17 years after the SARS-CoV epidemic, the world is facing the COVID-19 pandemic.COVID-19 is caused by a coronavirus named SARS-CoV-2. Given the most optimistic projections estimating that it will take more than a year to develop a vaccine, our best short term strategy may lie in identifying virus-specific targets for small molecule interventions. All coronaviruses utilize a molecular mechanism called -1 PRF to control the relative expression of their proteins. Prior analyses of SARS-CoV revealed that it utilizes a structurally unique three-stemmed mRNA pseudoknot to stimulate high rates of -1 PRF, that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity negatively impacts virus replication, suggesting that this molecular mechanism may be therapeutically targeted. Here we present a comparative analysis of the original SARS-CoV and SARS-CoV-2 frameshift signals. Structural analyses reveal that the core -1 PRF signal, composed of the U UUA AAC slippery site and three-stemmed mRNA pseudoknot is highly conserved. In contrast, the upstream attenuator hairpin is less well conserved. Functional assays revealed that both elements promote similar rates of -1 PRF and that silent coding mutations in the slippery site strongly ablate -1 PRF activity. We suggest that molecules that were previously identified as inhibiting SARS-CoV mediated -1 PRF may serve as lead compounds to counter the current pandemic.

Systemic lupus erythematosus (SLE) is a prototype systemic, autoimmune inflammatory disease that can involve virtually any organ or tissue type. The disease has a strong familial tendency but, like most human illness, has a complex pattern of inheritance that is consistent with multiple susceptibility genes as well as environmental risk factors. Association studies have been performed, especially for the major histocompatibility complex on chromosome 6 and for various complement components. Several large familial studies have begun to report results for genetic linkage. Linkage has been established for many genetic intervals. SLE is a complex clinical illness, and investigation of the genetics of the illness based on clinical manifestations revealed linkages not found without consideration of the phenotype of the disease.