Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies

The urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications.

Automated summary

Researchers compared experimentally verified SARS-CoV-2 neutralizing antibodies with commercial therapeutic monoclonal antibodies and identified three potential therapeutic antibodies targeting CTLA4 and IL17A for combating severe SARS-CoV-2 infection. These candidate antibodies have dual activities of viral neutralization and immunosuppression, and could also be utilized in diagnostic test kits for SARS-CoV-2 infection. The in silico workflow to screen and analyze antibodies for repurposing is believed to have broad applications.