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.