Abstract
Most therapeutic mAbs target the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Unfortunately, the RBD is a hot spot for mutations in SARS-CoV-2 variants, which will lead to loss of the neutralizing function of current therapeutic mAbs. Universal mAbs for different variants are necessary. We identified mAbs that recognized the S2 region of the spike protein, which is identical in different variants. The mAbs could neutralize SARS-CoV-2 infection and protect animals from SARS-CoV-2 challenge. After cloning the variable region of the light chain and heavy chain, the variable region sequences were humanized to select a high-affinity humanized mAb, hMab5.17. hMab5.17 protected animals from SARS-CoV-2 challenge and neutralized SARS-CoV-2 variant infection. We further identified the linear epitope of the mAb, which is not mutated in any variant of concern. These data suggest that a mAb recognizing the S2 region of the spike protein will be a potential universal therapeutic mAb for COVID-19.
Keywords: COVID-19; Drug therapy; Therapeutics.
【저자키워드】 COVID-19, Therapeutics, drug therapy, 【초록키워드】 SARS-CoV-2, Mutation, Therapeutics, SARS-COV-2 infection, variant, SARS-CoV-2 variant, Infection, drug, variants, drug therapy, Spike protein, Receptor-binding domain, SARS-CoV-2 variants, animals, RBD, therapeutic, hot spot, epitope, mAbs, mAb, lead, heavy chain, light chain, variable region, These data, sequence, MOST, neutralizing function, humanized, neutralize, neutralized, PROTECT, linear, the spike protein, the RBD, the receptor-binding domain, mutated, recognizing, Universal, 【제목키워드】 antibody, viral variant, conserved, overcome, the SARS-CoV-2,