Article
Pharmacology & Pharmacy
Mahmoud Kandeel, Mizuki Yamamoto, Byoung Kwon Park, Abdulla Al-Taher, Aya Watanabe, Jin Gohda, Yasushi Kawaguchi, Kentaro Oh-hashi, Hyung-Joo Kwon, Jun-ichiro Inoue
Summary: A highly potent set of peptides was designed to prevent MERS-CoV fusion through competition with HR2 at its HR1 binding site. These peptides demonstrated strong inhibition of MERS-CoV cell-cell fusion and plaque formation, with no cytotoxic effects at high concentrations, suggesting their potential as promising antiviral agents.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Chemistry, Medicinal
Thanigaimalai Pillaiyar, Lukas L. Wendt, Manoj Manickam, Maheswaran Easwaran
Summary: Coronaviruses can infect both humans and animals, causing a range of infections. Three beta-coronaviruses, including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, have crossed the species barrier to infect humans. The urgent need for antiviral therapies against these dangerous viruses remains, as no approved vaccines or drugs are currently available.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Multidisciplinary Sciences
Salmaan Sharif, Aamer Ikram, Adnan Khurshid, Muhammad Salman, Nayab Mehmood, Yasir Arshad, Jamal Ahmed, Rana Muhammad Safdar, Lubna Rehman, Ghulam Mujtaba, Jaffar Hussain, Johar Ali, Mehar Angez, Muhammad Masroor Alam, Ribqa Akthar, Muhammad Wasif Malik, Mirza Zeeshan Iqbal Baig, Muhammad Suleman Rana, Muhammad Usman, Muhammad Qaisar Ali, Abdul Ahad, Nazish Badar, Massab Umair, Sana Tamim, Asiya Ashraf, Faheem Tahir, Nida Ali
Summary: The study found 27% of wastewater samples tested positive for SARs-CoV-2, indicating the potential for monitoring viral spread through wastewater surveillance. Additionally, the detection of virus sequence data in wastewater highlights the importance of surveillance for early warning signs.
Article
Multidisciplinary Sciences
Sebenzile K. Myeni, Peter J. Bredenbeek, Robert C. M. Knaap, Tim J. Dalebout, Shessy Torres Morales, Igor A. Sidorov, Marissa E. Linger, Nadia Oreshkova, Sophie van Zanen-Gerhardt, Serge A. L. Zander, Luis Enjuanes, Isabel Sola, Eric J. Snijder, Marjolein Kikkert
Summary: This study demonstrates that the deubiquitinating enzyme inactivation in Middle East respiratory syndrome coronavirus (MERS-CoV) leads to attenuation in mice and provides protection against a lethal challenge. The DUB-negative rMERS-CoVMA robustly replicates in the lungs but does not cause clinical symptoms. Intranasal vaccination with DUB-negative rMERS-CoVMA induces strong neutralizing antibody responses and sterilizing immunity.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Chamandi S. Dampalla, Matthew J. Miller, Yunjeong Kim, Alexandria Zabiegala, Harry Nhat Nguyen, Trent K. Madden, Hayden A. Thurman, Alexandra J. Machen, Anne Cooper, Lijun Liu, Kevin P. Battaile, Scott Lovell, Kyeong-Ok Chang, William C. Groutas
Summary: The high morbidity and mortality of SARS-CoV-2 infection has greatly impacted global public health. Despite progress in vaccine development, the emergence of variants and breakthrough infections remain a major concern. There is a lack of small-molecule therapeutics and prophylactics to counter the spread of SARS-CoV-2 and other coronaviruses. This study focuses on the structure-guided design of potent inhibitors of SARS-CoV-2 3C-like protease, showing promising results in inhibiting viral replication.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
J. Gutierrez-Alvarez, J. M. Honrubia, A. Sanz-Bravo, E. Gonzalez-Miranda, R. Fernandez-Delgado, M. T. Rejas, S. Zuniga, I Sola, L. Enjuanes
Summary: Deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) generates a replication-competent propagation-defective RNA replicon. Further combination with accessory open reading frames (ORFs) can enhance the attenuation of the replicon, resulting in highly safe and promising vaccine candidates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Hao Wang, Rongjuan Pei, Xin Li, Weilong Deng, Shuai Xing, Yanan Zhang, Chen Zhang, Shuai He, Hao Sun, Shuqi Xiao, Jin Xiong, Yecheng Zhang, Xinwen Chen, Yaxin Wang, Yu Guo, Bo Zhang, Luqing Shang
Summary: COVID-19 caused by SARS-CoV-2 has resulted in millions of infections and deaths worldwide. Researchers have identified the 3CL protease of SARS-CoV-2 as a potential target for developing drugs. They have successfully designed peptidomimetic inhibitors with excellent antiviral activity against SARS-CoV-2, indicating their potential as drug candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Muya Xiong, Haixia Su, Wenfeng Zhao, Hang Xie, Qiang Shao, Yechun Xu
Summary: The emergence of various coronaviruses in recent decades has posed significant threats to global health, with the ongoing COVID-19 pandemic causing millions of infections and deaths worldwide. The 3C-like protease (3CL(pro)) is seen as a promising target for antiviral intervention due to its essential role in viral replication and its conserved structural features among different coronaviruses. Research focusing on the crystal structures of 3CL(pro) and their inhibitors aims to provide insights into inhibition mechanisms and guide future drug discovery efforts.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Ana C. Puhl, Ethan J. Fritch, Thomas R. Lane, Longping Tse, Boyd L. Yount, Carolina Q. Sacramento, Natalia Fintelman-Rodrigues, Tatyana Almeida Tavella, Fabio Trindade Maranhao Costa, Stuart Weston, James Logue, Matthew Frieman, Lakshmanane Premkumar, Kenneth H. Pearce, Brett L. Hurst, Carolina Horta Andrade, James A. Levi, Nicole J. Johnson, Samantha C. Kisthardt, Frank Scholle, Thiago Moreno L. Souza, Nathaniel John Moorman, Ralph S. Baric, Peter B. Madrid, Sean Ekins
Summary: SARS-CoV-2, a newly identified virus causing global impact, poses challenges in discovering small-molecule inhibitors for reversing disease severity. Drug repurposing, especially targeting RNA polymerase like remdesivir, has shown promise in early-stage disease treatment. Previous studies on drugs active against Ebola viruses suggest potential efficacy against SARS-CoV-2.
Article
Microbiology
Javier Gutierrez-Alvarez, Jose M. Honrubia, Raul Fernandez-Delgado, Li Wang, Carlos Castano-Rodriguez, Sonia Zuniga, Isabel Sola, Luis Enjuanes
Summary: There is a potential vaccine candidate for MERS-CoV developed by generating mutants with partial deletions in the E protein, which has been shown to be attenuated and provide complete protection against virulent MERS-CoV. This approach highlights the importance of identifying and targeting virulence factors to design efficient vaccines.
Article
Chemistry, Medicinal
Lucile Brier, Haitham Hassan, Xavier Hanoulle, Valerie Landry, Danai Moschidi, Lowiese Desmarets, Yves Rouille, Julie Dumont, Adrien Herledan, Sandrine Warenghem, Catherine Piveteau, Paul Carr, Sarah Ikherbane, Francois-Xavier Cantrelle, Elian Dupre, Jean Dubuisson, Sandrine Belouzard, Florence Leroux, Benoit Deprez, Julie Charton
Summary: Since the end of 2019, the global outbreak of the coronavirus SARS-CoV-2 has caused a significant increase in infections and deaths worldwide. Researchers have identified two proteases, 3CLpro and papain-like protease, encoded by the virus that play a crucial role in the virus lifecycle. Targeting the 3CLpro, which is highly conserved within this viral family, a screening of over 89,000 small molecules led to the discovery of a potent inhibitor of the SARS-CoV-2 3CLpro. The mechanism of inhibition, interaction with the protease, specificity against host proteases, and promising antiviral properties in cells are reported.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Mujeeb Khan, Syed F. Adil, Hamad Z. Alkhathlan, Muhammad N. Tahir, Sadia Saif, Merajuddin Khan, Shams T. Khan
Summary: The article summarizes the three deadly pandemics associated with novel coronaviruses that humans have witnessed in the twenty-first century: SARS, MERS, and COVID-19. Specifically, it describes the epidemiological characteristics of COVID-19, such as transmission, death rate, and discusses various treatment strategies and different approaches to vaccine development.
Review
Biochemistry & Molecular Biology
Ridhima Kaul, Pradipta Paul, Sanjay Kumar, Dietrich Buesselberg, Vivek Dhar Dwivedi, Ali Chaari
Summary: This review summarizes the activities and structure-activity relationships of flavonoids in combating SARS-CoV-2 from in vitro studies to clinical research. The study found that flavonoids such as quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid show promising activities against SARS-CoV-2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Bo Qin, Gregory B. Craven, Pengjiao Hou, Julian Chesti, Xinran Lu, Emma S. Child, Rhodri M. L. Morgan, Wenchao Niu, Lina Zhao, Alan Armstrong, David J. Mann, Sheng Cui
Summary: This study successfully applied quantitative irreversible tethering (qIT) to identify fragments that can inhibit the proteases of Enterovirus 71 and SARS-CoV-2, and found that the inhibition could disrupt the active dimeric unit.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Microbiology
Hanan Al-Khalaifah, Mohammad Alotaibi, Afaf Al-Nasser
Summary: This article examines the origin of coronaviruses and the risk of transmission between humans and animals, with a focus on avian coronaviruses and their possible relation to SARS-CoV-2.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Lalita Mazgaeen, Matthew Yorek, Saurabh Saini, Peter Vogel, David K. Meyerholz, Thirumala-Devi Kanneganti, Prajwal Gurung
Summary: Mice with a specific amino acid substitution in SHP1 protein (Ptpn6(spin) mice) develop an autoinflammatory disease. When Ptpn6(spin) bone marrow cells are transferred into Cd47-deficient mice, marked weight loss and death occur. The study suggests that gut leakage caused by pathogenic neutrophils may contribute to the morbidity and mortality in Cd47(-/-) mice receiving Ptpn6(spin) cells. IL-1 blockade with anakinra can rescue the disease phenotype.
Editorial Material
Medicine, General & Internal
David K. Meyerholz
Article
Chemistry, Medicinal
Chamandi S. Dampalla, Harry Nhat Nguyen, Athri D. Rathnayake, Yunjeong Kim, Krishani Dinali Perera, Trent K. Madden, Hayden A. Thurman, Alexandra J. Machen, Maithri M. Kashipathy, Lijun Liu, Kevin P. Battaile, Scott Lovell, Kyeong-Ok Chang, William C. Groutas
Summary: The emergence of SARS-CoV-2 has led to the urgent need for effective countermeasures, such as vaccines and direct-acting antivirals. This study focuses on the design of highly potent inhibitors for SARS-CoV-2 and other related coronaviruses. The results show promising candidates with low cytotoxicity and high potency for further development as broad-spectrum antivirals.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Athmane Teghanemt, Kara Misel-Wuchter, Jace Heath, Andrew Thurman, Priyanjali Pulipati, Garima Dixit, Ramasatya Geesala, David K. Meyerholz, Thorsten Maretzky, Alejandro Pezzulo, Priya D. Issuree
Summary: Regulatory T (T reg) cells are vital in maintaining tolerance and preventing fatal autoimmunity. This study reveals the importance of Tet enzymes and DNA demethylation in promoting Treg cell differentiation in the thymus. Tet3 is specifically involved in the development of CD4 single-positive thymocytes and plays a critical role in TCR-dependent IL-2 production, which is essential for chromatin remodeling and the upregulation of FoxP3.
Editorial Material
Pathology
David K. Meyerholz
VETERINARY PATHOLOGY
(2023)
Article
Biology
David K. Meyerholz, Mariah R. Leidinger, J. Adam Goeken, Thomas R. Businga, Sebastian Vizuett, Allison Akers, Idil Evans, Yan Zhang, John F. Engelhardt
Summary: Our objective was to qualify MUC5AC and MUC5B immunohistochemical techniques to provide a useful tool for studying mucin tissue in CF and other ferret models. Results showed that MUC5AC and MUC5B mucins were most commonly detected in large airways and least in small airways, consistent with goblet cell density in airway surface epithelia. We also found that stomach tissues were enriched in MUC5AC and gallbladder tissues were enriched in MUC5B, similar to human tissues. Qualified techniques for MUC5AC and MUC5B immunohistochemistry will be valuable for mucin tissue studies.
BMC RESEARCH NOTES
(2023)
Article
Chemistry, Multidisciplinary
Sudartip Areecheewakul, Andrea Adamcakova-Dodd, Zeb R. Zacharias, Xuefang Jing, David K. Meyerholz, Kevin L. Legge, Jon C. D. Houtman, Patrick T. O'Shaughnessy, Peter S. Thorne, Aliasger K. Salem
Summary: This study investigated the immunomodulatory effects of inhalation exposure to copper oxide nanoparticles (CuO NPs) in different immune conditions. The results showed that CuO NP exposure decreased T(H)1 and T(H)2 cells and increased T-bet(+) Treg cells in healthy mice. However, CuO NP inhalation exposure resulted in decreased T(H)2 responses and increased T-bet(+) Treg cells in mice with house dust mite (HDM) asthma, and increased T(H)2 cells in AIT-treated asthmatic mice.
Article
Oncology
Jordan L. Kohlmeyer, Joshua J. Lingo, Courtney A. Kaemmer, Amanda Scherer, Akshaya Warrier, Ellen Voigt, Juan A. Raygoza Garay, Gavin R. Mcgivney, Qierra R. Brockman, Amy Tang, Ana Calizo, Kai Pollard, Xiaochun Zhang, Angela C. Hirbe, Christine A. Pratilas, Mariah Leidinger, Patrick Breheny, Michael S. Chimenti, Jessica C. Sieren, Varun Monga, Munir R. Tanas, David K. Meyerholz, Benjamin W. Darbro, Rebecca D. Dodd, Dawn E. Quelle
Summary: Targeting CDK4/6 and MEK inhibitors in MPNSTs can synergistically activate tumor suppressor genes, induce cell death, and reduce tumor survival, while CDK4/6-MEK inhibition can enhance the efficacy of anti-PD-L1 therapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Feng Yuan, Grace N. Gasser, Evan Lemire, Daniel T. Montoro, Karthik Jagadeesh, Yan Zhang, Yifan Duan, Vitaly Ievlev, Kristen L. Wells, Pavana G. Rotti, Weam Shahin, Michael Winter, Bradley H. Rosen, Idil Evans, Qian Cai, Miao Yu, Susan A. Walsh, Michael R. Acevedo, Darpan N. Pandya, Vamsidhar Akurathi, David W. Dick, Thaddeus J. Wadas, Nam Soo Joo, Jeffrey J. Wine, Susan Birket, Courtney M. Fernandez, Hui Min Leung, Guillermo J. Tearney, Alan S. Verkman, Peter M. Haggie, Kathleen Scott, Douglas Bartels, David K. Meyerholz, Steven M. Rowe, Xiaoming Liu, Ziying Yan, Adam L. Haber, Xingshen Sun, John F. Engelhardt
Summary: This study demonstrates the crucial role of ionocytes in controlling airway surface liquid volume and mucociliary clearance through CFTR-dependent ion transport. The creation of conditional genetic ferret models enables the study of ionocyte biology and function, providing insights into human health and disease that have greater evolutionary conservation compared to traditional rodent models.
Article
Multidisciplinary Sciences
Pengfei Li, Biyun Xue, Nicholas J. Schnicker, Lok- Yin Roy Wong, David K. Meyerholz, Stanley Perlman
Summary: The unique region (SUD) in the nonstructural protein Nsp3 of SARS-CoV-2 plays an important role in enhancing viral translation. The study identified a attenuated virus with a mutation in the linker region of Nsp3 and a compensatory mutation in the nucleocapsid protein (N) that restored virulence, revealing the impact of Nsp3-N interactions on virus replication and pathogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Ruiqi Huang, Gabrielle Warner Jenkins, Yunjeong Kim, Robyn L. Stanfield, Amrinder Singh, Maria Martinez-Yamout, Gerard J. Kroon, Jonathan L. Torres, Abigail M. Jackson, Abigail Kelley, Namir Shaabani, Baisen Zeng, Michael Bacica, Wen Chen, Christopher Warner, Jasmina Radoicic, Joongho Joh, Krishani Dinali Perera, Huldah Sang, Tae Kim, Jianxiu Yao, Fangzhu Zhao, Devin Sokd, Dennis R. Burton, Jeff Allen, William Harriman, Waithaka Mwangi, Donghoon Chung, John R. Teijaro, Andrew B. Ward, H. Jane Dyson, Peter E. Wright, Ian A. Wilson, Kyeong-Ok Chang, Duncan Mcgregor, Vaughn V. Smider
Summary: Antibodies derived from cows have the potential to be a new class of therapeutics, capable of neutralizing various SARS-CoV-2 variants and providing protection against disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Lok-Yin Roy Wong, Abby Odle, Emma Luhmann, Douglas C. Wu, Yiquan Wang, Qi Wen Teo, Celeste Ptak, Alan Sariol, Shea Lowery, Matthias Mack, David K. Meyerholz, Nicholas C. Wu, Lilliana Radoshevich, Stanley Perlman
Summary: The internal proteins 8b and 9b of MERS-CoV and SARS-CoV-2 have different roles in mediating pathogenesis in infected animals. MERS-CoV lacking protein 8b expression is more virulent, while SARS-CoV-2 lacking protein 9b expression is attenuated. Additionally, mice infected with MERS-CoV lacking protein 8b expression showed increased levels of interferon and immune cell infiltration.
Article
Veterinary Sciences
David Diaz-Reganon, Vojtech Gabriel, Vanessa Livania, Dongjie Liu, Basant H. Ahmed, Addison Lincoln, Hannah Wickham, Abigail Ralston, Maria M. Merodio, Dipak K. Sahoo, Christopher Zdyrski, David K. Meyerholz, Jonathan P. Mochel, Karin Allenspach
Summary: Recent studies have highlighted the importance of intestinal mucosal changes in chronic enteropathies. This study examined the morphological changes in enterocytes and the ratio of goblet cells to enterocytes in dogs with chronic enteropathies. The results showed significant alterations in enterocyte size and a decreased goblet cell-to-enterocyte ratio in the colon, similar to celiac disease in humans.
VETERINARY SCIENCES
(2023)
Article
Multidisciplinary Sciences
Abigail R. Gress, Christine E. Ronayne, Joshua M. Thiede, David K. Meyerholz, Samuel Okurut, Julia Stumpf, Tailor V. Mathes, Kenneth Ssebambulidde, David B. Meya, Fiona V. Cresswell, David R. Boulware, Tyler D. Bold
Summary: The OX40 protein is proposed as a marker for recently activated CD4 T cells at the infection site in tuberculosis, indicating its potential as a target for immunotherapy.
NATURE COMMUNICATIONS
(2023)