The coronavirus named as SARS-CoV-2 is the cause of the COVID-19 pandemic and spreading rapidly1. It is a pneumonia outbreak2 with T cell exhaustion, cytokine storm and coagulation3,4. Short motifs on proteins play important roles on protein-protein interactions5,6. We hypothetized role of molecular mimicry of small-xxx-small motifs for the spike protein of SARS-CoV-2. Here we show that a unique and evolutionary conserved motif is found only on the spike protein of SARS-CoV-2 and stimulator of interferon genes (STING) proteins. Surprisingly we could not find this motif on any other protein of any living form. We found a similar, but not identical motif mimicry for the spike and regulator of G protein signaling 12 (RGS12), C1QT4 and also for proteins of Archaea and beta-lactamase enzymes of bacteria including Mycobacterium tuberculosis. STING proteins have roles on coagulation, T cell exhaustion, cytokine release1-3 and RGS12 on inflammation7. In contrast to cGAS-STING pathway8, the motif mimicry indicated a direct interaction between spike and STING proteins suggesting the importance of STING, RGS12 and C1QT4 on the pathogenesis of COVID-19. To our surprise, the molecular mimicry showed that beta-lactamase inhbitors may be effective against SARS-CoV-2. The motif is unique, as found on Archaea and Cnidaria it is evolutionary old but a new target and mechanism for the COVID-19.