The overarching goal of the Prometheus CETR is to discover and develop human antibody-based prophylactics and therapeutics against two major groups of Category A priority viruses that cause severe zoonotic disease—the nairovirus Crimean-Congo hemorrhagic fever virus (CCHFV), and the hantaviruses Andes virus (ANDV), Sin Nombre virus (SNV), and Puumula virus (PUUV). CCHFV, ANDV, and SNV are Category A agents that pose the highest risk to national security and public health. In their latest annual review, the World Health Organization designated CCHF as a Blueprint Priority Disease with the greatest potential to cause a public health emergency. There are no approved vaccines or treatments for any of these agents. The Prometheus CETR, an interwoven collaboration among seven partners from academia, government, and industry organized into two projects and three cores, will accomplish two Grand Goals that are each aimed at delivering a therapeutic product against our target viral pathogens. We will develop and deliver: (1) an antibody-based therapeutic with broad efficacy against CCHFV; and (2) an antibody-based therapeutic with broad efficacy against the hantaviruses ANDV and SNV.