Development of Fusion-Based Assay as a Drug Screening Platform for Nipah Virus Utilizing Baculovirus Expression Vector System.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Nipah Virus*/genetics ; Nipah Virus*/drug effects ; Baculoviridae*/genetics ; Giant Cells*/drug effects ; Giant Cells*/metabolism ; Giant Cells*/virology ; Drug Evaluation, Preclinical*/methods; Animals ; Humans ; Genetic Vectors/genetics ; Antiviral Agents/pharmacology ; Suramin/pharmacology ; Ephrin-B2/metabolism ; Ephrin-B2/genetics ; Henipavirus Infections/virology ; Sf9 Cells ; Viral Fusion Proteins/genetics ; Viral Fusion Proteins/metabolism ; Virus Internalization/drug effects

Nipah virus (NiV) is known to be a highly pathogenic zoonotic virus, which is included in the World Health Organization Research & Development Blueprint list of priority diseases with up to 70% mortality rate. Due to its high pathogenicity and outbreak potency, a therapeutic countermeasure against NiV is urgently needed. As NiV needs to be handled within a Biological Safety Level (BSL) 4 facility, we had developed a safe drug screening platform utilizing a baculovirus expression vector system (BEVS) based on a NiV-induced syncytium formation that could be handled within a BSL-1 facility. To reconstruct the NiV-induced syncytium formation in BEVS, two baculoviruses were generated to express recombinant proteins that are responsible for inducing the syncytium formation, including one baculovirus exhibiting co-expressed NiV fusion protein (NiV-F) and NiV attachment glycoprotein (NiV-G) and another exhibiting human EphrinB2 protein. Interestingly, syncytium formation was observed in infected insect cells when the medium was modified to have a lower pH level and supplemented with cholesterol. Fusion inhibitory properties of several compounds, such as phytochemicals and a polysulfonated naphthylamine compound, were evaluated using this platform. Among these compounds, suramin showed the highest fusion inhibitory activity against NiV-induced syncytium in the baculovirus expression system. Moreover, our in silico results provide a molecular-level glimpse of suramin's interaction with NiV-G's central hole and EphrinB2's G-H loop, which could be the possible reason for its fusion inhibitory activity.

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Keywords: MMGBSA; Nipah virus; baculovirus expression vector system; docking; fusion inhibitor; suramin; syncytium

0 (Antiviral Agents)
6032D45BEM (Suramin)
0 (Ephrin-B2)
0 (Viral Fusion Proteins)

Date Created: 20240829 Date Completed: 20240829 Latest Revision: 20240903

20240903

PMC11354753

10.3390/ijms25169102

39201788