Ethical guidelines for deliberately infecting volunteers with COVID-19.

Global fatalities related to COVID-19 are expected to be high in 2020-2021. Developing and delivering a vaccine may be the most likely way to end the pandemic. If it were possible to shorten this development time by weeks or months, this may have a significant effect on reducing deaths. Phase II and phase III trials could take less long to conduct if they used human challenge methods-that is, deliberately infecting participants with COVID-19 following inoculation. This article analyses arguments for and against such methods and provides suggested broad guidelines for regulators, researchers and ethics committees when considering these matters. It concludes that it may be possible to maintain current ethical standards yet still permit human challenge trials in a context where delay is critical. The implications are that regulators and researchers need to work together now to design robust but short trials and streamline ethics approval processes so that they are in place when applications for trials are made.

Antimicrobial activity of ruthenium-based intercalators.

Multidrug resistance of bacterial pathogens is a major problem and there is a clear need for the development of new types of antibiotics. Here we investigated the antimicrobial activity of ruthenium(II) based DNA-intercalating complexes. These complexes were found to have no activity in vitro against the Gram-negative bacterium Escherichia coli, but the complexes were clearly active against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. In vivo activity has also been demonstrated for one of the compounds using a simple infection model, the nematode Caenorhabditis elegans. Importantly, this also showed that the compound tested was not toxic to the nematodes.

Antimicrobial activity of an iron triple helicate.

The prevalence of antibiotic resistance has resulted in the need for new approaches to be developed to combat previously easily treatable infections. Here we investigated the potential of the synthetic metallomolecules [Fe(2)L(3)](4+) and [Cu(2)(L')(2)](2+) as antibacterial agents. Both molecules have been shown to bind DNA; [Fe(2)L(3)](4+) binds in the major groove and causes DNA coiling, whilst [Cu(2)(L')(2)](2+) can act as an artificial nuclease. The work described here shows that only [Fe(2)L(3)](4+) is bactericidal for Bacillus subtilis and Escherichia coli. We demonstrate that [Fe(2)L(3)](4+) binds bacterial DNA in vivo and, strikingly, that it kills B. subtilis cells very rapidly.

Synthetic metallomolecules as agents for the control of DNA structure.

This tutorial review summarises B-DNA structure and metallomolecule binding modes and illustrates some DNA structures induced by molecules containing metallic cations. The effects of aquated metal ions, cobalt amines, ruthenium octahedral metal complexes, metallohelicates and platinum complexes such as cis-platin are discussed alongside the techniques of NMR, X-ray crystallography, gel electrophoresis, circular dichroism, linear dichroism and molecular dynamics. The review will be of interest to people interested in both DNA structure and roles of metallomolecules in biological systems.