NU 2023-247

INVENTORS

• Huiping Liu*
• Deyu Fang*
• Hannah Mubarak
• Andrew Hoffmann
• Nurmaa Dashzeveg
• Lamiaa El-Shennawy
• Juncheng Wei
• Wuwei Tan
• Yang Shen

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.

APPLICATIONS

• Treatment and prophylaxis of COVID-19 caused by SARS-CoV-2 variants, especially for immunocompromised patients who cannot mount an adequate vaccine response.
• Convalescent plasma enhancement and antibody cocktail development to provide broader protection against immune escape.

ADVANTAGES

• Maintained wild-type neutralization while gaining variant efficacy

PUBLICATIONS

• Almubarak et al. Integrated antibody language model accelerates IgG screening and design for broad-spectrum antiviral therapy. iScience. 28 (10): 113584 (2025).

IP STATUS

• US patent application US20250230222A1 has been filed