 SARS-CoV-2, HIV-1, virus entry, conformational dynamics, virus–host interactions, Spike proteins, Viral membrane fusion, single-molecule imaging, Förster resonance energy transfer (FRET), influenza and Ebola, 【초록키워드】 viruses, Vaccine, spike, Influenza, COVID-19 pandemic, virus, Spike protein, Anti-viral, Surface glycoprotein, immune evasion, Ebola, membrane fusion, platform, mechanism, Antibody neutralization, Frequency, endpoints, energy transfer, Endpoint, spikes, viral membrane, host receptor, therapeutic interventions, cascade, virus spike protein, Virus spike, event, current, required, events, provided, facilitate, promote, conformational, host membrane, the SARS-CoV-2, 【제목키워드】 imaging,