The SARS-CoV-2 B.1.1.529 variant (Omicron) comprises 15 mutations on the receptor-binding area (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) requires fast investigation. Here, we used high-throughput yeast show screening1,2 to find out the RBD escaping mutation profiles for 247 human anti-RBD NAbs and confirmed that the NAbs could possibly be unsupervised clustered into six epitope teams (A-F), which is extremely concordant with knowledge-based structural classifications3-5. Strikingly, numerous single mutations of Omicron might impair NAbs of completely different epitope teams. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 website)6 and F (CR3022 website)7 NAbs, which frequently exhibit broad sarbecovirus neutralizing exercise, are much less affected by Omicron, however nonetheless, a subset of NAbs are escaped by G339D, N440K, and S371L. Furthermore, Omicron pseudovirus neutralization confirmed that single mutation tolerating NAbs is also escaped because of a number of synergetic mutations on their epitopes. In complete, over 85% of the examined NAbs are escaped by Omicron. Regarding NAb medication, the neutralization efficiency of LY-CoV016/LY-CoV555, REGN10933/REGN10987, AZD1061/AZD8895, and BRII-196 had been vastly decreased by Omicron, whereas VIR-7831 and DXP-604 nonetheless operate at decreased efficacy. Together, information recommend Omicron would trigger vital humoral immune evasion, whereas NAbs focusing on the sarbecovirus conserved area stay handiest. Our outcomes provide directions for creating NAb medication and vaccines in opposition to Omicron and future variants.