Alphaviruses such as Chikungunya virus (CHIKV), O'Nyong-Nyong virus (ONNV), Ross River virus (RRV), Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), and Western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that can cause fevers, rash, and rheumatic diseases (CHIKV, ONNV, RRV) or potentially fatal encephalitis (EEEV, VEEV, WEEV) in humans. These diseases are considered neglected tropical diseases for which there are no current antiviral therapies or vaccines available. The alphavirus non-structural protein 2 (nsP2) contains a papain-like protease, which is considered to be a promising target for antiviral drug discovery. In this work, molecular docking analyses have been carried out on a library of 2174 plant-derived natural products (290 alkaloids, 664 terpenoids, 1060 polyphenolics, and 160 miscellaneous phytochemicals) with the nsP2 proteases of CHIKV, ONNV, RRV, EEEV, VEEV, WEEV, as well as Aura virus (AURV), Barmah Forest Virus (BFV), Semliki Forest virus (SFV), and Sindbis virus (SINV) in order to identity structural scaffolds for inhibitor design or discovery. Of the 2174 phytochemicals examined, a total of 127 showed promising docking affinities and poses to one or more of the nsP2 proteases, and this knowledge can be used to guide experimental investigation of potential inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.compbiolchem.2016.06.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells.
Mol Biol Cell
January 2025
Institute for Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
Tetraspanins (Tspans) are transmembrane proteins that coordinate life cycle steps of viruses from distinct families. Here, we identify the human Tspan10 and Tspan15, both members of the TspanC8 subfamily, as replication factors for alphavirus Venezuelan equine encephalitis virus (VEEV) in astrocytoma cells. Pharmacological inhibition and siRNA-mediated silencing of TspanC8 interactor a disintegrin and metalloproteinase 10 (ADAM10) reduced VEEV infection.
View Article and Find Full Text PDFCombining computational modeling and experimental library screening to affinity-mature VEEV-neutralizing antibody F5.
Protein Sci
February 2025
Department of Biotechnology and Bioengineering, Sandia National Laboratories, Livermore, California, USA.
Engineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand-up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of F5, a monoclonal antibody with potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), to recombinant VEEV (IAB) E1E2 antigen.
View Article and Find Full Text PDFThe weight of multiple hits: how TBI and infectious encephalitis co-modulate adverse outcomes.
Brain Inj
January 2025
Department of Biomedical Science and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, USA.
Background: Chronic neurologic deficits from traumatic brain injury (TBI) and subsequent infectious encephalitis are poorly characterized.
Methods: Using TriNetX database we queried patients 18 years or older with a confirmed diagnosis of encephalitis between 2016 and 2024. Patient cohorts included those with a diagnosis of TBI at least one month before encephalitis ( = 1,038), those with a diagnosis of a TBI anytime before encephalitis ( = 1,886), and those with encephalitis but no TBI, ( = 45,210; = 45,215).
Research progress of mosquito-borne virus mRNA vaccines.
Mol Ther Methods Clin Dev
March 2025
Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory for Research on Prevention and Treatment of Tropical Diseases, Beijing, China.
In recent years, mRNA vaccines have emerged as a leading technology for preventing infectious diseases due to their rapid development and high immunogenicity. These vaccines encode viral antigens, which are translated into antigenic proteins within host cells, inducing both humoral and cellular immune responses. This review systematically examines the progress in mRNA vaccine research for major mosquito-borne viruses, including dengue virus, Zika virus, Japanese encephalitis virus, Chikungunya virus, yellow fever virus, Rift Valley fever virus, and Venezuelan equine encephalitis virus.
View Article and Find Full Text PDFMolecular basis for shifted receptor recognition by an encephalitic arbovirus.
bioRxiv
January 2025
Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!