Targeting protein-protein interaction interfaces in COVID-19 drug discovery.

To date, the COVID-19 pandemic has claimed over 1 million human lives, infected another 50 million individuals and wreaked havoc on the global economy. The crisis has spurred the ongoing development of drugs targeting its etiological agent, the SARS-CoV-2. Targeting relevant protein-protein interaction interfaces (PPIIs) is a viable paradigm for the design of antiviral drugs and enriches the targetable chemical space by providing alternative targets for drug discovery.

Unraveling cardiolipin-induced conformational change of cytochrome c through H/D exchange mass spectrometry and quartz crystal microbalance.

Cardiolipin (CL), a crucial component in inner mitochondrial membranes, interacts with cytochrome c (cyt c) to form a peroxidase complex for the catalysis of CL oxidation. Such interaction is pivotal to the mitochondrial regulation of apoptosis and is affected by the redox state of cyt c. In the present study, the redox-dependent interaction of cyt c with CL was investigated through amide hydrogen/deuterium exchange coupled with mass spectrometry (HDXMS) and quartz crystal microbalance with dissipation monitoring (QCM-D).

Polymerase-assisted fluorescence resonance energy transfer (FRET) assay for simultaneous detection of binary viral sequences.

The analysis of a specific sequence of nucleic acids enables identification of pathogens and the diagnosis of human genetic disorders. This emphasises the need to develop methods of detecting nucleic acids, particularly in a multiplex format, that yield a decisive conclusion for clinical interpretation. Herein, we introduce a polymerase-assisted fluorescence resonance energy transfer (FRET) assay to simultaneously analyse binary viral genes that are characteristic of hemagglutinin and neuraminidase in influenza A virus.

A mutation-resistant deoxyribozyme OR gate for highly selective detection of viral nucleic acids.

Highly selective probes hybridize only to fully complementary DNA or RNA sequences and, therefore, often fail to recognize mutated viral genomes. Here we designed a probe that possesses two seemingly incompatible properties: it tolerates some point mutations in genome, while it remains selective towards others. An OR deoxyribozyme logic gate was designed to fluorescently report the sequences of enterovirus 71 (EV71) covering ∼90% of all known EV71 strains.

Biosensors with built-in biomolecular logic gates for practical applications.

Molecular logic gates, designs constructed with biological and chemical molecules, have emerged as an alternative computing approach to silicon-based logic operations. These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control. In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions.