The lack of long-term stability for LA-EG11-Tz-TFP means it has to be prepared fresh each time before lectin conjugation, making its use inconvenient. Therefore, we prepared the more stable LA-EG11-TFP linker for protein labeling and G13 conjugation. We prepared G13-CRDs with two CRD valencies, G13-CRD100 and G13-CRD115. Their inhibition of Vero cell entry driven by the S proteins of four SARS-CoV-2 variants (i.e. Wuhan wild-type Hu-1, B.1, Delta and Omicron BA.1) was investigated (Fig. ). The dosedependent inhibition data were fitted by the model above and yielded comparable low nM EC50 values and n = 1 for G13-CRD115 against all four S proteins tested (Fig. , Table ). Interestingly, G13-CRD115 showed consistently higher potencies (~3-4 fold) than G13-CRD100 (also with n = 1) against each S protein (Table , SI Fig. .3) driven infections, suggesting that a higher CRD valency (larger Dh) is beneficial for improving antiviral potency. In contrast, clinically approved Covid-19 neutralizing Abs or sera from recovered Covid-19 patients or double vaccinated individuals were found to be either ineffective or showed greatly reduced potency against the Omicron variants (both pseudo-typed and authentic viruses). This result demonstrates a great potential of our G13-CRD based PNL as a new class of anti-SARS-CoV-2 agent. Given that the S protein glycosylation sites are conserved