Article
Parasitology
Dorien Mabille, Kayhan Ilbeigi, Sarah Hendrickx, Marzuq A. Ungogo, Fabian Hulpia, Cai Lin, Louis Maes, Harry P. de Koning, Serge Van Calenbergh, Guy Caljon
Summary: Animal trypanosomiasis is a parasitic disease with significant socio-economic impact. This study evaluated the potential use of antitrypanosomal nucleosides as a treatment for animal trypanosomiasis and identified promising compounds with excellent in vitro activity. Compound 7 and compound 8 exhibited broad spectrum anti-animal trypanosomiasis activity in mouse models, but with varying efficacy.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2022)
Review
Cell Biology
Xingxing Xu, Zixuan Li, Xueying Yao, Nannan Sun, Junbiao Chang
Summary: Gastrointestinal malignancies are common digestive system tumors worldwide. Nucleoside analogues have been widely used as anticancer drugs for the treatment of gastrointestinal malignancies, but their efficacy is limited due to low permeability, enzymatic deamination, inefficient phosphorylation, chemoresistance, and other issues. Prodrug strategies have been employed to improve pharmacokinetic properties and address safety and drug-resistance issues. This review provides an overview of recent developments in prodrug strategies using nucleoside analogues for the treatment of gastrointestinal malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Manal J. Natto, Fabian Hulpia, Eric R. Kalkman, Susan Baillie, Amani Alhejeli, Yukiko Miyamoto, Lars Eckmann, Serge Van Calenbergh, Harry P. de Koning
Summary: The study introduces a novel drug sensitivity assay and identifies a new class of potent anti-trichomonas agents with promising in vivo activity in a murine trichomoniasis model. These purine nucleoside analogues show excellent inhibitory effects against Trichomonas growth and offer potential as new antitrichomonal agents.
ACS INFECTIOUS DISEASES
(2021)
Article
Virology
Emma Cosaro, Jully Pires, Diego Castillo, Brian G. Murphy, Krystle L. Reagan
Summary: This study compared the efficacy of antiviral medications GS-442514 and remdesivir in treating feline infectious peritonitis (FIP), and found no significant difference in survival rate between the two medications. Both GS-442514 and remdesivir were proven to be safe and effective in treating FIP, but further optimization is needed in the initial 48 hours of treatment.
Review
Chemistry, Multidisciplinary
Ravi Goyal, Rajni Bala, Rakesh K. Sindhu, Mehrukh Zehravi, Reecha Madaan, Sarker Ramproshad, Banani Mondal, Abhijit Dey, Md Habibur Rahman, Simona Cavalu
Summary: Plants have been used for their medicinal properties since ancient times, providing various phytomolecules that synergistically benefit human well-being. The outbreak of SARS-CoV-2 has led scientists to explore less toxic anti-viral phytomolecules and environmentally friendly therapeutic molecules for the development of phytopharmaceuticals. This article summarizes bioactive molecules with anti-viral properties, their mode of action, and their potential application in treating viral diseases, with a particular focus on coronaviruses and nano-formulations for improved bioavailability.
Review
Public, Environmental & Occupational Health
T. C. Nino-Sandoval, N. S. Rocha, F. W. Sarinho, C. F. de M. Vasconcelos, A. F. de M. Vasconcelos, B. C. Vasconcelos
Summary: Autohemotherapy has shown positive effects in treating viral diseases such as hepatitis B, hepatitis C, and Coronavirus according to the analysis of literature. More prospective comparative studies are needed to further validate its efficacy.
Review
Virology
Teresa Ng, Ivan Correia, Jane Seagal, David A. DeGoey, Michael R. Schrimpf, David J. Hardee, Elizabeth L. Noey, Warren M. Kati
Summary: The COVID-19 vaccines have been successful in protecting against infection and reducing disease severity, but they face challenges such as waning immunity and reduced effectiveness against variants. Therefore, the discovery of antiviral drugs is crucial in addressing this pandemic.
Article
Chemistry, Medicinal
Wendy Tran, Ali S. Kusay, Paige M. E. Hawkins, Chen-Yi Cheung, Gayathri Nagalingam, Venugopal Pujari, Daniel J. Ford, Alexander Stoye, Jessica L. Ochoa, Rebecca E. Audette, Elinor Hortle, Stefan H. Oehlers, Susan A. Charman, Roger G. Linington, Eric J. Rubin, Christopher G. Dowson, David Roper, Dean C. Crick, Thomas Balle, Gregory M. Cook, Warwick J. Britton, Richard J. Payne
Summary: The study reports the design and synthesis of inhibitors targeting Mtb MurX enzyme, showing potent antimicrobial activity against Mycobacterium tuberculosis. These inhibitors have the potential to be developed into new drugs for tuberculosis treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
David C. Schultz, Robert M. Johnson, Kasirajan Ayyanathan, Jesse Miller, Kanupriya Whig, Brinda Kamalia, Mark Dittmar, Stuart Weston, Holly L. Hammond, Carly Dillen, Jeremy Ardanuy, Louis Taylor, Jae Seung Lee, Minghua Li, Emily Lee, Clarissa Shoffler, Christopher Petucci, Samuel Constant, Marc Ferrer, Christoph A. Thaiss, Matthew B. Frieman, Sara Cherry
Summary: This study screened and validated 122 drugs with antiviral activity and selectivity against SARS-CoV-2 out of approximately 18,000 drugs. Among them are the approved antivirals remdesivir and molnupiravir. The study also found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogues synergistically inhibits SARS-CoV-2 infection.
Review
Oncology
Fabin Han, Yanming Liu, Mei Mo, Juanli Chen, Cheng Wang, Yong Yang, Jibiao Wu
Summary: The rapid spread of COVID-19 has led to a search for effective treatments, with controversial findings on certain therapies. Research is ongoing to investigate the molecular mechanisms of various therapeutic agents against SARS-CoV2.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Jacob M. Sawyer, Kellan T. Passow, Daniel A. Harki
Summary: Fluorescent nucleosides are important chemical tools in biochemical research and are widely used in nucleic acids for various applications. The commonly used 2-aminopurine-2'-deoxyribonucleoside (2APN) has limitations in terms of Stokes shift, molar extinction coefficient, and quantum yield. In this study, we introduced a new fluorescent nucleoside, 4-cyanoindole-2'-deoxyribonucleoside (4CIN), which showed improved photophysical characteristics compared to 2APN. We further synthesized analogues combining the features of 2APN and 4CIN, and evaluated their photophysical properties. Nucleosides 2-6 demonstrated diverse photophysical properties, with some outperforming 4CIN. The structure-function relationship data obtained from this study can guide the design of next-generation fluorescent indole nucleosides.
Article
Veterinary Sciences
Sally J. Coggins, Jacqui M. Norris, Richard Malik, Merran Govendir, Evelyn J. Hall, Benjamin Kimble, Mary F. Thompson
Summary: This study aimed to evaluate the efficacy and tolerability of the therapeutic drugs GS-441524 and its prodrug remdesivir (GS-5734) for feline infectious peritonitis (FIP). The results showed that intravenous administration of remdesivir and oral administration of GS-441524 were effective and well-tolerated treatments for FIP. When monitoring treatment efficacy, early emphasis on clinical response and later emphasis on clinicopathologic response appear to be prudent.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Vasiliki Daikopoulou, Panagiotis Apostolou, Sofia Mourati, Ioanna Vlachou, Maria Gougousi, Ioannis Papasotiriou
Summary: Researchers synthesized a group of new nucleoside analogues and evaluated their effects on the polymerase of SARS-CoV-2 through in vitro assays, aiming to discover novel drugs for treating COVID-19.
Article
Multidisciplinary Sciences
Debra Van Egeren, Alexander Novokhodko, Madison Stoddard, Uyen Tran, Bruce Zetter, Michael S. Rogers, Diane Joseph-McCarthy, Arijit Chakravarty
Summary: The emergence and spread of novel SARS-CoV-2 variants poses a threat to achieving herd immunity against COVID-19. Research suggests that long-term infections with SARS-CoV-2 increase the likelihood of fitter variants emerging, which may occur frequently at a population level. Targeted interventions towards these low-probability stochastic events could help slow the emergence of advantageous viral variants in the patient population.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Sebastian C. Cosgrove, Gavin J. Miller
Summary: This article discusses the recent advances and challenges in using biocatalytic synthesis to access nucleoside analogues. It focuses on the methodology concepts of using enzymes to access diverse nucleoside analogue space and producing key building blocks, as well as the use of biocatalytic cascades for de novo syntheses of nucleoside analogue drugs. The article also mentions the recent advances in enzymatic nucleoside synthesis technologies, such as immobilization and flow, and highlights the need for tandem approaches across molecular microbiology and chemical synthesis to unlock the potential of next generation nucleoside analogue drug discovery.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
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
Cell Biology
Laura J. Stevens, Andrea J. Pruijssers, Hery W. Lee, Calvin J. Gordon, Egor P. Tchesnokov, Jennifer Gribble, Amelia S. George, Tia M. Hughes, Xiaotao Lu, Jiani Li, Jason K. Perry, Danielle P. Porter, Tomas Cihlar, Timothy P. Sheahan, Ralph S. Baric, Matthias Gotte, Mark R. Denison
Summary: This study identified mutations in the nonstructural protein 12 RNA-dependent RNA polymerase of the SARS-CoV-2 virus that confer resistance to the antiviral drug remdesivir. These mutations result in decreased preference for the drug as a substrate and can be transferred to other betacoronaviruses, causing replication defects and up to 38-fold resistance. The findings highlight the importance of further research to understand and prevent the emergence of remdesivir resistance mutations in clinical settings.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
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)
