Dahiya Surbhi, Singh Sudhakar, Bhati Gaurav Kumar, Sehrawat Sharvan
Department of Biological Sciences, Indian Institute of Science Education and Research, Manauli, Punjab, India.
Immunohorizons. 2025 Mar 26;9(5). doi: 10.1093/immhor/vlaf012.
To alleviate the contribution of antibody dependent enhancement in DenV pathogenesis, we obtain a DenV neutralizing single domain antibody (sdAb) from an in-house constructed phage display library of camelid VHH. The anti-DenV sdAb specifically reacts with the envelope (E) protein of DenV with a Kd value of 2x108. Molecular dynamic simulations and docking analysis show that the sdAb interacts with the DenV(E) protein via domain II (EDII) and interferes with the virus internalization process. The anti-DenV(E) sdAb potently inhibits the infectivity of a DenV(E) protein expressing pseudovirus as well as that of a virulent DenV in vitro. A mouse adapted DenV2 induces 100% mortality in the infected IFNRKO mice, but the animals injected with the sdAb neutralized virus remain fully protected. Furthermore, the therapeutically administered anti-DenV(E) sdAb slows down the disease progression and enhances the survival of DenV infected animals. In conclusion, we report an anti-DenV(E) sdAb as a potential therapy to manage DenV pathogenesis.
为减轻抗体依赖性增强在登革病毒发病机制中的作用，我们从内部构建的骆驼科VHH噬菌体展示文库中获得了一种登革病毒中和单域抗体（sdAb）。抗登革病毒sdAb与登革病毒的包膜（E）蛋白特异性反应，解离常数（Kd）值为2×10⁻⁸。分子动力学模拟和对接分析表明，该sdAb通过结构域II（EDII）与登革病毒（E）蛋白相互作用，并干扰病毒内化过程。抗登革病毒（E）sdAb在体外能有效抑制表达登革病毒（E）蛋白的假病毒以及强毒株登革病毒的感染性。一种适应小鼠的登革病毒2型在感染的IFNRKO小鼠中可导致100%的死亡率，但注射了sdAb中和病毒的动物仍能得到完全保护。此外，经治疗性给药的抗登革病毒（E）sdAb可减缓疾病进展并提高登革病毒感染动物的存活率。总之，我们报道了一种抗登革病毒（E）sdAb作为控制登革病毒发病机制的潜在疗法。
