Abstract
The dramatic experience with SARS-CoV-2 has alerted the scientific community to be ready to face new epidemics/pandemics caused by new variants. Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein have represented good drugs to interfere in the Spike/ Angiotensin Converting Enzyme-2 (ACE-2) interaction, preventing virus cell entry and subsequent infection, especially in patients with a defective immune system. We obtained, by an innovative phage display selection strategy, specific binders recognizing different epitopes of Spike. The novel human antibodies specifically bind to Spike-Receptor Binding Domain (RBD) in a nanomolar range and interfere in the interaction of Spike with the ACE-2 receptor. We report here that one of these mAbs, named D3, shows neutralizing activity for virus infection in cell cultures by different SARS-CoV-2 variants and retains the ability to recognize the Omicron-derived recombinant RBD differently from the antibodies Casirivimab or Imdevimab. Since anti-Spike mAbs, used individually, might be unable to block the virus cell entry especially in the case of resistant variants, we investigated the possibility to combine D3 with the antibody in clinical use Sotrovimab, and we found that they recognize distinct epitopes and show additive inhibitory effects on the interaction of Omicron-RBD with ACE-2 receptor. Thus, we propose to exploit these mAbs in combinatorial treatments to enhance their potential for both diagnostic and therapeutic applications in the current and future pandemic waves of coronavirus.
Keywords: Omicron variant; SARS-CoV-2; Spike-RBD/ACE-2; combinatorial treatments; neutralizing mAbs.
【저자키워드】 SARS-CoV-2, Omicron variant, Spike-RBD/ACE-2, combinatorial treatments, neutralizing mAbs., 【초록키워드】 coronavirus, pandemic, therapy, spike, antibody, spike glycoprotein, SARS-CoV-2 variant, Infection, diagnostic, SARS-CoV-2 virus, drug, immune system, omicron, monoclonal antibodies, virus, angiotensin converting enzyme, variants, ACE-2 receptor, Receptor binding domain, ACE-2, Epitopes, Neutralizing activity, Casirivimab, Imdevimab, RBD, Cell culture, therapeutic, Patient, Pandemics, Omicron variant, Neutralizing, Scientific community, glycoprotein, virus infection, epitope, mAbs, Sotrovimab, monoclonal, mAb, Interaction, angiotensin, Clinical use, cell entry, inhibitory effect, anti-spike MAbs, cell cultures, epidemics/pandemics, ENhance, caused, subsequent, investigated, recognize, interfere, recognizing, the Spike, combinatorial treatment, the antibody, 【제목키워드】 Human, Delta, Gamma, novel, mAb, Can,