Real-time observation of native conformations and molecular behaviors of viral fusion proteins using high-speed atomic force microscopy (HS-AFM)

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The objectives of this project are: 1) to record the native conformation viral fusion proteins under physiological conditions using HS-AFM; 2) to visualize the rapid and transient intermediates during conformational changes triggered by acidic conditions using HS-AFM; 3) to elucidate the conformational dynamic of viral fusion proteins when interacting with exosomes or antibodies using HS-AFM. The PI has implemented HS-AFM to perform nanoscopic elucidation of SARS-CoV-2 spike (S) protein structural dynamics during its interaction with neutralizing antibodies (Objective 3). Certain neutralizing antibodies promote the transition of RBD from its close conformation to open confirmation to enhance RBD-ACE2 interaction. This effect is known as antibody-dependent enhancement effect (ADE). This study reveals that HS-AFM could be worked as an efficient nanoscopic assessment platform for S NAb testing. This study has been published in a well-reputed journal, Nano Letters. Furthermore, this study has also been presented in several domestic conferences. Envelope protein (E protein) of Dengue virus will be investigated in the near future.