Potent antibodies against immune invasive SARS-CoV-2 Omicron subvariants

The development of neutralizing antibodies (nAbs) is an important strategy to tackle the Omicron variant. Omicron N-terminal domain (NTD) mutations including A67V, G142D, and N212I alter the antigenic structure, and mutations in the spike (S) receptor binding domain (RBD), such as N501Y, R346K, and T478K enhance affinity between the RBD and angiotensin-converting enzyme 2 (ACE2), thus conferring Omicron powerful immune evasion. Most nAbs (COV2-2130, ZCB11, REGN10933) and combinations of nAbs (COV2-2196 + COV2-2130, REGN10933 + REGN10987, Brii-196 + Brii-198) have either greatly reduced or lost their neutralizing ability against Omicron, but several nAbs such as SA55, SA58, S309, LY-CoV1404 are still effective in neutralizing most Omicron subvariants. This paper focuses on Omicron subvariants mutations and mechanisms of current therapeutic antibodies that remain efficacious against Omicron subvariants, which will guide us in exploring a new generation of broad nAbs as key therapeutics to tackle SARS-CoV-2 and accelerate the exploration of novel clinical antiviral reagents.