Monoclonal antibodies capable of binding SARS‐CoV‐2 spike protein receptor‐binding motif specifically prevent GM‐CSF induction

A severe acute respiratory syndrome (SARS)‐like coronavirus 2 (SARS‐CoV‐2) has recently caused a pandemic COVID‐19 disease that infected approximately 94 million and killed more than 2,000,000 people worldwide. Like the SARS‐CoV, SARS‐CoV‐2 also employs a receptor‐binding motif (RBM) of its envelope spike protein for binding the host angiotensin‐converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS‐CoV‐2, such as the spike protein, in order to boost protective antibodies that can inhibit virus‐ACE2 interaction to prevent viral entry. It was previously unknown how spike protein‐targeting antibodies would affect innate inflammatory responses to SARS‐CoV‐2 infections. Here we generated a highly purified recombinant protein corresponding to the RBM of SARS‐CoV‐2, and used it to screen for cross‐reactive monoclonal antibodies (mAbs). We found two RBM‐binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM‐induced GM‐CSF secretion in both human peripheral blood mononuclear cells and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS‐CoV‐2‐elicited “cytokine storm,” and revealed a potentially anti‐inflammatory and protective mechanism for SARS‐CoV‐2 spike‐based vaccines.