Type VI CRISPR-Cas systems have been repurposed for various applications such as gene knock-down, viral interference, and molecular diagnostics. However, the identification and characterization of thermophilic orthologues will expand and unlock the potential of diverse biotechnological applications. In this work, we identified and characterized a novel, thermostable orthologue of the Cas13a family, from the thermophilic organism Thermoclostridium caenicola (TccCas13a). We show that TccCas13a has a close phylogenetic relation to HheCas13a and shares several properties such as thermostability and inability .

Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found increased interaction of GSK3A kinase simultaneously with hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. Here, we provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.

MesoCraft is a new 3D modeling tool implementing visual programming approach. It provides the user with the capabilities of loading, rendering and manipulating several modalities (protein data, volumetric data, meshes) and overlaying them inside one rendering view. The modeling algorithm is based on statistical and rule based modeling approaches that are rapid to author, fast to construct, and easy to revise. Biological information can be incorporated by interactively defining the rules that spatially characterize the biological entity, such as mutual interactions among macromolecules, and their distances and orientations relative to other structures. These rules are defined through an intuitive 3D interactive visualization as a visual programming feedback loop.