An Integrated Approach to Identify Dual-Target Inhibitors for Nipah Virus Through Drug Repurposing

Principal Investigator:
Supratik Kar

Co-PIs:
Siyun Yang

Abstract:
Facing the rising menace of the Nipah virus (NiV), with its high mortality rate compare to COVID-19 and the risk of mutation-enhanced spread, this research highlights the critical need for effective treatments. By focusing on the NiV attachment glycoprotein-human ephrin-B2 and matrix protein, we aim to block viral entry and disrupt the assembly process. Leveraging DrugBank, we repurposed known small molecules, subjecting them to thorough screening via precision docking and ADMET profiling, followed by extensive 500ns molecular dynamics simulations and MM-GBSA assessments. Our findings pinpoint Iotrolan and Iodixanol as effective against both targeted proteins, while Rutin and Lactitol specifically combat the matrix protein.

Description of Research:
Facing the rising menace of the Nipah virus (NiV), with its high mortality rate compare to COVID-19 and the risk of mutation-enhanced spread, this research highlights the critical need for effective treatments. By focusing on the NiV attachment glycoprotein-human ephrin-B2 and matrix protein, we aim to block viral entry and disrupt the assembly process. Leveraging DrugBank, we repurposed known small molecules, subjecting them to thorough screening via precision docking and ADMET profiling, followed by extensive 500ns molecular dynamics simulations and MM-GBSA assessments. Our findings pinpoint Iotrolan (DB09487) and Iodixanol (DB01249) as effective against both targeted proteins, while Rutin (DB01698) and Lactitol (DB12942) specifically combat the matrix protein. Intriguingly, all molecules exhibit sugar-like structures, hinting at their glycomimetic potential to thwart NiV's glycosylation, potentially preventing host cell attachment or disrupting the viral lifecycle. Moreover, Iotrolan and Iodixanol feature nucleobase-like and amide components, suggesting they could hinder NiV replication by mimicking nucleotides. These results not only confirm the compounds' efficacy against NiV but also indicate their potential against other pathogens like SARS-CoV-2, thanks to their ability to target multiple proteins. This strategy, combining drug repurposing with computational analysis, accelerates the development of treatments for emerging viral challenges.