LAUSR

As the world struggles with the ongoing COVID-19 pandemic, unprecedented obstacles have continuously been traversed as new SARS-CoV-2 variants continually emerge. Infectious disease outbreaks are unavoidable, but the knowledge gained from the successes and failures will help create a robust health management system to deal with such pandemics. Previously, scientists required years to develop diagnostics, therapeutics, or vaccines; however, we have seen that, with the rapid deployment of high-throughput technologies and unprecedented scientific collaboration worldwide, breakthrough discoveries can be accelerated and insights broadened. Computational protein design (CPD) is a game-changing new technology that has provided alternative therapeutic strategies for pandemic management. In addition to the development of peptide-based inhibitors, miniprotein binders, decoys, biosensors, nanobodies, and monoclonal antibodies, CPD has also been used to redesign native SARS-CoV-2 proteins and human ACE2 receptors. We discuss how novel CPD strategies have been exploited to develop rationally designed and robust COVID-19 treatment strategies.