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This paper introduces a modular simulation testbed developed for decision support in logistics and urban planning within the tourism sector, specifically applied to Şanlıurfa, Turkey, as part of the GeostaloVR project. The testbed integrates tourism value chains, urban development processes, and mobility flows to facilitate scenario testing and evaluation. By incorporating real-world data, the simulation framework enables the analysis of key performance indicators for sustainable urban tourism development. This approach aims to advance the application of modeling techniques to address complex challenges in urban tourism in order to provide valuable insights for stakeholders involved in urban and logistics planning.

Conformer–rotamer sampling tool (CREST) is an open-source program for the efficient and automated exploration of molecular chemical space. Originally developed in Pracht et al. [Phys. Chem. Chem. Phys. 22, 7169 (2020)] as an automated driver for calculations at the extended tight-binding level (xTB), it offers a variety of molecular- and metadynamics simulations, geometry optimization, and molecular structure analysis capabilities. Implemented algorithms include automated procedures for conformational sampling, explicit solvation studies, the calculation of absolute molecular entropy, and the identification of molecular protonation and deprotonation sites. Calculations are set up to run concurrently, providing efficient single-node parallelization. CREST is designed to require minimal user input and comes with an implementation of the GFNn-xTB Hamiltonians and the GFN-FF force-field. Furthermore, interfaces to any quantum chemistry and force-field software can easily be created. In this article, we present recent developments in the CREST code and show a selection of applications for the most important features of the program. An important novelty is the refactored calculation backend, which provides significant speed-up for sampling of small or medium-sized drug molecules and allows for more sophisticated setups, for example, quantum mechanics/molecular mechanics and minimum energy crossing point calculations. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome coronavirus (MERSCoV) circulates in dromedary camels in the Arabian Peninsula and occasionally causes spillover infections in humans. MERS-CoV diversity is poorly understood because of the lack of sampling during the COVID-19 pandemic. We collected 558 swab samples from dromedary camels in Saudi Arabia during November 2023-January 2024. We found 39% were positive for MERS-CoV RNA by reverse transcription PCR. We sequenced 42 MERSCoVs and 7 human 229E-related coronaviruses from camel swab samples by using high-throughput sequencing. Sequences from both viruses formed monophyletic clades apical to recently available genomes. MERS-CoV sequences were most similar to B5 lineage sequences and harbored unique genetic features, including novel amino acid polymorphisms in the spike protein. Further characterization will be required to understand their effects. MERS-CoV spillover into humans poses considerable public health concerns. Our findings indicate surveillance and phenotypic studies are needed to identify and monitor MERS-CoV pandemic potential. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract. In contrast, two bat sarbecovirus S proteins drove cell entry in an ACE2-independent, trypsin-dependent fashion and several ACE2-dependent S proteins could switch to the ACE2-independent entry pathway when exposed to trypsin. Several TMPRSS2-related cellular proteases but not the insertion of a multibasic cleavage site into the S protein allowed for ACE2-independent entry in the absence of trypsin and may support viral spread in the respiratory tract. Finally, the pan-sarbecovirus antibody S2H97 enhanced cell entry driven by two S proteins and this effect was reversed by trypsin while trypsin protected entry driven by a third S protein from neutralization by S2H97. Similarly, plasma from quadruple vaccinated individuals neutralized entry driven by all S proteins studied, and availability of the ACE2-independent, trypsin-dependent pathway reduced neutralization sensitivity. In sum, our study reports a pathway for entry into human cells that is ACE2-independent, can be supported by TMPRSS2-related proteases and may be associated with antibody evasion. Author summary: Bats host a wide range of coronaviruses, including those related to SARS-CoV-1 and SARS-CoV-2 (subgenus Sarbecovirus), but their ability to infect human cells remains poorly understood. Identifying sarbecoviruses with zoonotic potential and understanding the factors controlling their entry into human cells are crucial for risk assessment and antiviral development. In this study, we examined how bat sarbecovirus spike proteins facilitate entry into human cells and identified key host factors involved. Using pseudovirus particles, we show that several bat sarbecovirus spike proteins use human and animal ACE2 receptors for entry. Additionally, we confirm that some spike proteins utilize an ACE2-independent entry pathway requiring trypsin treatment and demonstrate that this process is controlled by the spike protein receptor binding domain. Furthermore, we reveal that a subset of ACE2-using bat sarbecovirus spike proteins can switch to ACE2-independent entry following trypsin exposure and show that certain human type II transmembrane serine proteases can substitute for trypsin, enabling ACE2-independent entry. Finally, we demonstrate that repeated COVID-19 vaccination generates cross-neutralizing activity against bat sarbecoviruses, though ACE2-independent entry reduces neutralization sensitivity. [ABSTRACT FROM AUTHOR]