Viral infection has been one of the major health issues for human life. The real-time reverse transcription polymerase chain reaction (RT-PCR)-based detection has primarily been used for virus detection as a highly reliable procedure. However, it is a relatively long and multi-stage process. In addition, required skilled personnel and complex instrumentation presents difficulties in large scale monitoring efforts. Therefore, we report here a direct and fast detection method for CoV-2 genome as applied in the nose-throat swab samples without any further processing. The detection principle is based on fluorescein-loaded mesoporous silica nanoparticles capped by specific gene sequences probes immobilized on the surface of the nanoparticles. Upon hybridization with the target viral genome, the fluorescein molecules were released from the mesopores. Testing with synthetic oligonucleotides, the NSP12 gene-based detection resulted in a strong signal. Target detection time could be optimized to 15 min and the limit of detection was 1.4 RFU with 84% sensitivity with clinical samples (n = 43). Display omitted •A rapid biosensor for viruses.•Direct detection from nose-throat swab samples.•Detection time was 15 min.•Probe-gated silica nanoparticles were used to detect SARS-CoV-2 in clinical samples.