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

• DOI: 10.1002/prot.26250
• Publication Date: 2021-09-28T06:11:53Z
• Authors: 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 Venkatac...; Steven Arnold; Luz Helena Alfaro...; Kevin Catalfano; Aaliyah Khan; Erika McCarthy; Sophia Staggers; Brea 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‐...; Stephanie Laporte; Evan Lenkeit; Kailey Martin; Marilyn Orellana; Melanie Ortiz‐Alv...; 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
• Keywords: Pandemic; 2019-20 coronavirus outbreak; Proteome; Betacoronavirus; Coronavirus Infections; Coronavirus; Sars virus

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