Next-generation sequencing (NGS) allows for analyzing a large number of viral sequences from infected patients, providing an opportunity to implement large-scale molecular surveillance of viral diseases. However, despite improvements in technology, traditional protocols for NGS of large numbers of samples are still highly cost and labor intensive. One of the possible cost-effective alternatives is combinatorial pooling. Although a number of pooling strategies for consensus sequencing of DNA samples and detection of SNPs have been proposed, these strategies cannot be applied to sequencing of highly heterogeneous viral populations.