ABSTRACT
It is commonly considered that protein-protein interactions are extremely difficult to target using small molecules. Our group uses a chemical biology approach to study the allosteric, regulatory, mechanisms of protein kinases involved in growth factor signaling downstream of PI3-kinase. Over the years we have described small molecules that target a regulatory site in AGC kinases called "PIF-Pocket", and allosterically affect the active site, ATP-binding site. We also have shown that molecules that bind to the active site of protein kinases can stimulate or inhibit protein-protein interactions at the PIF-pocket regulatory site, by a mechanism that we have termed "reverse allostery". The reverse allosteric effects are widely produced by protein kinases inhibitors that target the ATP-binding site, although the phenomenon has been almost completely unperceived by pharmaceutical industries. The presence of a reverse allosteric effect is also the cause of the paradoxical effects on the protein kinases signal transduction detected for certain inhibitors. Thus, using the knowledge of the molecular mechanism involved in the bidirectional allostery, it becomes possible to exploit it to break protein-protein interactions between protein kinases in their protein complexes (Trends Biochem Sci 45(1):27-41, 2020). We will summarize our detailed research on the protein kinase PDK1 as a model of allosteric protein and will analyze the results in the context of the modern models of allostery, "conformational selection" and "population shift". We suggest that the principles of allostery should be used to rationalize new approaches to push forward the discovery of novel drugs that break proteinprotein interactions. In line with the allosteric mechanism to disrupt protein kinase interactions, we also hypothesized that such a mechanism could also be used to break the interactions between other proteins, for example, between the angiotensin converting enzyme II (ACE2) and SARS-CoV-2 spike protein, which could be used as treatment against coronavirus infection (ChemMedChem. 15(18):1682-1690, 2020). Current studies confirm that compounds with allosteric mechanism can indeed disrupt the interaction between ACE2 and Spike. Enzymology.
ABSTRACT
Tourism shows to be one of the most affected activities by the novel coronavirus SARS-CoV-2 (responsible for COVID-19) outbreak. This situation is not only because of the cancelled flights but also of the fear of being infected with the virus. In this regard, a study was carried out intending to define and analyse the consequences of SARS-CoV-2 over the tourism intentions of Azores residents in 2020 by studying their perceptions. Throughout the research, it was possible to verify that the Azores Archipelago residents' tourism intentions were considerably modified due to SARS-CoV-2, with approximately 70% of the Azores Region residents saying that they will be spending their 2020 vacations in the region. Moreover, this article also provides insights into the enhancement of tourism safety models in regional tourism activities and consequently, in regional sustainable development and growth.
ABSTRACT
Background. Introduction: Health care personnel (HCP) are at increased risk for SARS-CoV-2 exposure. However, the exposure sources among HCP are poorly understood. Methods. Design(s): We conducted active surveillance for all employed HCP newly diagnosed with COVID-19 between March 2020 and February 2022. We inquired about their sources of exposure using a standardized health department checklist and CDC guidance for managing healthcare personnel with SARS-CoV-2 infection or exposure. Results. Among all 8,766 HCP, 2,220 (25.3%) tested positive. Among positive cases, 749 (33.7%), 651 (29.3%), and 221 (10%) were among ancillary services HCP, RNs, and allied HCP, respectively (Table 1). The majority of the sources of exposures were unknown (57.8%), followed by household (26.2%), community (10.5%), and health care (5.5%), respectively. The incidence of COVID-19 increased with level of patient contact regardless of source of exposure. The majority of the cases, N=1054 (47.5%), occurred among HCP who were not up-to-date on COVID-19 vaccines and had unknown exposure, and vaccination status varied by source of exposure (Table 2). HCP COVID-19 cases mirrored transmission in the community (Figure). Conclusion. The majority of HCP cases had no known exposure to SARS-CoV-2 and were not up-to-date on COVID-19 vaccines highlighting the importance of vaccination as the single most effective mean to COVID-19 prevention among HCP.
ABSTRACT
Highly infectious viral diseases are a serious threat to mankind as they can spread rapidly among the community, possibly even leading to the loss of many lives. Early diagnosis of a viral disease not only increases the chance of quick recovery, but also helps prevent the spread of infections. There is thus an urgent need for accurate, ultrasensitive, rapid, and affordable diagnostic techniques to test large volumes of the population to track and thereby control the spread of viral diseases, as evidenced during the COVID-19 and other viral pandemics. This review paper critically and comprehensively reviews various emerging nanophotonic biosensor mechanisms and biosensor technologies for virus detection, with a particular focus on detection of the SARS-CoV-2 (COVID-19) virus. The photonic biosensing mechanisms and technologies that we have focused on include: (a) plasmonic field enhancement via localized surface plasmon resonances, (b) surface enhanced Raman scattering, (c) nano-Fourier transform infrared (nano-FTIR) near-field spectroscopy, (d) fiber Bragg gratings, and (e) microresonators (whispering gallery modes), with a particular emphasis on the emerging impact of nanomaterials and two-dimensional materials in these photonic sensing technologies. This review also discusses several quantitative issues related to optical sensing with these biosensing and transduction techniques, notably quantitative factors that affect the limit of detection (LoD), sensitivity, specificity, and response times of the above optical biosensing diagnostic technologies for virus detection. We also review and analyze future prospects of cost-effective, lab-on-a-chip virus sensing solutions that promise ultrahigh sensitivities, rapid detection speeds, and mass manufacturability.
ABSTRACT
The aim of this study is to investigate the financial failure risk levels of the restaurant chains with the highest brand value and to reveal the impact of the Covid-19 epidemic on the financial failure risk. For this purpose, the risks of financial failure of the 17 restaurant chains with the highest brand value according to the Brand Finance 2020 ranking were measured with Altman Z Score, Altman Z' Score, Altman Z'' Score, Springate, Fulmer and Ohlson models between 2016 and 2020. As a result of the analysis, it was determined that the number of restaurants at risk of financial failure tends to increase as we approach the past to the present in all models. However, whether there is a statistically significant difference in the context of financial failure risk scores between the pre-Covid-19 epidemic (2016-2019) and the Covid-19 epidemic period (2020) was tested with the Wilcoxon Signed Rank Test. According to the results obtained, a statistically significant difference was found between the pre-Covid-19 epidemic and the epidemic period in terms of financial failure values in all models except the Ohlson model.