Infections from novel viral species and strains present a serious and recurring threat to global public health. Responding to these threats critically depends on the ability to identify and develop tests for the viral agent, which is a significant challenge given the diverse and rapidly-evolving sequence space of human viruses. The problem is further compounded by novel infections acquired from animal viruses, which may have little sequence similarity to any known human-infective species. In theory, next-generation sequencing (NGS) approaches can detect completely novel viral agents. However, their application is limited by contamination from host reads, requiring significant sequencing depth to obtain full coverage over the viral template. Here, we describe the Twist Comprehensive Viral Research Panel, a hybridization-based target enrichment solution capable of detecting highly divergent viral strains. Our results highlight the Twist Comprehensive Viral Research Panel as a versatile solution for novel virus discovery and surveillance.