The continuous emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants means there is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibody (mAb) that binds to the conserved S2 subunit of the SARS-CoV-2 spike (S) protein alone, or in combination with mAb that binds to the receptor-binding domain (RBD) of S protein, might be effective in eliciting protection from infection by a variety of SARS-CoV-2 variants. Using high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors, we identified a high-affinity S2-specific mAb-39, that could inhibit original SARS-CoV-2 strain, Omicron BA.1, BA.2.86, BA.4, BA.5, and EG.5.1 S protein-mediated membrane fusion, leading to the neutralization of these pseudoviral infections. Moreover, mAb-39 could also improve the neutralizing activity of anti-RBD antibody against the highly neutralization-resistant Omicron variants. Molecular docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2 (HR2) motif of the S2 subunit. Collectively, these findings demonstrate that targeting the conserved upstream region of the HR2 motif (e.g., using mAbs) provides a novel strategy for preventing the infection of SARS-CoV-2 and its variants.

The tumor microenvironment is a complex environment comprising tumor cells, non-tumor cells, and other critical non-cellular components. Some studies about tumor microenvironment have recently achieved remarkable progress in tumor treatment. As a substantial part of post-translational protein modification, ubiquitination is a crucial player in maintaining protein stability in cell signaling, cell growth, and a series of cellular life activities, which are also essential for regulating tumor cells or other non-tumor cells in the tumor microenvironment. This review focuses on the role and function of ubiquitination and deubiquitination modification in the tumor microenvironment while discussing the prospect of developing inhibitors targeting ubiquity-related enzymes, thereby providing ideas for future research in cancer therapy.