Optimization of Bangladesh and Malaysian genotype recombinant reporter Nipah viruses for in vitro antiviral screening and in vivo disease modeling

作者：Michael K. Lo, Shilpi Jain, Katherine Davies, Teresa E. Sorvillo, Stephen R. Welch, JoAnn D. Coleman-McCray, Payel Chatterjee, Anne L. Hotard, Troy O'Neal, Mike Flint, Hui‐wang Ai, César G. Albariño, Jessica R. Spengler, Joel M. Montgomery, Christina F. Spiropoulou · 发表于：Antiviral Research · 年份：2024 · DOI：10.1016/j.antiviral.2024.106013 · 被引用次数：10 · 研究领域：Virology and Viral Diseases、Viral Infections and Vectors、Mosquito-borne diseases and control

Nipah virus (NiV) causes near-annual outbreaks of fatal encephalitis and respiratory disease in South Asia with a high mortality rate (∼70%). Since there are no approved therapeutics for NiV disease in humans, the WHO has designated NiV and henipaviral diseases priority pathogens for research and development. We generated a new recombinant green fluorescent reporter NiV of the circulating Bangladesh genotype (rNiV-B-ZsG) and optimized it alongside our previously generated Malaysian genotype reporter counterpart (rNiV-M-ZsG) for antiviral screening in primary-like human respiratory cell types. Validating our platform for rNiV-B-ZsG with a synthetic compound library directed against viral RNA-dependent RNA polymerases, we identified a hit compound and confirmed its sub-micromolar activity against wild-type NiV, green fluorescent reporter, and the newly constructed bioluminescent red fluorescent double reporter (rNiV-B-BREP) NiV. We furthermore demonstrated that rNiV-B-ZsG and rNiV-B-BREP viruses showed pathogenicity comparable to wild-type NiV-B in the Syrian golden hamster model of disease, supporting additional use of these tools for both pathogenesis and advanced pre-clinical studies in vivo . • Recombinant Nipah viruses expressing ZsGreen and BREP are suitable for antiviral screening. • Library screening against rNiV-B-ZsG identified a hit compound with sub micromolar potency. • rNiV-B-ZsG and rNiV-B-BREP reporter viruses retain wild-type pathogenicity in Syrian hamsters.