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The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks., Graphical abstract, Napolitano et al. discovered acriflavine (ACF), a clinically approved drug, as an effective inhibitor of SARS-CoV-2 papain-like protease (PLpro). ACF inhibits viral replication at nanomolar concentrations in vitro and ex vivo, as well as in vivo. These findings open a promising therapeutic approach against COVID-19 and other betacoronaviruses.

The popular success of commercial films depicting events of mass atrocity is the theme of this contribution. Films on the theme of the Holocaust or the Rwandan genocide, for example, demonstrate a demand amongst audiences for a cinematic experience of genocide. The author addresses the extent to which filmic representations of genocide include elements that purport to elucidate the causes, organisation and perpetration of such events of mass atrocity. Genocide films tend to harbour implicit criminologies and it is to those that attention is directed in this contribution. A reflective documentary analysis is conducted on the films Schindler’s List (Spielberg, 1993), Conspiracy (Pierson, 2001), Hotel Rwanda (George, 2004) and Sometimes in April (Peck, 2005). These films enable the exploration of representations which chronicle the experience of genocide from the perspectives of victims, perpetrators and bystanders.

Flexible silicon nitride clips are used to hold single mode optical fibres in position in grooves etched in silicon substrates to connect either subsurface or surface mounted optical components. The fabrication process for the buried fibre connector requires only one lithographic step, and a silicon substrate coated with a 3 m thick silicon nitride film. The light coupled between two single mode optic fibres buried in the same V groove has been measured as a function of the separation of the ends of the fibres. The Young's modulus and mechanical properties of silicon nitride from various sources have been measured using the clips. In another process using two lithographic steps a clipped fibre is made having the fibre core level with the silicon surface or up to 20 m above it, and the tolerances are sufficiently tight for optical system manufacture. Light coupling has been demonstrated between a semiconductor laser and a fibre. The clip technology is versatile and tolerant of lateral and angular misalignments during insertion. Fabrication and mechanical design rules for the silicon nitride clip technology are summarized, and possible applications in fibre connection, waveguide sensor and telecommunication systems are discussed.

Integrated optics will be more widely exploited when the integration of building blocks is low cost, versatile and reliable. Interconnection between active and passive components is a critical part of building such devices. We have developed a proprietary method for achieving fully passive alignment of optical fibres to other critical components using standard Si processing technologies. It is therefore stable for low cost high volume manufacture. High yields and excellent stability over a wide range of environmental conditions have been demonstrated.

This paper reviews bulk micromachining of Si, with particular reference to the microassembly and packaging of optical and electronic components. Taking as an example the use of 2.3 [.proportional]m thick silicon nitride microclips to hold an optic fibre in place in a silicon V-groove, the potential of thin film packaging is briefly assessed. The fabrication process is to: [i] deposit a controlled stress silicon nitride layer onto a blank (100) oriented silicon wafer by chemical vapour deposition (standard LPCVD but silicon rich); [ii] pattern the silicon nitride clip mask shape by optical lithography and reactive ion etching; and [iii] remove the underlying silicon to form a V-shaped groove with an anisotropic liquid etch process using the silicon nitride as a mask. From the measured deflection of a silicon nitride beam when a force is applied, the Young's modulus is 400 GPa. The beams are rugged and a clipping force of 10 N per metre of optic fibre length is achieved.This approach to applying the mechanical properties of thin films is compatible with standard thin film technology, enables precise microassembly, and has great potential to reduce manufacturing costs in a wide range of sensors and microsystems. In some applications high temperature processing must be avoided, even early on in the manufacturing process. Using low temperature processing, robust clips from silicon nitride made by plasma enhanced chemical vapour deposition (PECVD and hydrogen rich) are made, but the Young's modulus of this material is typically 40 GPa and the clipping force is correspondingly small. The paper concludes by assessing the prospects for other thin film materials in mechanical MEMS and packaging.

Microengineering technologies are being rapidly applied to make precise connections between optical components and fibres, and between fibres. Anisotropic etching of silicon enables the accurate fabrication of V-shaped grooves to locate optic fibres. Single mode fibres can be positioned using microfabricated clips 3 micron thick with a clipping force of 10 Nm/sup -1/. This demountable technology enables low cost assembly without the need for active alignment.