Cryo-EM Study of SARS-CoV-2 Polyprotein in Complex with Main Protease

The polyprotein cleavage by the main protease (Mpro) plays an essential role in the SARS-CoV-2 replication by producing multiple functional nonstructural proteins (nsps) to form the replication transcription complex (RTC) for replicating and transcribing virus RNA genomes. Thus, determining the structure of the polyprotein in complex with Mpro could lead to a deeper understanding of the Mpro cleavage mechanism. The goal of this project is to obtain a high-resolution three-dimensional structure of SARS-CoV-2 polyprotein containing the nsp14-16 region in complex with Mpro by using cryo-electron microscopy (cryo-EM) single-particle reconstruction. For future directions, structural analysis of the SARS-CoV-2 polyprotein with Mpro complex will enhance our understanding of the replication mechanism of SARS-CoV-2 to develop more effective targeted drugs against SARS-CoV-2.

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Work Title Cryo-EM Study of SARS-CoV-2 Polyprotein in Complex with Main Protease
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Open Access
Creators
  1. Kaitlin Lin
License In Copyright (Rights Reserved)
Work Type Research Paper
Acknowledgments
  1. Professor Katsuhiko Murakami
  2. Dr. Manju Narwal
Publication Date April 26, 2024
Deposited April 26, 2024

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Version 1
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    Acknowledgments
    • Professor Katsuhiko Murakami, Dr. Manju Narwal
  • Added Creator Kaitlin Lin
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    License
    • https://rightsstatements.org/page/InC/1.0/
    Description
    • The polyprotein cleavage by the main protease (Mpro) plays an essential role in the SARS-CoV-2 replication by producing multiple functional nonstructural proteins (nsps) to form the replication transcription complex (RTC) for replicating and transcribing virus RNA genomes. Thus, determining the structure of the polyprotein in complex with Mpro could lead to a deeper understanding of the Mpro cleavage mechanism. The goal of this project is to obtain a high-resolution three-dimensional structure of SARS-CoV-2 polyprotein containing the nsp14-16 region in complex with Mpro by using cryo-electron microscopy (cryo-EM) single-particle reconstruction. For future directions, structural analysis of the SARS-CoV-2 polyprotein with Mpro complex will enhance our understanding of the replication mechanism of SARS-CoV-2 to develop more effective targeted drugs against SARS-CoV-2.
    Publication Date
    • 2024-04-26
  • Added Lin_Kaitlin_Thesis_Final.pdf
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