Article
Multidisciplinary Sciences
Chang Liu, Wei Shi, Scott T. Becker, David G. Schatz, Bin Liu, Yang Yang
Summary: This study highlights the crucial role of ExoN in the coronavirus life cycle, its recognition and excision of nucleotide analog inhibitors, and provides insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. The cryo-electron microscopy structures reveal the molecular determinants of ExoN substrate specificity, offering guidance for the rational design of improved anticoronavirus therapies.
Article
Biochemistry & Molecular Biology
Andrew H. Mack, Georgina Menzies, Alex Southgate, D. Dafydd Jones, Thomas R. Connor
Summary: The RNA-dependent RNA polymerase of SARS-CoV-2 is prone to errors, but these errors can be corrected by the exonuclease proofreading mechanism. The interplay between replicase fidelity and environmental pressures affects virus mutagenesis and evolutionary trajectory. A single distal mutation in NSP14 has been shown to significantly impact proofreading, leading to increased mutation accumulation and elevated evolutionary rate. Understanding these changes is crucial for understanding the population-wide evolution of the virus.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Fatemeh Arabi-Jeshvaghani, Fatemeh Javadi-Zarnaghi, Mohamad Reza Ganjalikhany
Summary: The emergence of SARS-CoV-2 and its variants has emphasized the need for novel therapeutics to combat coronaviruses. By analyzing the protein-protein interactions of nsp10 with nsp16 and nsp14, important information for designing antiviral drugs against SARS-CoV-2 was obtained.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Nicholas H. Moeller, Ke Shi, Ozlem Demir, Christopher Belica, Surajit Banerjee, Lulu Yin, Cameron Durfee, Rommie E. Amaro, Hideki Aihara
Summary: This study reveals the structure of the ExoN protein in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which plays a crucial role in the accurate replication of the virus's RNA genome. The structure demonstrates how ExoN binds to its cofactor nsp10 and interacts with RNA substrates. The findings have implications for the development of antiviral drugs and strategies to mitigate the virulence of coronaviruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Marius Walter, Irene P. Chen, Albert Vallejo-Gracia, Ik-Jung Kim, Olga Bielska, Victor L. Lam, Jennifer M. Hayashi, Andrew Cruz, Samah Shah, Frank W. Soveg, John D. Gross, Nevan J. Krogan, Keith R. Jerome, Birgit Schilling, Melanie Ott, Eric Verdin
Summary: This study reveals the interaction between SARS-CoV-2 Nsp14 and human SIRT5 proteins. SIRT5 plays a critical role in viral replication, and its knockout or inhibition reduces viral levels while enhancing the cellular antiviral response.
Article
Biochemistry & Molecular Biology
Quentin Vicens, Jeffrey S. Kieft
Summary: Viral RNA genomes may be small, but they make up for it in complexity with elements like xrRNAs, which resist degradation and play diverse roles during infection. Studies suggest that xrRNAs, found in a variety of RNA viruses, could be a crucial strategy for virus evolution and pathogenicity regulation.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Xiaoyu Niu, Fanzhi Kong, Yixuan J. Hou, Qiuhong Wang
Summary: This study investigated the nsp14-ExoN deficiency in the alphacoronavirus PEDV using reverse genetics. Results showed that variants carrying mutations at the essential functional sites within nsp14-ExoN were either lethal or genetically unstable, highlighting the critical role of nsp14-ExoN in CoV life cycle and its potential as a target for universal anti-CoV drug design.
CELL AND BIOSCIENCE
(2021)
Article
Immunology
Alvaro Lopez-Valinas, Marta Valle, Marta Perez, Ayub Darji, Chiara Chiapponi, Llilianne Ganges, Joaquim Segales, Jose I. Nunez
Summary: Influenza A viruses (IAVs) are constantly evolving, posing a threat to animal and human health. Vaccines can help reduce the spread of swine influenza viruses (SIAV) in farms, but they do not provide complete protection and may potentially favor viral evolution. A study on vaccinated and nonvaccinated pigs challenged with H1N2 SIAV showed that vaccinated animals had a higher proportion of virus mutations, indicating the potential for vaccine-driven evolution.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xia Tang, Wenxun Huang, Juan Kang, Keyue Ding
Summary: Telbivudine treatment in chronic HBV patients led to significant differences in viral quasispecies, with a reduced dN/dS ratio indicating selective constraints from antiviral therapy. Evolution patterns and resistant mutations in the quasispecies varied over a short-term treatment course.
ANTIVIRAL RESEARCH
(2021)
Article
Plant Sciences
Katalin Nemes, Jose F. Gil, Sebastian Liebe, Mansi Mansi, Efstratia Poimenopoulou, Britt-Louise Lennefors, Mark Varrelmann, Eugene I. Savenkov
Summary: This study elucidates the role of exoribonuclease-resistant RNAs (xrRNAs) in the formation of chimeric RNAs in plants. The intermolecular base-pairing interaction between xrRNAs and RNA 2 is crucial for the de novo formation of chimeric RNAs. Knockdown of the XRN4 gene inhibits the biogenesis of xrRNAs and chimeric RNAs.
Article
Biochemistry & Molecular Biology
Josep Gregori, Marta Ibanez-Lligona, Josep Quer
Summary: The rapid evolution of a viral quasispecies in a host, especially during treatment, is compared to the slow evolution of a natural ecosystem. Methods to quantify the evolution of a quasispecies are introduced and simulated examples are given. The correlation between the proposed indices is also discussed and a clinical case is used to demonstrate the efficacy of the proposed methods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Enya Qing, Tom Gallagher
Summary: This study compares the functional differences between the D614G and Omicron BA.1 variants of the SARS-CoV-2 virus and finds that the Omicron variant exhibits higher sensitivity to receptor activation, intermediate conformational states, and membrane fusion-activating proteases. Through domain-exchanged recombinant proteins, specific mutations in the S protein that contribute to these changes are identified. The results provide a structure-function atlas of S protein variations that enhance the transmissibility and infectivity of current and future SARS-CoV-2 variants.
Article
Multidisciplinary Sciences
Adrian Cruz-Gonzalez, Israel Munoz-Velasco, Wolfgang Cottom-Salas, Arturo Becerra, Jose A. Campillo-Balderas, Ricardo Hernandez-Morales, Alberto Vazquez-Salazar, Rodrigo Jacome, Antonio Lazcano
Summary: Nidoviruses and arenaviruses are the only RNA viruses known to encode a 3'-5' exonuclease domain (ExoN). While the ExoN domain plays a key role in the growth of nidoviral genomes, in arenaviruses it functions in suppressing host innate immune signaling. Analysis suggests that these proteins have been acquired multiple times from cellular hosts.
Article
Multidisciplinary Sciences
M. Smerlak
Summary: This paper explores the link between selection for mutational robustness and the navigability of neutral networks, showing that sequences of neutral mutations follow a maximal entropy random walk. The study also revisits a word-game model of evolution, finding that the likelihood of certain substitution sequences can decrease with population size. These counterintuitive results highlight the intersection of evolutionary dynamics, information theory, and physics.
Review
Virology
Mohammed Tahir
Summary: The ongoing pandemic of COVID-19 caused by the novel coronavirus has highlighted the urgent need for effective antiviral therapies. The resistance of SARS-CoV-2 to existing antivirals underscores the importance of identifying new targets for inhibition, such as nsp14-ExoN.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Virology
James Brett Case, Yize Li, Ruth Elliott, Xiaotao Lu, Kevin W. Graepel, Nicole R. Sexton, Everett Clinton Smith, Susan R. Weiss, Mark R. Denison
JOURNAL OF VIROLOGY
(2018)
Article
Virology
Lingshu Wang, Wei Shi, James D. Chappell, M. Gordon Joyce, Yi Zhang, Masaru Kanekiyo, Michelle M. Becker, Neeltje van Doremalen, Robert Fischer, Nianshuang Wang, Kizzmekia S. Corbett, Misook Choe, Rosemarie D. Mason, Joseph G. Van Galen, Tongqing Zhou, Kevin O. Saunders, Kathleen M. Tatti, Lia M. Haynes, Peter D. Kwong, Kayvon Modjarrad, Wing-Pui Kong, Jason S. McLellan, Mark R. Denison, Vincent J. Munster, John R. Mascola, Barney S. Graham
JOURNAL OF VIROLOGY
(2018)
Article
Virology
Andrea J. Pruijssers, Mark R. Denison
CURRENT OPINION IN VIROLOGY
(2019)
Article
Virology
Kevin W. Graepel, Maria L. Agostini, Xiaotao Lu, Nicole R. Sexton, Mark R. Denison
JOURNAL OF VIROLOGY
(2019)
Article
Pharmacology & Pharmacy
Ariane J. Brown, John J. Won, Rachel L. Graham, Kenneth H. Dinnon, Amy C. Sims, Joy Y. Feng, Tomas Cihlar, Mark R. Denison, Ralph S. Baric, Timothy P. Sheahan
ANTIVIRAL RESEARCH
(2019)
Article
Cell Biology
Nianshuang Wang, Osnat Rosen, Lingshu Wang, Hannah L. Turner, Laura J. Stevens, Kizzmekia S. Corbett, Charles A. Bowman, Jesper Pallesen, Wei Shi, Yi Zhang, Kwanyee Leung, Robert N. Kirchdoerfer, Michelle M. Becker, Mark R. Denison, James D. Chappell, Andrew B. Ward, Barney S. Graham, Jason S. McLellan
Article
Virology
Maria L. Agostini, Andrea J. Pruijssers, James D. Chappell, Jennifer Gribble, Xiaotao Lu, Erica L. Andres, Gregory R. Bluemling, Mark A. Lockwood, Timothy P. Sheahan, Amy C. Sims, Michael G. Natchus, Manohar Saindane, Alexander A. Kolykhalov, George R. Painter, Ralph S. Baric, Mark R. Denison
JOURNAL OF VIROLOGY
(2019)
Article
Multidisciplinary Sciences
Timothy P. Sheahan, Amy C. Sims, Sarah R. Leist, Alexandra Schafer, John Won, Ariane J. Brown, Stephanie A. Montgomery, Alison Hogg, Darius Babusis, Michael O. Clarke, Jamie E. Spahn, Laura Bauer, Scott Sellers, Danielle Porter, Joy Y. Feng, Tomas Cihlar, Robert Jordan, Mark R. Denison, Ralph S. Baric
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Timothy P. Sheahan, Amy C. Sims, Shuntai Zhou, Rachel L. Graham, Andrea J. Pruijssers, Maria L. Agostini, Sarah R. Leist, Alexandra Schafer, Kenneth H. Dinnon, Laura J. Stevens, James D. Chappell, Xiaotao Lu, Tia M. Hughes, Amelia S. George, Collin S. Hill, Stephanie A. Montgomery, Ariane J. Brown, Gregory R. Bluemling, Michael G. Natchus, Manohar Saindane, Alexander A. Kolykhalov, George Painter, Jennifer Harcourt, Azaibi Tamin, Natalie J. Thornburg, Ronald Swanstrom, Mark R. Denison, Ralph S. Baric
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Medicine, General & Internal
L. A. Jackson, E. J. Anderson, N. G. Rouphael, P. C. Roberts, M. Makhene, R. N. Coler, M. P. McCullough, J. D. Chappell, M. R. Denison, L. J. Stevens, A. J. Pruijssers, A. McDermott, B. Flach, N. A. Doria-Rose, K. S. Corbett, K. M. Morabito, S. O'Dell, S. D. Schmidt, P. A. Swanson, M. Padilla, J. R. Mascola, K. M. Neuzil, H. Bennett, W. Sun, E. Peters, M. Makowski, J. Albert, K. Cross, W. Buchanan, R. Pikaart-Tautges, J. E. Ledgerwood, B. S. Graham, J. H. Beigel
NEW ENGLAND JOURNAL OF MEDICINE
(2020)
Article
Cell Biology
Andrea J. Pruijssers, Amelia S. George, Alexandra Schafer, Sarah R. Leist, Lisa E. Gralinksi, Kenneth H. Dinnon, Boyd L. Yount, Maria L. Agostini, Laura J. Stevens, James D. Chappell, Xiaotao Lu, Tia M. Hughes, Kendra Gully, David R. Martinez, Ariane J. Brown, Rachel L. Graham, Jason K. Perry, Venice Du Pont, Jared Pitts, Bin Ma, Darius Babusis, Eisuke Murakami, Joy Y. Feng, John P. Bilello, Danielle P. Porter, Tomas Cihlar, Ralph S. Baric, Mark R. Denison, Timothy P. Sheahan
Article
Medicine, General & Internal
E. J. Anderson, N. G. Rouphael, A. T. Widge, L. A. Jackson, P. C. Roberts, M. Makhene, J. D. Chappell, M. R. Denison, L. J. Stevens, A. J. Pruijssers, A. B. McDermott, B. Flach, B. C. Lin, N. A. Doria-Rose, S. O'Dell, S. D. Schmidt, K. S. Corbett, P. A. Swanson, M. Padilla, K. M. Neuzil, H. Bennett, B. Leav, M. Makowski, J. Albert, K. Cross, V. V. Edara, K. Floyd, M. S. Suthar, D. R. Martinez, R. Baric, W. Buchanan, C. J. Luke, V. K. Phadke, C. A. Rostad, J. E. Ledgerwood, B. S. Graham, J. H. Beigel
NEW ENGLAND JOURNAL OF MEDICINE
(2020)
Letter
Medicine, General & Internal
Alicia T. Widge, Nadine G. Rouphael, Lisa A. Jackson, Evan J. Anderson, Paul C. Roberts, Mamodikoe Makhene, James D. Chappell, Mark R. Denison, Laura J. Stevens, Andrea J. Pruijssers, Adrian B. McDermott, Britta Flach, Bob C. Lin, Nicole A. Doria-Rose, Sijy O'Dell, Stephen D. Schmidt, Kathleen M. Neuzil, Hamilton Bennett, Brett Leav, Mat Makowski, Jim Albert, Kaitlyn Cross, Venkata-Viswanadh Edara, Katharine Floyd, Mehul S. Suthar, Wendy Buchanan, Catherine J. Luke, Julie E. Ledgerwood, John R. Mascola, Barney S. Graham, John H. Beigel
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Microbiology
Jennifer Gribble, Laura J. Stevens, Maria L. Agostini, Jordan Anderson-Daniels, James D. Chappell, Xiaotao Lu, Andrea J. Pruijssers, Andrew L. Routh, Mark R. Denison
Summary: Recombination is essential for coronavirus diversity and the emergence of new strains. The mechanisms of CoV recombination are not well understood, but studies have shown extensive and diverse recombination products in CoVs during replication. The nsp14-ExoN protein is crucial for native recombination in CoVs, highlighting its potential as a target for inhibitors to control SARS-CoV-2 and future emerging zoonotic CoVs.
Article
Infectious Diseases
Kathleen Chiotos, Molly Hayes, David W. Kimberlin, Sarah B. Jones, Scott H. James, Swetha G. Pinninti, April Yarbrough, Mark J. Abzug, Christine E. MacBrayne, Vijaya L. Soma, Daniel E. Dulek, Surabhi B. Vora, Alpana Waghmare, Joshua Wolf, Rosemary Olivero, Steven Grapentine, Rachel L. Wattier, Laura Bio, Shane J. Cross, Nicholas O. Dillman, Kevin J. Downes, Kathryn Timberlake, Jennifer Young, Rachel C. Orscheln, Pranita D. Tamma, Hayden T. Schwenk, Philip Zachariah, Margaret Aldrich, David L. Goldman, Helen E. Groves, Gabriella S. Lamb, Alison C. Tribble, Adam L. Hersh, Emily A. Thorell, Mark R. Denison, Adam J. Ratner, Jason G. Newland, Mari M. Nakamura
JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY
(2020)