FRETing over SARS-CoV-2: Conformational Dynamics of the Spike Glycoprotein

Serrão, Vitor Hugo Balasco; Lee, Jeffrey E.

doi:10.1016/j.chom.2020.11.008

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…Microsecond-scale molecular dynamics simulations revealed large conformational changes in 𝑆1 and elucidated the impact of glycans and 𝑅𝐵𝐷-distal mutations in the closed/open transition pathways (25)(26)(27)(28). Experimentally, single-molecule FRET (smFRET) monitored real-time dynamics of labeled 𝑅𝐵𝐷 in 𝑆 trimers, revealing subsecond transition times between up to four conformations attributed to states in which one or multiple 𝑅𝐵𝐷s are open (29)(30)(31)(32). Finally, high-speed atomic force microscopy (HS-AFM) imaging monitored the dynamics of these transitions (17,33,34).…”

Section: Main Textmentioning

confidence: 99%

Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection

Saha,

Fernanadez,

Sumbul

et al. 2024

Preprint

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The first step of SARS-CoV-2 infection involves the interaction between the trimeric viral spike protein (𝑆) and the host angiotensin-converting enzyme 2 (𝐴𝐶𝐸2). The receptor binding domain (𝑅𝐵𝐷) of 𝑆 adopts two conformations: open and closed, respectively, accessible and inaccessible to 𝐴𝐶𝐸2. Therefore, 𝑅𝐵𝐷 motions are suspected to affect 𝐴𝐶𝐸2 binding; yet a quantitative description of the underlying mechanism has been elusive. Here, using single-molecule approaches, we visualize 𝑅𝐵𝐷 opening and closing and probe the 𝑆/𝐴𝐶𝐸2 interaction. Our results show that RBD dynamics affect 𝐴𝐶𝐸2 binding but not unbinding. The resulting modulation is quantitatively predicted by a conformational selection model in which each protomer behaves independently. Our work reveals a general molecular mechanism affecting binding affinity without altering binding strength, helping to understand coronavirus infection and immune evasion.

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Section: Main Textmentioning

confidence: 99%

Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection

Saha,

Fernanadez,

Sumbul

et al. 2024

Preprint

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“…In addition, convalescent plasma contains neutralizing antibodies that bind to different regions on S protein and inhibit viral entry by different mechanisms [64,65]. Moreover, various synthetic molecules bind to S protein and inhibit binding of to ACE2, block SARS-CoV-2 fusion with the cell membrane [66], or inhibit cleavage of polyproteins required for SARS-CoV-2 replication such as viral proteases, 3CLpro and PLpro [67]. Remdesivir and favipiravir are two of the most promising antiviral drugs that have been tested [68,69].…”

Section: Novel Drugsmentioning

confidence: 99%

Intervention Strategies for Seasonal and Emerging Respiratory Viruses with Drugs and Vaccines Targeting Viral Surface Glycoproteins

Tripp

Stambas

2021

Viruses

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Vaccines and therapeutics targeting viral surface glycoproteins are a major component of disease prevention for respiratory viral diseases. Over the years, vaccines have proven to be the most successful intervention for preventing disease. Technological advances in vaccine platforms that focus on viral surface glycoproteins have provided solutions for current and emerging pathogens like SARS-CoV-2, and our understanding of the structural basis for antibody neutralization is guiding the selection of other vaccine targets for respiratory viruses like RSV. This review discusses the role of viral surface glycoproteins in disease intervention approaches.

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A Frame-by-Frame Glance at Membrane Fusion Mechanisms: From Viral Infections to Fertilization

et al. 2023

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Viral entry and fertilization are distinct biological processes that share a common mechanism: membrane fusion. In viral entry, enveloped viruses attach to the host cell membrane, triggering a series of conformational changes in the viral fusion proteins. This results in the exposure of a hydrophobic fusion peptide, which inserts into the host membrane and brings the viral and host membranes into close proximity. Subsequent structural rearrangements in opposing membranes lead to their fusion. Similarly, membrane fusion occurs when gametes merge during the fertilization process, though the exact mechanism remains unclear. Structural biology has played a pivotal role in elucidating the molecular mechanisms underlying membrane fusion. High-resolution structures of the viral and fertilization fusion-related proteins have provided valuable insights into the conformational changes that occur during this process. Understanding these mechanisms at a molecular level is essential for the development of antiviral therapeutics and tools to influence fertility. In this review, we will highlight the biological importance of membrane fusion and how protein structures have helped visualize both common elements and subtle divergences in the mechanisms behind fusion; in addition, we will examine the new tools that recent advances in structural biology provide researchers interested in a frame-by-frame understanding of membrane fusion.

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FRETing over SARS-CoV-2: Conformational Dynamics of the Spike Glycoprotein

Cited by 3 publications

References 11 publications

Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection

Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection

Intervention Strategies for Seasonal and Emerging Respiratory Viruses with Drugs and Vaccines Targeting Viral Surface Glycoproteins

A Frame-by-Frame Glance at Membrane Fusion Mechanisms: From Viral Infections to Fertilization

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