Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first 6 months of the COVID-19 pandemic

Joseph H. Lubin, Christine Zardecki, Elliott M. Dolan, Changpeng Lu, Zhuofan Shen, Shuchismita Dutta, John D. Westbrook, Brian P. Hudson, David S. Goodsell, Jonathan K. Williams, Maria Voigt, Vidur Sarma, Lingjun Xie, Thejasvi Venkatachalam, Steven Arnold, Luz Helena Alfaro Alvarado, Kevin Catalfano, Aaliyah Khan, Erika McCarthy, Sophia StaggersBrea Tinsley, Alan Trudeau, Jitendra Singh, Lindsey Whitmore, Helen Zheng, Matthew Benedek, Jenna Currier, Mark Dresel, Ashish Duvvuru, Britney Dyszel, Emily Fingar, Elizabeth M. Hennen, Michael Kirsch, Ali A. Khan, Charlotte Labrie-Cleary, Stephanie Laporte, Evan Lenkeit, Kailey Martin, Marilyn Orellana, Melanie Ortiz-Alvarez de la Campa, Isaac Paredes, Baleigh Wheeler, Allison Rupert, Andrew Sam, Katherine See, Santiago Soto Zapata, Paul A. Craig, Bonnie L. Hall, Jennifer Jiang, Julia R. Koeppe, Stephen A. Mills, Michael J. Pikaart, Rebecca Roberts, Yana Bromberg, J. Steen Hoyer, Siobain Duffy, Jay Tischfield, Francesc X. Ruiz, Eddy Arnold, Jean Baum, Jesse Sandberg, Grace Brannigan, Sagar D. Khare, Stephen K. Burley

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding the molecular evolution of the SARS-CoV-2 virus as it continues to spread in communities around the globe is important for mitigation and future pandemic preparedness. Three-dimensional structures of SARS-CoV-2 proteins and those of other coronavirusess archived in the Protein Data Bank were used to analyze viral proteome evolution during the first 6 months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48 000 viral isolates revealed how each one of 29 viral proteins have undergone amino acid changes. Catalytic residues in active sites and binding residues in protein–protein interfaces showed modest, but significant, numbers of substitutions, highlighting the mutational robustness of the viral proteome. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for potential drug discovery targets and the four structural proteins that comprise the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and protein–protein and protein–nucleic acid interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

Original languageEnglish (US)
JournalProteins: Structure, Function and Bioinformatics
DOIs
StateAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Keywords

  • COVID-19
  • SARS-CoV-2
  • coronavirus
  • databases
  • evolution
  • molecular
  • pandemics
  • protein
  • viral proteins

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