Jeremy W. Prokop, Sheryl Alberta, Martin Witteveen-Lane, Samantha Pell, Hosam A. Farag, Disha Bhargava, Robert M. Vaughan, Austin Frisch, Jacob Bauss, Humza Bhatti, Sanjana Arora, Charitha Subrahmanya, David Pearson, Austin Goodyke, Mason Westgate, Taylor W. Cook, Jackson T. Mitchell, Jacob Zieba, Matthew D. Sims, Adam Underwood, Habiba Hassouna, Surender Rajasekaran, Maximiliano A. Tamae Kakazu, Dave Chesla, Rosemary Olivero, Adam J. Caulfield
{"title":"SARS-CoV-2 基因分型凸显了尖峰蛋白漂移与其他重要蛋白无关的难题","authors":"Jeremy W. Prokop, Sheryl Alberta, Martin Witteveen-Lane, Samantha Pell, Hosam A. Farag, Disha Bhargava, Robert M. Vaughan, Austin Frisch, Jacob Bauss, Humza Bhatti, Sanjana Arora, Charitha Subrahmanya, David Pearson, Austin Goodyke, Mason Westgate, Taylor W. Cook, Jackson T. Mitchell, Jacob Zieba, Matthew D. Sims, Adam Underwood, Habiba Hassouna, Surender Rajasekaran, Maximiliano A. Tamae Kakazu, Dave Chesla, Rosemary Olivero, Adam J. Caulfield","doi":"10.3390/microorganisms12091863","DOIUrl":null,"url":null,"abstract":"As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike.","PeriodicalId":18667,"journal":{"name":"Microorganisms","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins\",\"authors\":\"Jeremy W. Prokop, Sheryl Alberta, Martin Witteveen-Lane, Samantha Pell, Hosam A. Farag, Disha Bhargava, Robert M. Vaughan, Austin Frisch, Jacob Bauss, Humza Bhatti, Sanjana Arora, Charitha Subrahmanya, David Pearson, Austin Goodyke, Mason Westgate, Taylor W. Cook, Jackson T. 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Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike.\",\"PeriodicalId\":18667,\"journal\":{\"name\":\"Microorganisms\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microorganisms\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3390/microorganisms12091863\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microorganisms","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/microorganisms12091863","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins
As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike.
期刊介绍:
Microorganisms (ISSN 2076-2607) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to prokaryotic and eukaryotic microorganisms, viruses and prions. It publishes reviews, research papers and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.