Positive controls provide quality control measures for a wide range of applications from diagnostic assay development to day-to-day testing including the verification and validation of diagnostic tests of both next generation sequencing (NGS) and reverse transcription polymerase chain reaction (RT-PCR) assays. Synthetic viral controls are a powerful alternative to “live virus” controls which are viral nucleic acids extracted from either an infected patient or from live virus propagated in cell culture. Synthetic controls created through gene synthesis broaden access across diverse strains while mitigating safety and security concerns.