Article
Biochemistry & Molecular Biology
Yun-Sang Tang, Wai-Kin So, Ka-Leung Andy Ng, Ka-Pun Chris Mok, Pang-Chui Shaw
Summary: This study identified host heterogeneous nuclear ribonucleoprotein C as an interacting partner of influenza A virus nucleoprotein and confirmed its negative regulatory role in viral growth. The findings not only enhance our understanding of the influenza virus transmission mechanism but also provide a new research direction for the development of anti-influenza drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Fakhar E. Waqas, Mahmoud Shehata, Walid A. M. Elgaher, Antoine Lacour, Naziia B. Kurmasheva, Fabio Begnini, Anders Kiib, Julia Dahlmann, Chutao Chen, Andreas Pavlou, Thomas Poulsen, Sylvia Merkert, Ulrich S. Martin, Ruth Olmer, David S. Olagnier, Anna K. H. Hirsch, Stephan S. Pleschka, Frank Pessler
Summary: Virus infections can cause organ damage through inflammation and oxidative stress. This study evaluated NRF2 activators as potential host-directed treatments for influenza virus infection. The compounds reduced viral replication, inflammation, and reactive oxygen species by interfering with the export of viral RNA/protein complexes, independent of the NRF2 signaling pathway.
Article
Biochemistry & Molecular Biology
Sayaka Dantsuji, Mutsuhito Ohno, Ichiro Taniguchi
Summary: In eukaryotic cells, different classes of RNAs are exported to the cytoplasm by specific factors. Previous studies have shown that RNA polymerase II transcripts are classified based on their length, and hnRNP C is a key factor in this classification process. hnRNP C inhibits the recruitment of PHAX to long transcripts, but the mechanisms behind this inhibition are still unknown.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Microbiology
Thomas Kehrer, Anastasija Cupic, Chengjin Ye, Soner Yildiz, Mehdi Bouhaddou, Nicholas A. Crossland, Erika A. Barrall, Phillip Cohen, Anna Tseng, Tolga Cagatay, Raveen Rathnasinghe, Daniel Flores, Sonia Jangra, Fahmida Alam, Ignacio Mena, Sadaf Aslam, Anjali Saqi, Magdalena Rutkowska, Manisha R. Ummadi, Giuseppe Pisanelli, R. Blake Richardson, Ethan C. Veit, Jacqueline M. Fabius, Margaret Soucheray, Benjamin J. Polacco, Baran Ak, Arturo Marin, Matthew J. Evans, Danielle L. Swaney, Ana S. Gonzalez-Reiche, Emilia M. Sordillo, Harm van Bakel, Viviana Simon, Lorena Zuliani-Alvarez, Beatriz M. A. Fontoura, Brad R. Rosenberg, Nevan J. Krogan, Luis Martinez-Sobrido, Adolfo Garcia-Sastre, Lisa Miorin
Summary: The ORF6 protein of SARS-CoV-2 plays a crucial role in antagonizing the host's innate immunity by disrupting nuclear import and inhibiting cellular mRNA export. It also regulates viral protein expression. Mutations in ORF6 affect its interactions with host components and impair immune evasion in certain variants.
CELL HOST & MICROBE
(2023)
Article
Multidisciplinary Sciences
Liuke Sun, Huihui Kong, Mengmeng Yu, Zhenyu Zhang, Haili Zhang, Lei Na, Yuxing Qu, Yuan Zhang, Hualan Chen, Xiaojun Wang
Summary: Species differences in ANP32A/B restrict avian influenza virus in mammalian cells. Adaptive mutations, such as PB2-E627K, are required for efficient replication of avian influenza viruses in mammals. We found that NS2 protein promotes avian vRNP assembly and enhances interactions with mammalian ANP32A/B, overcoming the restriction. Disrupting the conserved SUMO-interacting motif (SIM) in NS2 impairs virus replication and pathogenicity in mammals, indicating NS2 as a cofactor in the adaptation process of avian influenza virus to mammals.
Article
Biochemistry & Molecular Biology
Yoav Lubelsky, Binyamin Zuckerman, Igor Ulitsky
Summary: The functions of long RNAs depend on their subcellular localization, but the identity of the sequences that dictate this localization and their high-resolution anatomy remain largely unknown. By using massively parallel RNA assays, the study identified the features within the SIRLOIN element and RNA-binding proteins that are required for its activity, providing a roadmap for high-throughput dissection of functional sequence elements in long RNAs.
Article
Multidisciplinary Sciences
Kelsey M. Haas, Michael J. Mcgregor, Mehdi Bouhaddou, Benjamin J. Polacco, Eun-Young Kim, Thong T. Nguyen, Billy W. Newton, Matthew Urbanowski, Heejin Kim, Michael A. P. Williams, Veronica V. Rezelj, Alexandra Hardy, Andrea Fossati, Erica J. Stevenson, Ellie Sukerman, Tiffany Kim, Sudhir Penugonda, Elena Moreno, Hannes Braberg, Yuan Zhou, Giorgi Metreveli, Bhavya Harjai, Tia A. Tummino, James E. Melnyk, Margaret Soucheray, Jyoti Batra, Lars Pache, Laura Martin-Sancho, Jared Carlson-Stevermer, Alexander S. Jureka, Christopher F. Basler, Kevan M. Shokat, Brian K. Shoichet, Leah P. Shriver, Jeffrey R. Johnson, Megan L. Shaw, Sumit K. Chanda, Dan M. Roden, Tonia C. Carter, Leah C. Kottyan, Rex L. Chisholm, Jennifer A. Pacheco, Maureen E. Smith, Steven J. Schrodi, Randy A. Albrecht, Marco Vignuzzi, Lorena Zuliani-Alvarez, Danielle L. Swaney, Manon Eckhardt, Steven M. Wolinsky, Kris M. White, Judd F. Hultquist, Robyn M. Kaake, Adolfo Garcia-Sastre, Nevan J. Krogan
Summary: This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. Key host proteins essential for IAV infection are revealed, and gene variants associated with severe influenza are discovered. Moreover, compounds targeting identified host factors suppress IAV replication and exhibit broad antiviral activity across influenza and coronavirus families.
NATURE COMMUNICATIONS
(2023)
Article
Virology
Ping Li, Han Ju, Ying Zhang, Jazmin Galvan Achi, Dongwei Kang, Jinmi Zou, Ruikun Du, Qinghua Cui, Xinyong Liu, Lijun Rong, Peng Zhan
Summary: Influenza viruses are a significant threat to public health globally. The emergence of drug-resistant strains has created the need for new antiviral drugs. In this study, a novel influenza virus inhibitor called A9, and its derivatives, were found to have broad-spectrum antiviral properties against influenza A and B viruses. Through various bioassays, it was shown that A9 inhibits the nuclear export of the viral ribonucleoprotein and specifically targets the nucleoprotein. These findings highlight A9 and its derivatives as potential leads for the treatment of influenza infections.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
James M. Burke, Alison R. Gilchrist, Sara L. Sawyer, Roy Parker
Summary: The study demonstrates that RNase L-mediated mRNA decay does not completely limit protein synthesis of dengue virus and influenza A virus, as their mRNAs largely escape this process. However, activation of RNase L inhibits nuclear mRNA export, thereby restricting influenza A virus protein synthesis and cytokine production.
Article
Microbiology
Julianna Han, Ketaki Ganti, Veeresh Kumar Sali, Carly Twigg, Yifeng Zhang, Senthamizharasi Manivasagam, Chieh-Yu Liang, Olivia A. Vogel, Iris Huang, Shanan N. Emmanuel, Jesse Plung, Lillianna Radoshevich, Jasmine T. Perez, Anice C. Lowen, Balaji Manicassamy
Summary: It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion, but the exact role of host factors in genome assembly is not fully understood. This study shows that Rab11a+ vesicles play a crucial role in the congregation and assembly of vRNPs, enabling specific genome assembly and production of infectious virus particles. However, in the absence of Rab11a, viral RNA segments fail to congregate properly, resulting in defects in virus assembly and increased production of non-infectious particles.
Article
Biochemistry & Molecular Biology
Rachel J. Hagey, Menashe Elazar, Edward A. Pham, Siqi Tian, Lily Ben-Avi, Claire Bernardin-Souibgui, Matthew F. Yee, Fernando R. Moreira, Meirav Vilan Rabinovitch, Rita M. Meganck, Benjamin Fram, Aimee Beck, Scott A. Gibson, Grace Lam, Josephine Devera, Wipapat Kladwang, Khanh Nguyen, Anming Xiong, Steven Schaffert, Talia Avisar, Ping Liu, Arjun Rustagi, Carl J. Fichtenbaum, Phillip S. Pang, Purvesh Khatri, Chien-Te Tseng, Jeffery K. Taubenberger, Catherine A. Blish, Brett L. Hurst, Timothy P. Sheahan, Rhiju Das, Jeffrey S. Glenn
Summary: By targeting conserved RNA secondary structures, researchers have discovered a potential therapeutic approach that can effectively treat multiple viruses and has shown good efficacy and resistance in experiments. These findings are important for antiviral prophylaxis and post-exposure therapy.
Article
Biology
Katina D. Hulme, Anjana C. Karawita, Cassandra Pegg, Myrna J. M. Bunte, Helle Bielefeldt-Ohmann, Conor J. Bloxham, Silvie Van den Hoecke, Yin Xiang Setoh, Bram Vrancken, Monique Spronken, Lauren E. Steele, Nathalie A. J. Verzele, Kyle R. Upton, Alexander A. Khromykh, Keng Yih Chew, Maria Sukkar, Simon Phipps, Kirsty R. Short
Summary: Influenza virus variants are more prevalent in pregnant and/or obese individuals due to their impaired interferon response. The non-allergic, paucigranulocytic subtype of asthma is associated with impaired type I interferon production, leading to increased disease severity and emergence of influenza virus variants in asthmatic mice. Asthmatic patients may be more susceptible to severe influenza and could potentially be a source of new influenza virus variants.
Article
Multidisciplinary Sciences
Franziska Guenl, Tim Krischuns, Julian A. Schreiber, Lea Henschel, Marius Wahrenburg, Hannes C. A. Drexler, Sebastian A. Leidel, Vlad Cojocaru, Guiscard Seebohm, Alexander Mellmann, Martin Schwemmle, Stephan Ludwig, Linda Brunotte
Summary: The replication of influenza A virus relies on ubiquitination of the viral polymerase derived from host cells. This study reveals that site-specific ubiquitination of PB1-K578 is acquired during infection and regulates the dimerization of polymerase and the binding of NP. Mass spectrometry analysis has identified 59 modified lysines across the three subunits of the viral polymerase, which affect mRNA transcription, vRNA replication, and the generation of recombinant viruses via non-proteolytic mechanisms.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Qiumei Wang, Heyou Yi, Yanchen Guo, Yankuo Sun, Zhiqing Yu, Lechen Lu, Ruirui Ye, Ermin Xie, Qianwen Wu, Yingwu Qiu, Weipeng Quan, Guihong Zhang, Heng Wang
Summary: This study investigates the potential role of proliferating cell nuclear antigen (PCNA) in PRRSV infection. The results show that PCNA is translocated from the nucleus to the cytoplasm after PRRSV infection. Furthermore, the interaction between N protein and PCNA affects PRRSV RNA synthesis. Therefore, PCNA could be a potential target for preventing and controlling PRRSV infection.
VETERINARY MICROBIOLOGY
(2023)
Article
Physiology
Othello Del Rosario, Karthik Suresh, Medha Kallem, Gayatri Singh, Anika Shah, Linda Zheng, Xin Yun, Nicolas M. Philip, Nirupama Putcha, Marni B. McClure, Haiyang Jiang, Franco D'Alessio, Meera Srivastava, Alakesh Bera, Larissa A. Shimoda, Michael Merchant, Madhavi J. Rane, Carolyn E. Machamer, Jason Mock, Robert Hagan, Abigail L. Koch, Naresh M. Punjabi, Todd M. Kolb, Mahendra Damarla
Summary: We found that mitogen-activated protein kinase-activated protein kinase 2 (MK2) plays a role in the nucleus translocation of caspase-3 during apoptosis. We investigated the kinase and nonkinase functions of MK2 in promoting this translocation and found that MK2 phosphorylates caspase-3. However, the phosphorylation of caspase-3 or MK2-dependent phosphorylation of caspase-3 did not affect caspase-3 activity. Instead, a nonenzymatic function of MK2, chaperoned nuclear trafficking, was required for caspase-3-mediated apoptosis. Our findings suggest that MK2 may act as a molecular switch in regulating the transition between the cytosolic and nuclear functions of caspase-3.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Article
Virology
Wiebke Obermann, Alexandra Friedrich, Ramakanth Madhugiri, Paul Klemm, Jan Philipp Mengel, Torsten Hain, Stephan Pleschka, Hans-Guido Wendel, Roland K. Hartmann, Susanne Schiffmann, John Ziebuhr, Christin Mueller, Arnold Gruenweller
Summary: Rocaglates are a class of broad-spectrum antiviral compounds that inhibit viral protein synthesis for different RNA viruses. They have differences in cytotoxicity against human immune cells, RNA-clamping efficiency, and antiviral activity. The results suggest that they have the potential to be effective antiviral drugs and are unlikely to lead to the emergence of viral escape mutations.
Article
Chemistry, Multidisciplinary
Akram Hegazy, Islam Mostafa, Yaseen A. M. M. Elshaier, Sara H. Mahmoud, Noura M. Abo Shama, Mahmoud Shehata, Galal Yahya, Nasr Fawzy Nasr, Ali M. El-Halawany, Mohamed Abdelalim Ali, Mohamed A. Ali, Mobarak Abu Mraheil, Assem M. El-Shazly, Ahmed Mostafa
Summary: Santonica flower extract shows promising anti-avian influenza activity and robust anti-human seasonal influenza activity, making it a potential natural antiviral agent.
Article
Virology
Georgios-Dimitrios Panagiotidis, Christin Mueller, Marco Binder, Friedemann Weber
Summary: The FDA-approved drug paliperidone has been found to inhibit the replication of influenza A virus by interfering with the binding of the polymerase subunit PB2 to the nucleoprotein NP. However, its effects are transient and limited to specific virus strains.
ARCHIVES OF VIROLOGY
(2023)
Article
Chemistry, Medicinal
Santo Previti, Roberta Ettari, Elsa Calcaterra, Salvatore Di Maro, Stefan J. Hammerschmidt, Christin Mueller, John Ziebuhr, Tanja Schirmeister, Sandro Cosconati, Maria Zappala
Summary: Despite progress in the development of vaccines and antivirals, the fight against SARS-CoV-2 and COVID-19 continues. Researchers have identified compounds that target the SARS-CoV-2 main protease, an essential viral enzyme, and have developed inhibitors with promising antiviral activity. These inhibitors also showed inhibitory effects on hCatL, a protein involved in viral entry into host cells. Some of these compounds demonstrated significant activity against SARS-CoV-2 in cell culture.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Zahra M. Alamshany, Reham R. Khattab, Nasser A. Hassan, Ahmed A. El-Sayed, Mohamed A. Tantawy, Ahmed Mostafa, Allam A. Hassan
Summary: A novel series of pyrido[2,3-d]pyrimidines, pyrido[3,2-e][1,3,4]triazolo, and tetrazolo[1,5-c]pyrimidines were synthesized and their structures were elucidated. Molecular docking analysis revealed that compounds 7c, 7d, and 7e exhibited promising antiviral activity against SARS-CoV-2 main protease M(pro) with lower IC50 values compared to the commonly used protease inhibitor Lopinavir. The in silico and in vitro results were consistent.
Article
Microbiology
David Scheibner, Ahmed H. Salaheldin, Ola Bagato, Luca M. Zaeck, Ahmed Mostafa, Ulrike Blohm, Christin Mueller, Ahmed F. Eweas, Kati Franzke, Axel Karger, Alexander Schaefer, Marcel Gischke, Donata Hoffmann, Solene Lerolle, Xuguang Li, Hatem S. Abd El-Hamid, Jutta Veits, Angele Breithaupt, Geert-Jan Boons, Mikhail Matrosovich, Stefan Finke, Stephan Pleschka, Thomas C. Mettenleiter, Robert P. de Vries, Elsayed M. Abdelwhab
Summary: Mutations in the neuraminidase (NA) of human H5N1 viruses play different roles in infection of mammals without affecting virulence or transmission in chickens. This study is important to understand the genetic determinants for replication of avian influenza viruses in mammals and should assist in the prediction of avian influenza viruses with zoonotic potential.
Article
Virology
Heiko Slanina, Ramakanth Madhugiri, Kai Wenk, Tess Reinke, Karin Schultheiss, Julia Schultheis, Nadja Karl, Uwe Linne, John Ziebuhr
Summary: The coronavirus replication-transcription complex (RTC) is essential for coronavirus genome replication and expression. The central functional subunit of RTC is nsp12, which contains the RNA-directed RNA polymerase (RdRp) domain and NiRAN domain. In this study, the NiRAN-mediated NMPylation activities of alpha- and betacoronaviruses were investigated and compared. The study revealed conserved properties of NiRAN domains, including robust NMPylation activities, nucleotide substrate preference, dependence on divalent metal ions, and the critical role of N-terminal residues for efficient NMPylation.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Bahaa A. Hemdan, Ahmed Mostafa, Marwa M. Elbatanony, Amal M. El-Feky, Tsvetelina Paunova-Krasteva, Stoyanka Stoitsova, Mohamed Azab El-Liethy, Gamila E. El-Taweel, Mobarak Abu Mraheil
Summary: The leaves of Azadirachta indica L. and Melia azedarach L. have medicinal benefits and exhibit antiviral and antibacterial activities. They showed robust anti-SARS-CoV-2 activity and exhibited broad-spectrum medicinal value.
Article
Virology
Felix Lehmann, Heiko Slanina, Martin Roderfeld, Elke Roeb, Jonel Trebicka, John Ziebuhr, Wolfram H. Gerlich, Christian G. Schuettler, Bernhard Schlevogt, Dieter Glebe
Summary: Chronic hepatitis B virus (HBV) infection is a global health threat. Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired.
Article
Microbiology
Amr A. Baiomy, Fathy E. Serry, Ashraf A. Kadry, Galal Yahya, Swapnil Doijad, Ahmed Mostafa, Mobarak Abu Mraheil, Amira M. El-Ganiny
Summary: This study conducted genomic analyses of Pseudomonas aeruginosa persister isolates from chronic human infections, revealing their low metabolic rates, multidrug tolerance, and strong biofilm-forming ability. Whole genome sequencing and phylogenetic analysis showed that these persister isolates belong to a distinct clade with a smaller genome size.
Review
Immunology
Ahlam Alasiri, Raya Soltane, Akram Hegazy, Ahmed Magdy Khalil, Sara H. Mahmoud, Ahmed A. Khalil, Luis Martinez-Sobrido, Ahmed Mostafa
Summary: Despite being widespread in wild birds and domestic poultry, human infections with highly pathogenic avian influenza H5Nx viruses have been limited since 1996. Few countries use vaccination as a control strategy, while most rely on culling infected flocks. China and Egypt are the major sites where vaccination has been employed, particularly for clade 2.3.4.4b H5N1 viruses. However, improper implementation of control strategies in Egypt has resulted in continuous outbreaks and virus evolution. Comprehensive surveillance in endemic areas is crucial to understand the public health risk of newly emerging immune-evasive or drug-resistant H5Nx variants.
Article
Microbiology
Yassmin Moatasim, Omnia Kutkat, Ahmed M. Osman, Mokhtar R. Gomaa, Faten Okda, Mohamed El Sayes, Mina Nabil Kamel, Mohamed Gaballah, Ahmed Mostafa, Rabeh El-Shesheny, Ghazi Kayali, Mohamed A. Ali, Ahmed Kandeil
Summary: The study found potential broad-spectrum inhibitory effects of Hydroxocobalamin and Methylcobalamin against three coronaviruses. Cyanocobalamin selectively affects SARS-CoV-2, while Methylcobalamin shows higher inhibition on SARS-CoV-2 compared to Hydroxocobalamin and Cyanocobalamin. These vitamins may have significant binding affinity to viral-specific cell receptors and proteins, suggesting potential benefits for coronavirus-infected patients.
Article
Biotechnology & Applied Microbiology
Ahmed Mostafa, Gomaa Mostafa-Hedeab, Hany Abdelfattah Elhady, Esraa Ahmed Mohamed, Abozer Y. Eledrdery, Sager Holyl Alruwaili, Ahmed Mohamed Al-Abd, Abdou Kamal Allayeh
Summary: EGCG, the most abundant polyphenol in green tea, has been shown to have significant antiviral activity against SARS-CoV-2 and HSV-2, as well as wound healing properties. It could potentially be a promising option for slowing down the course of acute cellular damage induced by systemic or topical viral infections.
JOURNAL OF GENETIC ENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Mina Nabil Kamel, Sara H. Mahmoud, Yassmin Moatasim, Ahmed El Taweel, Mahmoud Shehata, Mohamed Refaat Shehata, Elsayed Tarek AbdElSalam, Mohamed A. Ali, Ahmed Mostafa
Summary: Recent studies have shown the ability of seasonal influenza A/H1N1 and A/H3N2 viruses to exchange genetic segments, creating a novel H1N2 strain. A PR8-based H1N2 vaccine strain was generated, demonstrating effectiveness against both H1- and H3-type human influenza A viruses.
JOURNAL OF GENETIC ENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Asmaa Ezzat, Noura O. Abdelsamad, Amira A. Gamal, Mahmoud Shehata, Sara H. Mahmoud, Ahmed Mostafa, Mohamed A. Ali, Mona A. Esawy
Summary: This research investigated the effect of a probiotic polysaccharide, levan, in preventing COVID-19. Levans from Pseudomonas aeruginosa HI1 and Bacillus subtilis 9A showed the most promising results against COVID-19. These levans exhibited high tolerance to acidic, alkaline, bile salt, and H2O2 conditions. Hemolysis and antibiotic sensitivity tests confirmed the safety of the isolates. The ability of the isolates and their levans to adhere to lung cells may explain their ability to inhibit COVID-19 replication.
EGYPTIAN JOURNAL OF CHEMISTRY
(2022)