Utilizing peptide-anchored DNA templates for novel programmable nanoparticle assemblies in biological macromolecules: A review.

Biological macromolecules such as proteins and DNA are known to self-assemble into various structural moieties with distinct functions. While nucleic acids are the structural building blocks, peptides exemplify diversity as tailorable biochemical units. Thus, combining the scaffold properties of the biomacromolecule DNA and the functionality of peptides could evolve into a powerful method to obtain tailorable nano assemblies. In this review, we discuss the assembly of non-DNA-coated colloidal NPs on DNA/peptide templates using functional anchors. We begin with strategies for directly attaching metallic NPs to DNA templates to ascertain the functional role of DNA as a scaffold. Followed by methods to assemble peptides onto DNA templates to emphasize the functional versatility of biologically abundant DNA-binding peptides. Next, we focus on studies corroborating peptide self-assembling into macromolecular templates onto which NPs can attach to emphasize the properties of NP-binding peptides. Finally, we discuss the assembly of NPs on a DNA template with a focus on the bifunctional DNA-binding peptides with NP-binding affinity (peptide anchors). This review aims to highlight the immense potential of combining the functional power of DNA scaffolds and tailorable functionalities of peptides for NP assembly and the need to utilize them effectively to obtain tailorable hierarchical NP assemblies.

Structural understanding of SARS-CoV-2 virus entry to host cells.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants of the virus have further exacerbated COVID-19 mortality and infection rates, emphasizing the urgent need for effective preventive strategies. Understanding the viral infection mechanism is crucial for developing therapeutics and vaccines. The entry of SARS-CoV-2 into host cells is a key step in the infection pathway and has been targeted for drug development. Despite numerous reviews of COVID-19 and the virus, there is a lack of comprehensive reviews focusing on the structural aspects of viral entry. In this review, we analyze structural changes in Spike proteins during the entry process, dividing the entry process into prebinding, receptor binding, proteolytic cleavage, and membrane fusion steps. By understanding the atomic-scale details of viral entry, we can better target the entry step for intervention strategies. We also examine the impacts of mutations in Spike proteins, including the Omicron variant, on viral entry. Structural information provides insights into the effects of mutations and can guide the development of therapeutics and vaccines. Finally, we discuss available structure-based approaches for the development of therapeutics and vaccines. Overall, this review provides a detailed analysis of the structural aspects of SARS-CoV-2 viral entry, highlighting its significance in the development of therapeutics and vaccines against COVID-19. Therefore, our review emphasizes the importance of structural information in combating SARS-CoV-2 infection.

Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression.

The G-quadruplex (G4) formed in single-stranded DNAs or RNAs plays a key role in diverse biological processes and is considered as a potential antiviral target. In the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 25 putative G4-forming sequences are predicted; however, the effects of G4-binding ligands on SARS-CoV-2 replication have not been studied in the context of viral infection. In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication and whether their antiviral activity involved stabilization of viral RNA G4s and suppression of viral gene expression. We found that pyridostatin (PDS) suppressed viral gene expression and genome replication as effectively as the RNA polymerase inhibitor remdesivir. Biophysical analyses revealed that the 25 predicted G4s in the SARS-CoV-2 genome formed a parallel G4 structure. In particular, G4-644 and G4-3467 located in the 5' region of ORF1a, formed a G4 structure that could be effectively stabilized by PDS. We also showed that PDS significantly suppressed translation of the reporter genes containing these G4s. Taken together, our results demonstrate that stabilization of RNA G4s by PDS in the SARS-CoV-2 genome inhibits viral infection via translational suppression, highlighting the therapeutic potential of G4-ligands in SARS-CoV-2 infection.

Engineered Whole-Cell-Based Biosensors: Sensing Environmental Heavy Metal Pollutants in Water-a Review.

The frequent exposure and accumulation of heavy metals in organisms cause serious health issues affecting a range of organs such as the brain, liver, and reproductive organs in adults, infants, and children. Several parts of the world have high levels of heavy metals affecting millions of people, costing millions of dollars for improving the potability of water and medical treatment of the affected. Hence, water quality assessment is required to monitor the degree of heavy metal contamination in potable water. In nature, organisms respond to various environmental pollutants such as heavy metals, allowing their survival in a diverse environmental niche. With the advent of recombinant DNA technology, it is now possible to manipulate these natural bioreporters into controlled systems which either turn on or off gene expression or activity of enzymes in the presence of specific heavy metals (compound-specific biosensors) otherwise termed as whole-cell biosensors (WCBs). WCBs provide an upper hand compared to other immunosensors, enzyme-based sensors, and DNA-based sensors since microbes can be relatively easily manipulated, scaled up with relative ease, and can detect only the bioavailable heavy metals. In this review, we summarize the current knowledge of the various mechanisms of toxicity elicited by various heavy metals, thence emphasizing the need to develop heavy metal sensing platforms. Following this, the biosensor-based platforms including WCBs for detecting heavy metals developed thus far have been briefly elaborated upon, emphasizing the challenges and solutions associated with WCBs.