Lai, Guan ChunGuan ChunLaiTAI-LING CHAOLin, Shiau YuShiau YuLinKao, Han ChiehHan ChiehKaoTsai, Ya MinYa MinTsaiLu, De ChaoDe ChaoLuChiang, Yi WeiYi WeiChiangSUI-YUAN CHANGSHIH-CHUNG CHANG2022-04-142022-04-142022-04-0101663542https://scholars.lib.ntu.edu.tw/handle/123456789/604312Neutralizing antibodies (NAbs) are believed to be promising prophylactic and therapeutic treatment against the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported two mouse monoclonal antibodies 7 Eb-4G and 1Ba–3H that specifically recognized the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein without exhibiting cross-reactivity with the S proteins of SARS-CoV and MERS-CoV. The binding epitopes of 7 Eb-4G and 1Ba–3H were respectively located in the regions of residues 457–476 and 477–496 in the S protein. Only 1Ba–3H exhibited the neutralizing activity for preventing the pseudotyped lentivirus from binding to the angiotensin-converting enzyme 2 (ACE2)-transfected HEK293T cells. The competitive ELISA further showed that 1Ba–3H interfered with the binding between RBD and ACE2. Epitope mapping experiments demonstrated that a single alanine replacement at residues 480, 482, 484, 485, and 488–491 in the RBD abrogated 1Ba–3H binding. 1Ba–3H exhibited the neutralizing activity against the wild-type, Alpha, Delta, and Epsilon variants of SARS-CoV-2, but lost the neutralizing activity against Gamma variant in the plaque reduction assay. On the contrary, 1Ba–3H enhanced the cellular infection of Gamma variant in a dose-dependent manner. Our findings suggest that the antibody-dependent enhancement of infection mediated by the RBD-specific antibody for different SARS-CoV-2 variants must be considered while developing the NAb.ACE2 | Antibody-dependent enhancement | COVID-19 | Neutralizing antibody | SARS-CoV-2 | Spike receptor binding domainjournal article10.1016/j.antiviral.2022.1052902-s2.0-85126524351https://api.elsevier.com/content/abstract/scopus_id/85126524351