Article
Virology
Laura Albentosa-Gonzalez, Nereida Jimenez de Oya, Armando Arias, Pilar Clemente-Casares, Miguel angel Martin-Acebes, Juan Carlos Saiz, Rosario Sabariegos, Antonio Mas
Summary: This study found that Akt kinase plays an important role in flavivirus replication, with specific differences among different viruses. Treatment with Akt inhibitors reduced titers of USUV and ZIKV in cell culture, but not WNV. Further investigations are needed to explore the PI3K/Akt/mTOR pathway as a potential antiviral target.
Article
Chemistry, Multidisciplinary
Asmat Ullah, Atia-tul-Wahab, Peng Gong, Abdul Mateen Khan, M. Iqbal Choudhary
Summary: The rapid spread of dengue virus is a major health problem worldwide. This study evaluated 75 compounds for their ability to interact with NS5 protein and identified 12 potential antiviral agents against dengue virus.
Article
Pharmacology & Pharmacy
Charlotte Flory, Kitti Wing Ki Chan, Amanda Makha Bifani, Milly Ming Ju Choy, Julien Lescar, Eng Eong Ooi, Norbert Tautz, Subhash G. Vasudevan
Summary: The study investigates the importance of the Val266 residue in the NS5 protein and its impact on Zika virus, with mutational analysis revealing strong positive selection for residue Val266 through serial passaging.
ANTIVIRAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Gopinathan Pillai Sreekanth
Summary: Dengue virus infection is a significant arboviral infection in humans. Non-structural protein 5 (DENV-NS5) of DENV consists of two domains, RdRp and MTase, which play important roles in viral replication. Targeting DENV-NS5 could be a potential therapeutic strategy for dengue virus infection.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
George Minasov, Monica Rosas-Lemus, Ludmilla Shuvalova, Nicole L. Inniss, Joseph S. Brunzelle, Courtney M. Daczkowski, Paul Hoover, Andrew D. Mesecar, Karla J. F. Satchell
Summary: Methylation of viral mRNA caps is essential for translation efficiency, virus replication, and evasion of host cell innate immune responses. The SARS-CoV-2 2'-O-methyltransferase reaction requires divalent cations, preferably Mn2+, and a coronavirus-specific four-residue insert. The unique insert in coronavirus nsp16 alters the capped RNA conformation, making it a potential target for designing selective coronavirus inhibitors.
Review
Biochemistry & Molecular Biology
Sarah E. Strassler, Isobel E. Bowles, Debayan Dey, Jane E. Jackman, Graeme L. Conn
Summary: The SPOUT methyltransferase superfamily is a group of enzymes that modify RNA substrates and play diverse roles in cellular processes. The unique structure and catalytic function of SPOUT enzymes are crucial for substrate recognition and modification.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Ryan L. McCarthy, Kelsey E. Kaeding, Samuel H. Keller, Yu Zhong, Liqin Xu, Antony Hsieh, Yong Hou, Greg Donahue, Justin S. Becker, Oscar Alberto, Bomyi Lim, Kenneth S. Zaret
Summary: McCarthy, Kaeding et al. identified H3K9me3-heterochromatin proteins that repress heterochromatic genes, with ERH playing a key role in global H3K9me3 maintenance in human cells. They also revealed four groups of srHC proteins that repress common genes and repeat elements, expanding our understanding of H3K9me3-based gene repression in vertebrates.
NATURE CELL BIOLOGY
(2021)
Article
Virology
Philipe O. Fernandes, Marcelo A. Chagas, Willian R. Rocha, Adolfo H. Moraes
Summary: NS5 protein plays a crucial role in flavivirus replication and is a promising drug target; most NS5 inhibitor candidates target active sites, but similarity with human enzymes may lead to side effects; identifying new allosteric sites in NS5 could greatly contribute to antiviral development.
CURRENT OPINION IN VIROLOGY
(2021)
Review
Virology
Kyung H. Choi
Summary: During the replication process, flaviviral polymerase NS5 specifically recognizes the SLA promoter to efficiently replicate the viral RNA genome, expanding our understanding of the molecular basis of RNA viruses.
Article
Multidisciplinary Sciences
Laurin Flemmich, Sarah Heel, Sarah Moreno, Kathrin Breuker, Ronald Micura
Summary: Methylation is a common post-transcriptional modification in RNA, where methyltransferases and small organic substances are used as methyl-group donors. A direct link between a riboswitch and site-specific methylation has been uncovered, suggesting that nucleic acid-mediated methylation is an ancient mechanism.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Amit Kumar, Harish Vashisth
Summary: Riboswitches are conserved functional domains in bacteria that specifically bind small molecules to regulate biosynthesis and transport of amino acids and essential metabolites. They have potential as antibacterial drug targets and this study investigated the recognition mechanisms of oxidized metabolites by the NMT1 riboswitch. Electrostatic interactions were found to be central to ligand discrimination and some mutations could strengthen the binding affinities of the ligands. These findings are also relevant for designing novel compounds targeting riboswitches.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Cell Biology
Michaela Dohnalkova, Kyrylo Krasnykov, Mateusz Mendel, Lingyun Li, Olesya Panasenko, Fabienne Fleury-Olela, Cathrine Broberg Vagbo, David Homolka, Ramesh S. Pillai
Summary: Eukaryotic RNA pol II transcripts are capped at the 50 end by the methylated guanosine (m7G) moiety. CMTR1 and CMTR2 catalyze cap-proximal ribose methylations on the first (cap1) and second (cap2) nucleotides, marking RNAs as self to block the innate immune response pathway. Loss of Cmtr1 or Cmtr2 in mice leads to embryonic lethality and misregulation of specific transcripts, while Cmtr1 mutant adult mouse livers exhibit chronic activation of the interferon pathway. Conditional deletion of Cmtr1 in the germline causes infertility, but global translation is unaffected. These findings reveal essential roles of cap1 and cap2 modifications in gene regulation and immune response evasion.
Article
Multidisciplinary Sciences
Diego J. Paez-Moscoso, David Ho, Lili Pan, Katie Hildebrand, Kristi L. Jensen, Michaella J. Levy, Laurence Florens, Peter Baumann
Summary: Most eukaryotes maintain telomeres using a specialized reverse transcriptase. This study found that Thc1, Bmc1, and Pof8 form a complex in fission yeast and are involved in telomerase biogenesis, which is crucial for telomerase activity and telomere length maintenance.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Carolin P. M. Scheitl, Mateusz Mieczkowski, Hermann Schindelin, Claudia Hoebartner
Summary: RNA-catalyzed RNA methylation has been found to be part of the catalytic repertoire of ribozymes. The crystal structure of methyltransferase ribozyme MTR1 has been determined, revealing a guanine-binding site similar to natural guanine riboswitches. The structure also suggests the involvement of a protonated cytidine in the methyl transfer reaction. The synergistic effect of 2'-O-methylated ribose residues in the active site accelerates methyl group transfer. These findings suggest that modified nucleotides may have played a role in early RNA catalysis and that metabolite-binding riboswitches resemble inactivated ribozymes.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Han Liao, Anushri Gaur, Hunter McConie, Amirtha Shekar, Karen Wang, Jeffrey T. Chang, Ghislain Breton, Catherine Denicourt
Summary: NOP2/NSUN1 catalyzes the deposition of m(5)C at position 4447 on the 28S rRNA, and regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs. Additionally, NOP2/NSUN1 facilitates the recruitment and stable assembly of U3 and U8 snoRNAs into snoRNP complexes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Electrochemistry
Tugba Ozer, Cynthia McCord, Brian J. Geiss, David Dandy, Charles S. Henry
Summary: A new amine functionalized electrochemical immunosensor for label-free detection of Escherichia coli using modified thermoplastic electrodes was reported, with successful application in urine samples for selective and sensitive detection of the bacteria. The sensor showed high specificity and sensitivity, making it suitable for accurate detection of different pathogenic bacteria.
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
(2021)
Article
Microbiology
Anna Fagre, Juliette Lewis, Miles Eckley, Shijun Zhan, Savannah M. Rocha, Nicole R. Sexton, Bradly Burke, Brian Geiss, Olve Peersen, Todd Bass, Rebekah Kading, Joel Rovnak, Gregory D. Ebel, Ronald B. Tjalkens, Tawfik Aboellail, Tony Schountz
Summary: The study found that deer mice are susceptible to SARS-CoV-2 and the virus can persist for a long time in their bodies, with efficient transmission to other deer mice. This suggests the potential for sustained transmission in natural populations of deer mice.
Article
Virology
James S. Terry, Loran BR. Anderson, Michael S. Scherman, Carley E. McAlister, Rushika Perera, Tony Schountz, Brian J. Geiss
Summary: New monoclonal antibodies targeting the SARS-CoV-2 nucleocapsid protein, specifically mBG86, have been developed and validated for various analyses. The variable regions of six select clones were sequenced and epitope mapping was performed, showing promising value in the fight against COVID-19.
Review
Cell Biology
Kelly E. Du Pont, Martin McCullagh, Brian J. Geiss
Summary: Flaviviruses are a major health concern due to the high risk of infection for over half of the world's population and the lack of antiviral therapeutics. NS3 helicase is essential for unwinding viral RNA structures during replication, and its function is dependent on ATP. Conserved structural motifs within NS3 play crucial roles in RNA helicase function, with only three motifs well characterized in flaviviruses.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Article
Chemistry, Analytical
Nicholas Grant, Brian Geiss, Stuart Field, August Demann, Thomas W. Chen
Summary: Microfluidics offer advantages to Point of Care devices by reducing reagent use and device size. However, challenges still exist in integrating all supporting hardware and software. This paper demonstrates a self-contained, battery-powered handheld unit capable of operating an EWOD device for DNA extraction and isolation, representing a promising step towards portable microfluidic devices.
Article
Chemistry, Multidisciplinary
Isabelle C. Samper, Ana Sanchez-Cano, Wisarut Khamcharoen, Ilhoon Jang, Weena Siangproh, Eva Baldrich, Brian J. Geiss, David S. Dandy, Charles S. Henry
Summary: A novel low-cost electrochemical capillary-flow device was developed for rapid detection of SARS-CoV-2 antibodies within 20 minutes without the need for sample preparation. The device integrates blood-filtration membrane for plasma extraction and automated steps of an ELISA, providing accurate and reliable results for point-of-care testing. The novelty lies in the integration of sensitive electrochemical detection with capillary-flow immunoassay, showing potential for aiding the diagnosis of infectious diseases at the point of care.
Article
Chemistry, Analytical
Isabelle C. Samper, Catherine J. McMahon, Melissa S. Schenkel, Kaylee M. Clark, Wisarut Khamcharoen, Loran B. R. Anderson, James S. Terry, Emily N. Gallichotte, Gregory D. Ebel, Brian J. Geiss, David S. Dandy, Charles S. Henry
Summary: A highly sensitive electrochemical immunoassay has been developed for quantitatively detecting the presence of SARS-CoV-2 virus in patient nasopharyngeal samples. The assay demonstrates high specificity and sensitivity, meeting the criteria for POC COVID-19 diagnostic tests set by the World Health Organization.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Zachary D. Call, Ilhoon Jang, Brian J. Geiss, David S. Dandy, Charles S. Henry
Summary: Urinary tract infections (UTIs) are a common and potentially serious condition. Current diagnostic methods are expensive and time-consuming. Magnetophoresis, a method for separating and analyzing cells of interest, has been combined with paper-based microfluidic devices to enable low-cost and simple operation. This study successfully detected E. coli using this hybrid method.
ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Aaron A. Thompson, Michael B. Harbut, Pei-Pei Kung, Nathan K. Karpowich, Jeffrey D. Branson, Joanna C. Grant, Deborah Hagan, Heather A. Pascual, Guoyun Bai, Reza Beheshti Zavareh, Heather R. Coate, Bernard C. Collins, Marjorie Cote, Christine F. Gelin, Kelly L. Damm-Ganamet, Hadi Gholami, Adam R. Huff, Luis Limon, Kevin J. Lum, Puiying A. Mak, Kohki M. Nakafuku, Edmund V. Price, Amy Y. Shih, Mandana Tootoonchi, Nadeem A. Vellore, Jocelyn Wang, Na Wei, Jeannie Ziff, Scott B. Berger, James P. Edwards, Agnes Gardet, Siquan Sun, Jennifer E. Towne, Jennifer D. Venable, Zhicai Shi, Hariharan Venkatesan, Marie-Laure Rives, Sujata Sharma, Brock T. Shireman, Samantha J. Allen
Summary: NKG2D is a key receptor involved in immune response to infections and stress, but its abnormal signaling is associated with inflammatory and autoimmune diseases. In this study, we identified two series of protein-protein interaction inhibitors for NKG2D using a comprehensive small-molecule hit identification strategy. These inhibitors disrupt ligand binding through allosteric modulation of the NKG2D receptor dimer, resulting in improved potency and physicochemical properties. Our findings demonstrate the potential of targeting NKG2D for immune intervention through allosteric modulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Medicinal
Jocelyn Wang, Kohki M. Nakafuku, Jeannie Ziff, Christine F. Gelin, Hadi Gholami, Aaron A. Thompson, Nathan K. Karpowich, Luis Limon, Heather R. Coate, Kelly L. Damm-Ganamet, Amy Y. Shih, Joanna C. Grant, Marjorie Cote, Puiying A. Mak, Heather A. Pascual, Marie -Laure Rives, James P. Edwards, Jennifer D. Venable, Hariharan Venkatesan, Zhicai Shi, Samantha J. Allen, Sujata Sharma, Pei-Pei Kung, Brock T. Shireman
Summary: Natural killer group 2D (NKG2D) is an activating immunoreceptor that detects and eliminates compromised cells. The abnormal activity of NKG2D/NKG2DL axis is associated with autoimmune diseases. NKG2D inhibitors are attractive targets for immunomodulation.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biotechnology & Applied Microbiology
Charles P. Neff, Mile Cikara, Brian J. Geiss, G. Thomas Caltagirone, Albert Liao, Shaikh M. Atif, Bradley Macdonald, Richard Schaden
Summary: The study developed aptamers against the SARS-CoV-2 Nucleocapsid protein as alternative detection reagents in antigen assays. The aptamers showed high sensitivity and specificity, detecting low concentrations of the protein and differentiating the Omicron variant. These findings support the use of aptamers in current tests and the reselection method for emerging viral strains.
CURRENT RESEARCH IN BIOTECHNOLOGY
(2023)
Article
Chemistry, Analytical
Cody Carrell, Ilhoon Jang, Jeremy Link, James S. Terry, Zachary Call, Yosita Panraksa, Orawon Chailapakul, David S. Dandy, Brian J. Geiss, Charles S. Henry
Summary: A capillary-driven microfluidic sequential flow device was developed for at-home or doctor's office use, to perform enzyme-linked immunosorbent assay (ELISA) for serology testing. This device provides critical information for managing COVID-19 infections, immunity status, and vaccination status.
ANALYTICAL METHODS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Jacob Deroo, Christopher Snow, Ning Zhao, Tim Stasevich, Brian Geiss, Christopher Snow
Article
Chemistry, Analytical
Sidhartha Jain, David S. Dandy, Brian J. Geiss, Charles S. Henry
Summary: The sensitive nucleic acid detection method based on padlock probe rolling circle amplification, nuclease protection, and lateral flow detection has been developed for use in resource-limited settings. By combining these techniques, the method allows for detection of antimicrobial resistance genes and specific pathogens such as SARS-CoV-2 with high sensitivity.
Article
Chemistry, Analytical
Ilhoon Jang, Hyunwoong Kang, Simon Song, David S. Dandy, Brian J. Geiss, Charles S. Henry
Summary: Capillary-driven microfluidic devices made from paper and polyester film are commonly used due to their low cost and lack of external pumps. However, controlling flow in these devices can be challenging due to the sole reliance on capillary forces. This study introduces new flow control methods, such as push and burst valve systems, for increased functionality in laminate capillary-driven microfluidic devices. These methods enable precise control of flow direction, concentration, and velocity, ultimately offering new design possibilities for on-site analysis in various fields.