Article
Virology
Michelle Felicia Lee, Mohd Ishtiaq Anasir, Chit Laa Poh
Summary: Dengue infections pose a critical threat to public health worldwide, and there is an urgent need to develop effective antivirals. Peptides designed to target the DENV envelope protein show promise as antiviral candidates. Among the twelve peptides designed, four exhibited potent inhibitory effects against multiple DENV serotypes. Peptide 3 demonstrated the best overall antiviral activity, while peptide 5F showed particular efficacy against DENV-4 during post-infection treatment.
Article
Cell Biology
Sundy N. Y. Yang, Belinda Maher, Chunxiao Wang, Kylie M. Wagstaff, Johanna E. Fraser, David A. Jans
Summary: This study identifies two drugs that can inhibit the replication of dengue virus and other flaviviruses by directly binding to a viral protein.
Article
Chemistry, Multidisciplinary
Leidy L. Garcia-Ariza, Cristian Rocha-Roa, Leonardo Padilla-Sanabria, Jhon C. Castano-Osorio
Summary: This study aims to search for drug-like compounds that can inhibit the NS5 protein of dengue virus. Through virtual screening, 18 compounds were identified that can bind to NS5, with the best compounds highlighted in the methyltransferase and RNA-dependent RNA polymerase domains. These compounds interact with amino acids at catalytic sites and have promising physicochemical and pharmacological properties.
FRONTIERS IN CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Yunzheng Yan, Jingjing Yang, Dian Xiao, Jiye Yin, Mengwen Song, Yijie Xu, Lei Zhao, Qingsong Dai, Yuexiang Li, Cui Wang, Zhuang Wang, Xiaofeng Ren, Xiaotong Yang, Jie Ni, Miaomiao Liu, Xiaojia Guo, Wei Li, Xingjuan Chen, Zhiqiang Liu, Ruiyuan Cao, Wu Zhong
Summary: This study found that Nafamostat (NM) has the potential to inhibit flavivirus infections. Through in vitro and in vivo experiments, researchers found that NM effectively inhibits the replication of Zika virus and other flaviviruses. Further research revealed the antiviral mechanism of NM and proposed a novel drug design approach targeting the flavivirus envelope protein.
ANTIVIRAL RESEARCH
(2022)
Article
Virology
Alexander Malogolovkin, Andrew Davies, Sherif Abouelhadid, Adeline Kerviel, Polly Roy, Andrew K. Falconar
Summary: Researchers constructed and characterized Zika virus-like particles (Zika VLPs) to study the interaction between ZIKV and antibodies. These VLPs showed typical virus morphology and the importance of glycosylation of the E glycoprotein was demonstrated. A new construct showed higher efficacy and protein concentration, making it a potential candidate for vaccine trials.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Virology
Szu-Chia Hsieh, Wen-Yang Tsai, Jih-Jin Tsai, Mars Stone, Graham Simmons, Michael P. Busch, Marion Lanteri, Susan L. Stramer, Angel Balmaseda, Eva Harris, Wei-Kung Wang
Summary: The study highlights the need for better serological tests to distinguish past ZIKV, DENV, and other flavivirus infections, and improve vaccine strategies in endemic regions where interactions between these viruses are critical.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Mafalda A. Farelo, Despoina Korrou-Karava, Katrina F. Brooks, Tiffany A. Russell, Kevin Maringer, Peter U. Mayerhofer
Summary: Flaviviruses such as dengue virus and Zika virus use the host protein PEX19 to downregulate peroxisomes, which results in reduced interferon production. However, unlike cellular peroxisomal membrane proteins, the viral proteins do not localize to peroxisomes. Furthermore, the presence of viral proteins leads to impaired peroxisomal biogenesis through a PEX19-independent mechanism. This challenges the current understanding of how flaviviruses manipulate peroxisomal abundance and suggests an unknown role of peroxisomes in viral biology.
Review
Pharmacology & Pharmacy
Ivo C. C. Martins, Rafaela C. C. Ricardo, Nuno C. C. Santos
Summary: Dengue, West Nile, and Zika viruses are vector-borne flaviviruses that cause disease outbreaks with potentially severe symptoms and socioeconomic repercussions. Currently, there are no specific treatments available, and only generic symptom relief is possible. The effectiveness of the first dengue vaccine, Dengvaxia, is limited. Prophylactic approaches against other viruses are even more restricted. Therefore, there is a need for therapeutic strategies.
Article
Microbiology
Seydou Ka, Natacha Merindol, Aissatou Aicha Sow, Amita Singh, Karima Landelouci, Melodie B. Plourde, Genevieve Pepin, Marco Masi, Roberta Di Lecce, Antonio Evidente, Matar Seck, Lionel Berthoux, Laurent Chatel-Chaix, Isabel Desgagne-Penix
Summary: The study found that Amaryllidaceae alkaloids (AAs) from plants of the Amaryllidaceae family have strong antiviral activity, with cherylline specifically inhibiting dengue virus and Zika virus replication. This suggests that AAs, including cherylline, could be a potential source of new antiviral drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Facundo N. Gallo, Ana G. Enderle, Lucas A. Pardo, Emilse S. Leal, Mariela Bollini
Summary: Dengue virus is a major challenge in public health, and there is currently no effective antiviral treatment. Control strategies focused on vector control have been unsuccessful, and the virus has become endemic in over 100 countries. This review provides an overview of potential antiviral agents that target the entry of the virus into host cells, discussing their development and evaluation.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Muhammad Usman Mirza, Ida Alanko, Michiel Vanmeert, Kendall M. Muzzarelli, Outi M. H. Salo-Ahen, Iskandar Abdullah, Iulia A. Kovari, Sandra Claes, Steven De Jonghe, Dominique Schols, Raymond F. Schinazi, Ladislau C. Kovari, John F. Trant, Sarfraz Ahmad, Matheus Froeyen
Summary: This study used a computer-aided structure-based approach to screen a library of compounds against ZIKV NS2B-NS3 protease. Several compounds showed promising activity against the protease, and one compound also exhibited anti-ZIKV activity in whole cells. This research provides a promising starting point for the development of novel compounds against ZIKV.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Microbiology
Maikke B. Ohlson, Jennifer L. Eitson, Alexandra I. Wells, Ashwani Kumar, Seoyeon Jang, Chunyang Ni, Chao Xing, Michael Buszczak, John W. Schoggins
Summary: Viruses rely on host ribosomes for protein synthesis, but the specific factors involved in translation of viral RNAs are not fully understood. Through a CRISPR screen, researchers identified multiple host factors, including 60S ribosome biogenesis proteins, that are required for viral protein synthesis. In addition, the study revealed the importance of SBDS and SPATA5 in viral replication for a wide range of viruses.
Review
Immunology
Qingxin Li, Congbao Kang
Summary: This article summarizes the recent studies on the dengue NS4B protein. The NS4B membrane protein has been validated as a target for drug discovery, and several NS4B inhibitors have shown antiviral activities. Although the atomic structure of NS4B has not been obtained, cell-based assays play an important role in developing inhibitors.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Guntur Fibriansah, Elisa X. Y. Lim, Jan K. Marzinek, Thiam-Seng Ng, Joanne L. Tan, Roland G. Huber, Xin-Ni Lim, Valerie S. Y. Chew, Victor A. Kostyuchenko, Jian Shi, Ganesh S. Anand, Peter J. Bond, James E. Crowe, Shee-Mei Lok
Summary: Dengue virus has four serotypes (DENV1-4) with different strains within each serotype. The virus can exhibit smooth or bumpy surface morphologies at 37 degrees C, depending on the strain. High-affinity therapeutic antibodies are able to neutralize diverse morphologies of dengue virus.
Article
Biochemistry & Molecular Biology
Jose Villalain
Summary: Flaviviruses, including dengue and yellow fever, enter host cells through membrane fusion mediated by envelope E protein. Our study reveals that besides the fusion peptide, other segments of the envelope E protein are involved in the fusion process, suggesting a potential target for antiviral drug development against DENV and flaviviruses.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Biochemistry & Molecular Biology
Madhulata Kumari, Mohd Waseem, Naidu Subbarao
Summary: In this study, a ligand-based scaffold model was generated to identify multi-targeting inhibitors as potential antitubercular agents. Through molecular docking and molecular dynamics simulations, compound HPT was identified as a potent anti-mycobacterial inhibitor with good binding affinity to multiple mur enzymes of Mtb. This computational study provides a lead scaffold based on 5'-O-(5-Amino-5-deoxy-beta-D-ribofuranosyl)uridine for the development of more effective pharmaceutical molecules targeting multiple mur enzymes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Jyoti Verma, Naidu Subbarao
Summary: This study identified two essential target binding sites on the CHIKV E1-E2 proteins and used high throughput computational screening to identify potential small molecule protein-protein interaction (PPI) modulators. Molecular dynamics simulations and binding free energy calculations confirmed the stability of three compounds at the predicted interface binding sites. The findings suggest that these small molecule inhibitors have the potential to block the receptor interaction of CHIKV and could serve as templates for designing anti-CHIKV drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Mohd Waseem, Jitendra K. Thakur, Naidu Subbarao
Summary: In this study, a large number of small molecules were screened to find novel and potential inhibitors of LDM. Two best candidates, C1 and C3, were selected and validated through molecular dynamic simulation. Results showed that C1 and C3 have higher binding affinity with LDM compared to the benchmark compound, suggesting their potential as significant LDM inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Govinda Rao Dabburu, Aakriti Jain, Naidu Subbarao, Manish Kumar
Summary: Malaria is a major global concern, particularly in Africa. The resistance to current antimalarial drugs is a growing problem. In this study, potential dual inhibitors of two important enzymes involved in the haemoglobin degradation pathway of Plasmodium falciparum were identified using in-silico molecular docking and simulation techniques. These novel dual inhibitors may have better efficacy than existing antimalarial drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Gastroenterology & Hepatology
Le Tao, Guangyue Yang, Tiantian Sun, Jie Tao, Chan Zhu, Huimin Yu, Yalan Cheng, Zongguo Yang, Mingyi Xu, Yuefeng Jiang, Wei Zhang, Zhiyi Wang, Wenting Ma, Liu Wu, Dongying Xue, Dongxue Wang, Wentao Yang, Yongjuan Zhao, Shane Horsefield, Bostjan Kobe, Zhe Zhang, Zongxiang Tang, Qigen Li, Qiwei Zhai, Steven Dooley, Ekihiro Seki, Ping Liu, Jianrong Xu, Hongzhuan Chen, Cheng Liu
Summary: This study discovered the presence of TRPV1 in hepatic stellate cells (HSCs) and investigated its function in this cell type and liver fibrosis. TRPV1's expression is associated with liver fibrosis and its antifibrotic properties are attributed to the prevention of HSC activation. This finding could be a potential therapeutic strategy against liver fibrosis.
JOURNAL OF HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shrivaishnavi Ranganathan, Deepa Sethi, Sandhya Kasivisweswaran, L. Ramya, Richa Priyadarshini, Ragothaman M. Yennamalli
Summary: This study presents a computational model and experimental evidence of the ars gene cluster in Deinococcus indicus DR1, revealing its role and regulation in arsenic resistance. The proteins in this cluster are involved in transcriptional regulation and reduction reactions to facilitate arsenic extrusion. This structural characterization study provides valuable insights into the mechanism of arsenic tolerance in Deinococcus indicus DR1.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Plant Sciences
Natsumi Maruta, Mitchell Sorbello, Bryan Y. J. Lim, Helen Y. McGuinness, Yun Shi, Thomas Ve, Bostjan Kobe
Summary: TIR domains are widely present in archaea, bacteria, and eukaryotes, often associated with immune functions. In plants, they are found in several proteins, including NLRs, NLR-like proteins, and TIR-only proteins. They are also found in effector proteins from phytopathogenic bacteria that suppress host immunity. TIR domains in plants and bacteria act as enzymes, cleaving NAD+ and other nucleotides. In dicot plants, TIR-derived signaling molecules activate downstream immune signaling proteins, EDS1 family proteins, and helper NLRs. Recent research has provided significant insights into the mechanism and signaling pathway of TIR domains.
CURRENT OPINION IN PLANT BIOLOGY
(2023)
Article
Chemistry, Medicinal
Madhulata Kumari, Naidu Subbarao
Summary: The aim of this study was to develop a one-dimensional convolutional neural network-based quantitative structure-activity relationship (1D-CNN-QSAR) model for identifying novel anthrax inhibitors and analyzing chemical space. The 1D-CNN-QSAR model showed a mean square error of 0.045 and a predicted correlation coefficient of 0.79 for the test set. Chemical space analysis revealed high fragment pair similarity and identified specific fragments associated with activity cliffs. These findings provide a basis for developing potent novel drug candidates for anthrax using the proposed model and fingerprint analysis.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Srividhya Krishnan, Krishnakant Gupta, Subramaniyasharma Sivaraman, Ponnusami Venkatachalam, Ragothaman M. M. Yennamalli, Saravanan Ramiah Shanmugam
Summary: We investigated the Thioredoxin reductase (Trr1) from Cryptococcus neoformans as a gene target for the development of novel antifungal agents. Trr1 plays a vital role in the survival of C. neoformans in the oxidative environment of macrophages and is crucial for its virulence. We analyzed the aqueous phase obtained from the pyrolysis of Parthenium hysterophorus biomass and found it to be rich in potential antifungal aromatic and organic compounds. Through virtual screening and molecular dynamics simulation, we identified 2,4-Di-tertbutyl phenol and 1H-Pyrazole, 4-ethyl-3,5-dimethyl as potent antifungal agents against Trr1 of C. neoformans.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Geet Madhukar, Naidu Subbarao
Summary: Among the major altered pathways in head and neck squamous cell carcinoma, the AKT/mTORC1/S6K and NRF2/KEAP1 pathways are significant and promising candidates for cancer therapeutics due to their overexpression and overstimulation of proteins. This study aimed to explore S6K2 and NRF2 as potential targets and identified natural compounds Crocin and Gypenoside XVII against S6K2, and Chebulinic acid and Sennoside A against NRF2. The findings provide insights into the pathways and can contribute to the development of therapeutics against head and neck squamous cell carcinoma.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Adam M. Bayless, Sisi Chen, Sam C. Ogden, Xiaoyan Xu, John D. Sidda, Mohammad K. Manik, Sulin Li, Bostjan Kobe, Thomas Ve, Lijiang Song, Murray Grant, Li Wan, Marc T. Nishimura
Summary: TIR domain proteins play important roles in cell death and immunity. Both plants and bacteria use TIR domains to produce cADPR isomers as potential immune signaling molecules. This study demonstrates the conservation and functional overlap of cADPR isomers produced by plant and prokaryotic TIRs, and clarifies the activation mechanism of the Thoeris system by plant TIRs. The findings highlight the distinct signaling requirements and diversity of small-molecule products generated by TIRs across kingdoms.
Article
Biochemistry & Molecular Biology
Adity Raturi, Vikas Yadav, Nasimul Hoda, Naidu Subbarao, Saif Ali Chaudhry
Summary: Alzheimer's disease is a prevalent and neurodegenerative disorder with a complex pathophysiology. Polypharmacological drug profiles have emerged as a strategy in drug development to enhance therapeutic efficacy. In vitro study found that certain colchicine derivative compounds showed promising binding interactions with AD-related targets, indicating their potential as anti-inflammatory, antioxidant, anti-neurodegenerative and neuroprotective agents against Alzheimer's and other neurodegenerative diseases.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Microbiology
Zinnat Shahina, Ragothaman M. Yennamalli, Tanya E. S. Dahms
Summary: This study examines the effects of four plant-derived essential oil components on Candida albicans. The essential oil components disrupt the localization of the kinesin motor protein Kar3 and microtubules, leading to hyphal and biofilm defects.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Shricharan Senthilkumar, Sankar Mahesh, Subachandran Jaisankar, Ragothaman M. Yennamalli
Summary: This study analyzed the proteomes of thermophilic and mesophilic fungi and found that thermophilic fungi have more charged and exposed residues, which may contribute to their thermostability.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Jyoti Verma, Pragyan Parimita Rath, Samudrala Gourinath, Naidu Subbarao
Summary: This study identified potential inhibitors targeting the receptor binding domain of the S protein of SARS-CoV-2 through computational and experimental techniques. Experimental evidence showed that several molecules have high binding affinity towards the S-RBD. Molecular dynamics simulation indicated the binding stability of these inhibitors, suggesting the possibility of interfering with ACE2 binding.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)