A review.Severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a pandemic with severe economic losses.Bruel et al. compared the neutralizing activity of therapeutic mAbs against the Omicron subvariants BA.1 and BA.2 and analyzed the serum-neutralizing activity of immunocompromised people after treatment with anti-COVID-19 mAb cocktails.Although anti-RBD mAbs may neutralize the original strain of SARS-CoV-2, many show reduced neutralizing activity against SARS-CoV-2 VOCs, particularly the Omicron variant.In conclusion, the results presented by Bruel et al. demonstrate that SARS-CoV-2 RBD-targeting therapeutic mAbs or mAb cocktails have different abilities to neutralize Omicron, particularly the BA.1 and BA.2 subvariants.In addition to mAbs targeting the RBD, mAbs targeting other regions of the SARS-CoV-2 S protein (particularly the conserved S2 subunit) have the potential to neutralize multiple variants, including Omicron, and these mAbs may be developed as alternative therapeutics.Overall, anti-SARS-CoV-2 mAbs can be developed to target onserved neutralizing epitopes of the S protein. In particular, cocktails comprising mAbs targeting conserved and nonoverlapping epitopes on the RBD, S2, and/or NTD regions are expected to have synergistic effects and show broad and improved neutralizing activity for preventing and treating infection by SARS-CoV-2 (including Omicron and its subvariants, future variants) and other coronaviruses with pandemic potential.Hese studies suggest that neutralizing mAbs that recognize highly conserved epitopes, particularly those outside of the RBD RBM region, may retain potent binding and neutralizing activity against VOCs, including the Omicron variant, and thus are unlikely to be affected by the most common RBD mutations.
