Two-Helix Supramolecular Proteomimetic Binders Assembled via PNA-Assisted Disulfide Crosslinking.

Peptidic motifs folded in a defined conformation are able to inhibit protein-protein interactions (PPIs) covering large interfaces and as such they are biomedical molecules of interest. Mimicry of such natural structures with synthetically tractable constructs often requires complex scaffolding and extensive optimization to preserve the fidelity of binding to the target. Here, we present a novel proteomimetic strategy based on a 2-helix binding motif that is brought together by hybridization of peptide nucleic acids (PNA) and stabilized by a rationally positioned intermolecular disulfide crosslink. Using a solid phase synthesis approach (SPPS), the building blocks are easily accessible and such supramolecular peptide-PNA helical hybrids could be further coiled using precise templated chemistry. The elaboration of the structural design afforded high affinity SARS CoV-2 RBD (receptor binding domain) binders without interference with the underlying peptide sequence, creating a basis for a new architecture of supramolecular proteomimetics.

Examples of Structural Motifs in Viral Genomes and Approaches for RNA Structure Characterization.

The relationship between conserved structural motifs and their biological function in the virus replication cycle is the interest of many researchers around the world. RNA structure is closely related to RNA function. Therefore, technological progress in high-throughput approaches for RNA structure analysis and the development of new ones are very important. In this mini review, we discuss a few perspectives on the structural elements of viral genomes and some methods used for RNA structure prediction and characterization. Based on the recent literature, we describe several examples of studies concerning the viral genomes, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV). Herein, we emphasize that a better understanding of viral genome architecture allows for the discovery of the structure-function relationship, and as a result, the discovery of new potential antiviral therapeutics.

Signal hotspot mutations in SARS-CoV-2 genomes evolve as the virus spreads and actively replicates in different parts of the world.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China late in 2019. Nine months later (Sept. 23, 2020), the virus has infected > 31.6 million people around the world and caused > 971.000 (3.07 %) fatalities in 220 countries and territories. Research on the genetics of the SARS-CoV-2 genome, its mutants and their penetrance can aid future defense strategies. By analyzing sequence data deposited between December 2019 and end of May 2020, we have compared nucleotide sequences of 570 SARS-CoV-2 genomes from China, Europe, the US, and India to the sequence of the Wuhan isolate. During worldwide spreading among human populations, at least 10 distinct hotspot mutations had been selected and found in up to > 80 % of viral genomes. Many of these mutations led to amino acid exchanges in replication-relevant viral proteins. Mutations in the SARS-CoV-2 genome would also impinge upon the secondary structure of the viral RNA molecule and its repertoire of interactions with essential cellular and viral proteins. The increasing frequency of SARS-CoV-2 mutation hotspots might select for dangerous viral pathogens. Alternatively, in a 29.900 nucleotide-genome, there might be a limit to the number of mutable and selectable sites which, when exhausted, could prove disadvantageous to viral survival. The speed, at which novel SARS-CoV-2 mutants are selected and dispersed around the world, could pose problems for the development of vaccines and therapeutics.