A newly synthesized zinc (II) oxide nanoparticle (ZnO-NPs) has been used as a disinfectant Nano-spray for the emerging corona virus (SARS-CoV-2). The synthesized obtained nanomaterial of (ZnO) was fully chemically characterized by using different spectroscopic analysis (FT-IR, UV and XRD) and surface analysis techniques. ZnO-Nps surface morphology and chemical purity has been investigated by transmission electron microscope (TEM), high resolution transmission electron microscope (HR-TEM), scanning electron microscopy (SEM) as well as energy dispersive X-ray analysis (EDX), Additionally Zeta potential and Zeta size distribution were measured and evaluated to confirm its nano-range scale. The synthesized Zno-NPs have been tested using 10% DMSO and ddH2O for estimation of antiviral activity against (SARS-CoV-2) by using cytotoxicity assay (CC50) and inhibitory concentration (IC50). The results revealed that (Zno-NPs) has high anti-SARS-CoV-2 activity at cytotoxic concentrations in vitro with non-significant selectivity index (CC50/IC50 ≤ 1). The current study results demonstrated the (ZnO-NPs) has potent antiviral activity at low concentration (IC50 = 526 ng/mL) but with some cytotoxic effect to the cell host by (CC50 = 292.2 ng/mL). We recommend using of (ZnO-NPs) as potent disinfectant against (SARS-Cov-2), but there are slight side effects on the cellular host, so we recommend more prospective studies on complexation of other compounds with (ZnO-NPs) in different concentrations to reduce its cellular toxicity and elevate its antiviral activity against SARS-CoV-2 activities.