Nipah virus (NiV) is a re-emerging zoonotic pathogen with a high mortality rate and no effective treatments, prompting the search for new antiviral strategies. While conventional antiviral drugs are often limited by issues such as poor specificity, off-target effects, and resistance development, nanobodies offer distinct advantages. These small, single-domain antibodies exhibit high specificity and stability, making them ideal candidates for antiviral therapy. The NiV fusion protein (NiVF) is a crucial target for nanobodies due to its vital role in infection. Thus, we aimed to design a high affinity nanobody targeting NiVF using computational methods. Molecular docking identified the lead NB with the highest binding energy to NiVF. The complementarity determining regions (CDRs) of the lead NB underwent two rounds of in silico site-directed mutagenesis generating a high-affinity engineered NB. Subsequent re-docking, molecular dynamics (MD) simulations, and various in silico evaluations, of the selected engineered NB-NiVF complex were performed. After mutations, results showed that the lead (native) NB, initially with a binding energy of -85.2 kcal.mol, was optimized to an engineered NB with a higher binding energy of -99.65 kcal.mol. Additionally, the engineered NB has more favorable physicochemical properties, exhibited a more stable (in a 200-ns MD simulation) and stronger molecular interactions than the native NB, suggesting a favorable mutation and enhancement of the potential neutralization activity of the engineered NB. This study highlights the use of computational methods to design an optimized high-affinity NB and the potential of NB-based antivirals against NiV, necessitating further experimental validation.
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http://dx.doi.org/10.1016/j.compbiolchem.2025.108354 | DOI Listing |
Pharmacol Res
January 2025
Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China. Electronic address:
The necrosis of pancreatic acinar cells is a key molecular event in the progression of acute pancreatitis (AP), with disturbances in mitochondrial energy metabolism considered to be a direct causative factor of acinar cell necrosis. Histidine triad nucleotide-binding protein 2 (HINT2) has been implicated in the development of various diseases, whereas its involvement in the progression of AP remains unclear. This study aims to investigate the role of HINT2 in AP.
View Article and Find Full Text PDFMicrob Pathog
January 2025
Postgraduate Program in Biological Sciences (PPGCB), Federal University of Pernambuco (UFPE), Recife 50670-901, PE, Brazil. Electronic address:
The NorA and TetK efflux pumps mediate resistance to fluoroquinolone and tetracycline antibiotics by actively extruding these compounds and reducing their intracellular concentrations. Consequently, intense research has focused on inhibiting these efflux mechanisms using antimicrobial agents derived from natural or synthetic sources. This study used Fourier transform infrared spectroscopy (ATR-FTIR) to analyze the various functional groups present in p-coumaric acid.
View Article and Find Full Text PDFComput Biol Chem
January 2025
Virology and Vaccine Research and Development Program, Department of Science and Technology-Industrial Technology Development Institute, Taguig City, Metro Manila 1631, Philippines; S&T Fellows Program, Department of Science and Technology, Taguig City, Metro Manila 1631, Philippines; Department of Biology, College of Arts and Sciences, University of the Philippines - Manila, Metro Manila 1000, Philippines. Electronic address:
Nipah virus (NiV) is a re-emerging zoonotic pathogen with a high mortality rate and no effective treatments, prompting the search for new antiviral strategies. While conventional antiviral drugs are often limited by issues such as poor specificity, off-target effects, and resistance development, nanobodies offer distinct advantages. These small, single-domain antibodies exhibit high specificity and stability, making them ideal candidates for antiviral therapy.
View Article and Find Full Text PDFSci Total Environ
January 2025
State Key Laboratory of Marine Environmental Science/College of the Environment and Ecology, Xiamen University, Xiamen 361005, China; Key Laboratory of Marine Ecology & Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. Electronic address:
Understanding metabolic activities involved in bloom formation during a single-species algal bloom has improved greatly. However, little is known about metabolic activities during a multi-species algal bloom. Here, we investigated protein expression profiles at different bloom stages of a mixed dinoflagellate bloom caused by Karenia mikimotoi and Prorocentrum obtusidens (syn.
View Article and Find Full Text PDFComput Methods Programs Biomed
January 2025
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, 141-83 Stockholm, Sweden. Electronic address:
Background And Objective: Myeloid-derived suppressor cells (MDSCs) are a crucial and diverse group of cells found in the tumor microenvironment (TME) that facilitate progression, invasion, and metastasis within solid tumors. CD84, a homophilic adhesion molecule expressed on MDSCs, plays a critical role in their accumulation and function within the TME. This study aims to investigate the protein-protein interactions of CD84 using molecular dynamics simulations and to explore potential therapeutic strategies targeting these interactions.
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