Jiazheng Guo

Three pandemics caused by human Betacoronavirus had broken out in the past two decades. Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) was one of the novel epidemic strains which caused the third pandemic, coronavirus disease 2019 (COVID‐19), a global public health crisis. So far, more than millions of people have been infected. Considering the public health and economic impact of Betacoronavirus pandemic, drugs with broad‐spectrum activity against these coronaviruses are urgently needed. In this study, two monoclonal antibodies targeting SARS‐CoV‐2 spike protein receptor‐binding domain (RBD) with good neutralizing activity were used to construct a novel immunoglobulin‐like bispecific antibody BI31. The neutralizing effect of BI31 against the pseudovirus and the authentic virus is better than that of its parent antibodies alone and in combination. What surprised us most was that the newly constructed bispecific antibody also had the neutralizing activity against SARS‐CoV and Middle East respiratory syndrome coronavirus (MERS‐CoV) that the parent antibodies did not have. These suggested that the BI31 can not only be developed as a therapeutic drug against COVID‐19 but it could also become a broad‐spectrum therapeutic antibody against Betacoronavirus.

The emerging coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is the causative agent of coronavirus disease 2019 (COVID‐19), which has become a severe threat to global public health and local economies. In this study, several single‐chain antibody fragments that bind to the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike (S) protein were identified and used to construct human‐mouse chimeric antibodies and humanized antibodies. These antibodies exhibited strong binding to RBD and neutralization activity towards a SARS‐CoV‐2 pseudovirus. Moreover, these antibodies recognize different RBD epitopes and exhibit synergistic neutralizing activity. These provide candidate to combination use or bispecific antibody to potential clinical therapy for COVID‐19.