NU 2023-247
INVENTORS
SHORT DESCRIPTION
Computationally redesigned antibodies targeting SARS-CoV-2 for treating COVID-19.
BACKGROUND
The continuous evolution of SARS-CoV-2 has allowed the virus to escape most therapeutic neutralizing antibodies and vaccine-elicited immunity, contributing to millions of deaths worldwide. Traditional antibody development through experimental screening methods like phage display, ribosome display, and mammalian cell surface display is time-consuming and relatively low efficiency, creating urgent need for accelerated computational approaches to design broad-spectrum antibodies against fast-mutating pathogens that can respond rapidly to emerging variants before therapy resistance develops.
ABSTRACT
This invention describes novel antibodies against the SARS-CoV-2 receptor binding domain (RBD). Antibodies from convalescent patients were computationally redesigned using the physics-driven multistate protein design program iCFN to improve binding against Delta variant RBD without losing affinity for wild-type RBD. Experimental validation shows specific sequence substitutions achieved improved neutralization of Delta variant while maintaining wild-type activity. In vivo studies in K18-hACE2 transgenic mice demonstrate significant reductions in viral load, weight loss, clinical symptoms, acute lung inflammation, and hemorrhage/necrosis following Washington, Delta, and Omicron variant challenges.
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