Lytic bacteriophage (phage) are natural viral predators of bacteria that target and kill their host(s) following infection, and therefore are of interest for a range of applications including as alternatives for antibiotic therapy, pathogen destruction during food processing, and environmental decontamination in medical and other settings. However, the process to screen phage that specifically target the microbial host of interest can be involved, sometimes requiring screening materials from unconventional sources against dangerous pathogens. Despite the historical definition of a phage as targeting only a single, highly specific bacterial species or even sub-strain, a few cases of “polyvalent” phage that target multiple closely related species, linked at the genus level, have been reported in the literature. The potential value of identifying polyvalent phage is multi-fold, including advancing towards understanding the potential for identifying “broad-spectrum” phage which have lytic activity towards many microbes, allowing for more targeted within-genus screening using lower-threat simulant hosts, and supporting the fundamental understanding of structure-function relationships between phage and their host(s). Bacillus anthracis is a biothreat microbe for which there is interest in developing phage-based decontamination strategies, however working with the dangerous pathogen requires a significant training and laboratory infrastructure investment. Therefore, mitigating approaches include developing computational screening methods, using safer simulant organisms, and assessing the applicability of the near-neighbor polyvalent phage approach for this microbe. In this work, we assess a series of phage reported in the literature or through unpublished communication to act against at least one of the below microbes to assess their lytic activity against multiple other B. anthracis near-neighbor simulants, including Bacillus subtilis, Bacillus thuringiensis, and Bacillus cereus, among others. We seek to understand the structure-function relationship between the phage activity and the genetic and structural composition of the microbe using both computational and benchtop methods. Initial results from the screens will be presented and computational analytics issues will be discussed.