Cross-Neutralizing Monoclonal Antibodies with Broad Activity Against Human and Bat-Derived SARS-Related Coronaviruses

Abstract

Effective therapeutics for severe cases of SARS-CoV-2 are still needed. As new variants of concern emerged an increase in hospitalizations was observed, especially in non-vaccinated individuals, immunocompromised individuals and the elderly, whereby treatment options became challenging. Several monoclonal antibodies (mAb) are being evaluated for approval due to their ability to neutralize the virus. Here, we report monoclonal antibodies targeting the Spike (S) with a strong neutralization profile against lentiviral and VSV pseudotypes displaying the Spikes of SARS-CoV-1, SARS-CoV-2 and variants of concern, in addition to two bat coronaviruses. We found several mAbs that were able to bind and neutralize a broad set of variants, with one mAb able to neutralize SARS-CoV-1, SARS-CoV-2, RaTG13 and WIV16. Their binding affinities were also characterized, and several mAbs were in the picomolar range against different variants. These results indicate that their use as a cocktail of monoclonal antibodies to treat patients infected with variants associated with severe disease and immune escape can be explored as an option. Furthermore, the cross reactivity observed by one mAb may reveal further insight into vulnerable portions of the Spike protein, which may become valuable future targets.