© 2022 Elsevier B.V.A label-free electrochemical biosensing approach as an appropriate analysis technique for SARS-CoV-2 spike protein (SARS-CoV-2 S-protein) was investigated to facilitate the diagnosis of coronavirus in real samples. It is crucial to construct diagnostic features that can rapidly identify infected individuals to limit the spread of the virus and assign treatment choices. Therefore, a novel and selective method using SiO2@UiO-66 and a label-free electrochemical immunoassay for rapidly detecting spike protein. The development of innovative approaches for direct viral detection employing simplified and ideally reagent-free assays is a pressing and difficult topic. The absence of speedy and effective ways to diagnose viral diseases especially SARS-CoV-2 on demand has worsened the issue of combating the COVID-19 pandemic. The developed electrode illustrated a wide dynamic range of 100.0 fg mL−1 to 10.0 ng mL−1 with low limit detection. Therefore, the as-fabricated electrochemical SARS-CoV-2 S-protein sensor suggests an appropriate perspective in the point-of-care system, within 5.0 min, in nasal samples with satisfactory recovery.