The flavivirus Zika virus (ZIKV) has extensive human health impact yet lacks vaccines and antiviral treatments in part due to gaps in understanding of the its infectious cycle. To gain further insight into the infectious cycle without complete ablation of host or viral proteins we designed alpaca derived variable-heavy-chain antibody fragments (VHHs) against ZIKV. VHHs are encoded on a single gene, can be expressed in mammalian cells, and bind cognates in cytoplasm.