Light-Induced Transformation of Virus-Like Particles on TiO2.

Titanium dioxide (TiO2) shows significant potential as a self-cleaning material to inactivate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent virus transmission. This study provides insights into the impact of UV-A light on the photocatalytic inactivation of adsorbed SARS-CoV-2 virus-like particles (VLPs) on a TiO2 surface at the molecular and atomic levels. X-ray photoelectron spectroscopy, combined with density functional theory calculations, reveals that spike proteins can adsorb on TiO2 predominantly via their amine and amide functional groups in their amino acids blocks. We employ atomic force microscopy and grazing-incidence small-angle X-ray scattering (GISAXS) to investigate the molecular-scale morphological changes during the inactivation of VLPs on TiO2 under light irradiation. Notably, in situ measurements reveal photoinduced morphological changes of VLPs, resulting in increased particle diameters. These results suggest that the denaturation of structural proteins induced by UV irradiation and oxidation of the virus structure through photocatalytic reactions can take place on the TiO2 surface. The in situ GISAXS measurements under an N2 atmosphere reveal that the virus morphology remains intact under UV light. This provides evidence that the presence of both oxygen and UV light is necessary to initiate photocatalytic reactions on the surface and subsequently inactivate the adsorbed viruses. The chemical insights into the virus inactivation process obtained in this study contribute significantly to the development of solid materials for the inactivation of enveloped viruses.

SARS-CoV-2 and Epstein-Barr Virus-like Particles Associate and Fuse with Extracellular Vesicles in Virus Neutralization Tests.

The successful development of effective viral vaccines depends on well-known correlates of protection, high immunogenicity, acceptable safety criteria, low reactogenicity, and well-designed immune monitoring and serology. Virus-neutralizing antibodies are often a good correlate of protective immunity, and their serum concentration is a key parameter during the pre-clinical and clinical testing of vaccine candidates. Viruses are inherently infectious and potentially harmful, but we and others developed replication-defective SARS-CoV-2 virus-like-particles (VLPs) as surrogates for infection to quantitate neutralizing antibodies with appropriate target cells using a split enzyme-based approach. Here, we show that SARS-CoV-2 and Epstein-Barr virus (EBV)-derived VLPs associate and fuse with extracellular vesicles in a highly specific manner, mediated by the respective viral fusion proteins and their corresponding host receptors. We highlight the capacity of virus-neutralizing antibodies to interfere with this interaction and demonstrate a potent application using this technology. To overcome the common limitations of most virus neutralization tests, we developed a quick in vitro diagnostic assay based on the fusion of SARS-CoV-2 VLPs with susceptible vesicles to quantitate neutralizing antibodies without the need for infectious viruses or living cells. We validated this method by testing a set of COVID-19 patient serum samples, correlated the results with those of a conventional test, and found good sensitivity and specificity. Furthermore, we demonstrate that this serological assay can be adapted to a human herpesvirus, EBV, and possibly other enveloped viruses.

Quantitation of SARS-CoV-2 neutralizing antibodies with a virus-free, authentic test.

Neutralizing antibodies (NAbs), and their concentration in sera of convalescents and vaccinees are a correlate of protection from COVID-19. The antibody concentrations in clinical samples that neutralize SARS-CoV-2 are difficult and very cumbersome to assess with conventional virus neutralization tests (cVNTs), which require work with the infectious virus and biosafety level 3 containment precautions. Alternative virus neutralization tests currently in use are mostly surrogate tests based on direct or competitive enzyme immunoassays or use viral vectors with the spike protein as the single structural component of SARS-CoV-2. To overcome these obstacles, we developed a virus-free, safe and very fast (4.5 h) in vitro diagnostic test based on engineered yet authentic SARS-CoV-2 virus-like-particles (VLPs). They share all features of the original SARS-CoV-2 but lack the viral RNA genome and thus are non-infectious. NAbs induced by infection or vaccination, but also potentially neutralizing monoclonal antibodies can be reliably quantified and assessed with ease and within hours with our test, because they interfere and block the ACE2-mediated uptake of VLPs by recipient cells. Results from the VLP neutralization test (VLPNT) showed excellent specificity and sensitivity and correlated very well with a cVNT using fully infectious SARS-CoV-2. The results also demonstrated the reduced neutralizing capacity of COVID-19 vaccinee sera against variants of concern of SARS-CoV-2 including omicron B.1.1.529, BA.1.

The practical other: teleology and its development.

We argue for teleology as a description of the way in which we ordinarily understand others' intentional actions. Teleology starts from the close resemblance between the reasoning involved in understanding others' actions and one's own practical reasoning involved in deciding what to do. We carve out teleology's distinctive features more sharply by comparing it to its three main competitors: theory theory, simulation theory, and rationality theory. The plausibility of teleology as our way of understanding others is underlined by developmental data in its favour.

Pro-social cognition: helping, practical reasons, and 'theory of mind'.

There is converging evidence that over the course of the second year children become good at various fairly sophisticated forms of pro-social activities, such as helping, informing and comforting. Not only are toddlers able to do these things, they appear to do them routinely and almost reliably. A striking feature of these interventions, emphasized in the recent literature, is that they show precocious abilities in two different domains: they reflect complex 'theory of mind' abilities as well as 'altruistic motivation'. Our aim in this paper is to present a theoretical hypothesis that bears on both kinds of developments. The suggestion is that children's 'instrumental helping' reflects their budding understanding of practical reasons (in the standard sense of 'considerations that count in favour of' someone's acting in a certain way). We can put the basic idea in the familiar terminology of common coding: toddlers conceive of the goals of others' actions in the same format as the goals of their own actions: in terms of features of their situation that provide us with reasons to act.

Competition as rational action: why young children cannot appreciate competitive games.

Understanding rational actions requires perspective taking both with respect to means and with respect to objectives. This study addresses the question of whether the two kinds of perspective taking develop simultaneously or in sequence. It is argued that evidence from competitive behavior is best suited for settling this issue. A total of 71 kindergarten children between 3 and 5 years of age participated in a competitive game of dice and were tested on two traditional false belief stories as well as on several control tasks (verbal intelligence, inhibitory control, and working memory). The frequency of competitive poaching moves in the game correlated with correct predictions of mistaken actions in the false belief task. Hierarchical linear regression after controlling for age and control variables showed that false belief understanding significantly predicted the amount of poaching moves. The results speak for an interrelated development of the capacity for "instrumental" and "telic" perspective taking. They are discussed in the light of teleology as opposed to theory use and simulation.

From infants' to children's appreciation of belief.

Evidence is accumulating that infants are sensitive to people's false beliefs, whereas children pass the standard false belief test at around 4 years of age. Debate currently centres on the nature of early and late understanding. We defend the view that early sensitivity to false beliefs shown in 'online tasks' (where engagement with ongoing events reflects an expectation of what will happen without a judgement that it will happen) reflects implicit/unconscious social knowledge of lawful regularities. The traditional false belief task requires explicit consideration of the agent's subjective perspective on his reasons for action. This requires an intentional switch of perspectives not possible before 4 years of age as evidenced by correlations between the false belief task and many different perspective-taking tasks.