Search

'Thermal governance' has been discussed elsewhere as the regulation of temperature through infrastructure, technology and social and political organisation. We extend it here to include a subtle and heretofore under-recognised element of public health: the governance of recent urban epidemics by the Chinese state. The SARS epidemic of 2002–2003 in Guangzhou and more markedly the COVID-19 epidemic in Wuhan triggered massive emergency responses by public health authorities which differed from previous strategies in more fully activating the state health sector known in China as Chinese Medicine (zhongyi) and outside China as Traditional Chinese Medicine. With this enlistment comes a body of theory and practice which makes meteorology central to diagnostic and prescriptive processes, and reinforces as part of state discourse the long-standing Chinese cultural understanding of 'heat' as an internal micro-climatic element transcending temperature. [ABSTRACT FROM AUTHOR]

Social Impact Statement: Gingko biloba is an iconic tree with a surprising connection to the SARS and Covid viruses that have impacted human health since 2003. Natural history studies on the ecology of Gingko seed dispersal by Carnivoran scavengers in Asia over the past 30 plus years have elucidated the deep evolutionary history that not only makes these animals effective at spreading seeds but also predisposes them to become intermediate hosts for spreading diseases to humans. Understanding the behavioral traits that underlie these kinds of plant–animal interactions has the potential to help people limit the spread of future spillover diseases. Summary: Raccoon dogs and masked palm civets are Carnivoran scavengers native to Eastern Asia that have been documented feeding on the malodorous sarcotesta of Ginkgo biloba seeds and effectively dispersing the hard nuts they contain. Research has shown that their immune systems are genetically enhanced to protect them from the disease‐causing organisms they might pick up from their omnivorous diets that include live and dead animals. Both species are farmed for fur and meat across China and, up until recently, were commonly sold in "wet" markets. Research has determined that the palm civet played a role in spreading the SARS virus to humans in 2003 and that the raccoon dog may have played a similar role in spreading Covid in Wuhan in 2019, although this has not been proven. In areas where Ginkgo is cultivated, there are numerous internet reports of Carnivorans feeding on its seeds indicating that its dispersal strategy of attracting scavengers by mimicking the smell of carrion is adaptive and effective. [ABSTRACT FROM AUTHOR]

The SARS and COVID-19 pandemics represent the two largest economic shocks to human society in the past two decades. This paper investigates national economic resilience to these pandemics while 25 countries (region) and 46 countries are involved in the two studies, respectively. The study uses year-over-year quarterly economic growth data to measure the national economic resistance and economic recoverability in the recession-recovery cycles caused by the pandemics. The results show that: (i) the two pandemics caused evident economic fluctuations; (ii) there exists a negative relationship between economic resistance and economic recoverability across those infected countries; (iii) the typology of national economic resilience has shifted from weak resistance-good recoverability during the SARS period to good resistance-weak recoverability in the recent years of COVID-19; (iv) big variations of national economic policy response to the pandemic are found between high-income and middle-income countries. We call for building a more resilient world where sustainable and inclusive growth dominates the development pattern in the future. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome (SARS) and acute respiratory distress syndrome (ARDS) are often considered separate clinico-radiological entities. Whether these conditions also present a single process-specific systemic biomolecular phenotype and how this relates to patient outcomes remains unknown. A prospective cohort study was conducted, including adult patients admitted to the ICU and general floors for COVID-19-related (COVID+) or non-COVID-19-related (COVID−) acute respiratory failure during the main phase of the pandemic. The primary objective was to study blood biomarkers and outcomes among different groups and severity subsets. Results: A total of 132 patients were included, as follows: 67 COVID+, 54 COVID− (with 11 matched control subjects for biomarker reference), and 58 of these patients allowed for further pre- and post-analysis. The baseline apelin (APL) levels were higher in COVID+ patients (p < 0.0001 vs. COVID− patients) and in SARS COVID+ patients (p ≤ 0.02 vs. ARDS), while the IL-6 levels were higher in ARDS COVID− patients (p ≤ 0.0001 vs. SARS). Multivariable logistic regression analyses with cohort biomarkers and outcome parameters revealed the following: (i) log-transformed neprilysin (NEP) activity was significantly higher in COVID+ patients (1.11 [95% CI: 0.4–1.9] vs. 0.37 [95% CI: 0.1–0.8], fold change (FC): 1.43 [95% CI: 1.04–1.97], p = 0.029) and in SARS patients (FC: 1.65 [95% CI: 1.05–2.6], p = 0.032 vs. non-SARS COVID+ patients, and 1.73 [95% CI: 1.19–2.5], p = 0.005 vs. ARDS COVID− patients) and (ii) higher lysyl oxidase (LOX) activity and APL levels were respectively associated with death and a shorter length of hospital stay in SARS COVID+ patients (Odds Ratios (OR): 1.01 [1.00–1.02], p = 0.05, and OR: −0.007 [−0.013–0.0001], p = 0.048). Conclusion: Process-specific blood biomarkers exhibited distinct profiles between COVID+ and COVID− patients, and across stages of severity. NEP and LOX activities, as well as APL levels, are particularly linked to COVID+ patients and their outcomes (ClinicalTrials.gov Identifier: NCT04632732). [ABSTRACT FROM AUTHOR]

The synthesis of some new quinoxaline-1,2,4-oxadiazole-amide conjugates (6a–n) was described, and their structures were determined using 1HNMR, 13CNMR, and mass spectral analysis. The in vitro anti-cancer activity of the compounds (6a–n) against three human cancer cell lines such as MCF-7 (breast), HepG2 (lung), and DU-145 (prostate) revealed that the compounds 6d, 6e, and 6f exhibited promising activity against three cancer cell lines. Predominantly, compound 6f demonstrated greater activity than the standard drug Etoposide on MCF-7, HepG2, and DU-145 with IC50 values of 0.82 ± 0.01, 1.30 ± 0.02, and 2.12 ± 0.04 µM, respectively. Furthermore, the compounds 6e and 6f displayed promising inhibitory activity over the tyrosine kinase EGFR when compared with the standard Erlotinib. Molecular docking studies carried out on three potent compounds (6d, 6e, and 6f) on the EGFR receptor recommended that the compound 6f strongly binds to protein EGFR (pdbid: 4HJO). In addition, the in silico pharmacokinetic profile was also achieved for the three potent compounds 6d, 6e, and 6f using SWISS/ADME and pk CSM. Results showed that the compounds 6d, 6e, and 6f followed the Lipinski rule, Veber rule, Egan rule, Ghose rule, and Muegge rule without any deviation. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome (SARS) is a highly contagious viral disease with high mortality rate. There is no vaccine against SARS, but the spread can be limited by masking or social distancing. In this paper we implement a game-theoretic model of voluntary precautions against SARS. We build on the compartmental ODE model of the 2003 SARS epidemic. We assume that susceptible individuals can mask and/or limit contacts with others in order to decrease their chances of contracting SARS. Since the risk of SARS infection depends on the actions of others, this creates a public goods game. We find the Nash equilibrium, the solution of the game, which is the optimal voluntary level of precautions the individuals should take. We also study the effects of such actions on the spread of SARS and show that the effect significantly depends on the individual cost of the precautions. As soon as the cost rises above a critical threshold, the individuals will have no incentive to use any kind of voluntary precaution. [ABSTRACT FROM AUTHOR]

Police are omnipresent in Nigerian cities. The existence and actions of the Nigerian Police Force (NPF) in cities such as Lagos, Ibadan, and Abuja are intended like elsewhere in the urban world to deter, reduce, and solve crime. This is true of the Special Anti-Robbery Squad (SARS) of the NPF, created to combat armed robberies, car-snatchings, kidnappings, and cattle rustling. Its methods of seeking greater public security, however, raises questions about the fairness and efficacy of urban policing in Nigeria. Its reported police predation and violence during its stops, searches, detentions, and custody of urban denizens exacerbate socio-spatial injustices in Nigerian cities. We draw on the concept of the right to the city and qualitative data, including key informant interviews with Nigerian police, lawyers, and common city residents, including self-identified victims of SARS brutality, to describe how SARS helps us understand the context and characteristics of urban policing in Nigeria. [ABSTRACT FROM AUTHOR]

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1–28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

We studied SARS-CoV-2 binding and neutralizing antibody titers among previously infected persons in the United States over time. We assayed SARS-CoV-2 spike protein receptor-binding domain and neutralizing antibody titers for a convenience sample of residual clinical serum specimens that had evidence of prior SARS-CoV-2 infection gathered during January 2021–February 2022. We correlated titers and examined them by age group (65 years) across 4 different SARS-CoV-2 variant epochs. Among selected specimens, 30,967 had binding antibody titers and 744 had neutralizing titers available. Titers in specimens from children and adults correlated. In addition, mean binding antibody titers increased over time for all age groups, and mean neutralization titers increased over time for persons 16–49 and >65 years of age. Incorporating binding and neutralization antibody titers into infectious disease surveillance could provide a clearer picture of overall immunity and help target vaccination campaigns.

Social Impact Statement Gingko biloba is an iconic tree with a surprising connection to the SARS and Covid viruses that have impacted human health since 2003. Natural history studies on the ecology of Gingko seed dispersal by Carnivoran scavengers in Asia over the past 30 plus years have elucidated the deep evolutionary history that not only makes these animals effective at spreading seeds but also predisposes them to become intermediate hosts for spreading diseases to humans. Understanding the behavioral traits that underlie these kinds of plant–animal interactions has the potential to help people limit the spread of future spillover diseases. Summary Raccoon dogs and masked palm civets are Carnivoran scavengers native to Eastern Asia that have been documented feeding on the malodorous sarcotesta of Ginkgo biloba seeds and effectively dispersing the hard nuts they contain. Research has shown that their immune systems are genetically enhanced to protect them from the disease‐causing organisms they might pick up from their omnivorous diets that include live and dead animals. Both species are farmed for fur and meat across China and, up until recently, were commonly sold in “wet” markets. Research has determined that the palm civet played a role in spreading the SARS virus to humans in 2003 and that the raccoon dog may have played a similar role in spreading Covid in Wuhan in 2019, although this has not been proven. In areas where Ginkgo is cultivated, there are numerous internet reports of Carnivorans feeding on its seeds indicating that its dispersal strategy of attracting scavengers by mimicking the smell of carrion is adaptive and effective.

The Centers for Disease Control and Prevention defines SARS-CoV-2 reinfection as a positive COVID-19 test result >90 days after the collection date for the initial positive test or if sequencing confirms a different lineage is causing the reinfection. Reinfection dynamics have been examined by using PCR or antigen surveillance data. We identified patients in the US Military Health System who had >1 positive SARS-CoV-2 test during March 2020–July 2022 by using whole-genome sequencing data to identify reinfection cases, then compared those data with patient demographics, symptoms, and vaccination status. We identified 267 reinfections, of which 90% were caused by the SARS-CoV-2 Omicron variant. Reinfection symptom severity correlated with initial symptom severity and time since first infection. Furthermore, we found intrahost mutation rates varied greatly in 72 cases of continuing infections with the same variant. Continued investigations of reinfections caused by emerging SARS-CoV-2 variants of concern is needed to maintain US military readiness.

Abstract To verify if data obtained in the prehospital evaluation of patients with severe acute respiratory syndrome (SARS) during the initial response to the COVID-19 pandemic is associated with clinical outcomes: mechanical ventilation, hospital discharge, and death. This is a retrospective analysis involving secondary data from the Emergency Medical Service (EMS) records and the Health Surveillance Information System of patients assisted by the EMS in Manaus, from January to June 2020, the period of the first peak of COVID-19 cases. The combination of the two databases yielded a total of 1.190 patients, who received a first EMS response and were later admitted to hospital with SARS and had data on clinical outcomes of interest available. Patients were predominantly male (754, 63.4%), with a median age of 66 (IQR: 54.0–78.0) years. SARS illness before medical assistance was associated to need for invasive mechanical ventilation (IMV, p

Using participatory, virologic, and wastewater surveillance systems, we estimated when and to what extent reported data of adult COVID-19 cases underestimated COVID-19 incidence in Germany. We also examined how case underestimation evolved over time. Our findings highlight how community-based surveillance systems can complement official notification systems for respiratory disease dynamics.

The envelope (E) protein is present in all coronavirus genera. This protein can form pentameric oligomers with ion channel activity which have been proposed as a possible therapeutic target. However, high resolution structures of E channels are limited to those of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the recent COVID-19 pandemic. In the present work, we used Alphafold-2 (AF2), in ColabFold without templates, to predict the transmembrane domain (TMD) structure of six E-channels representative of genera alpha-, beta- and gamma-coronaviruses in the Coronaviridae family. High-confidence models were produced in all cases when combining multiple sequence alignments (MSAs) obtained from DeepMSA2. Overall, AF2 predicted at least two possible orientations of the α-helices in E-TMD channels: one where a conserved polar residue (Asn-15 in the SARS sequence) is oriented towards the center of the channel, ‘polar-in’, and one where this residue is in an interhelical orientation ‘polar-inter’. For the SARS models, the comparison with the two experimental models ‘closed’ (PDB: 7K3G) and ‘open’ (PDB: 8SUZ) is described, and suggests a ∼60˚ α-helix rotation mechanism involving either the full TMD or only its N-terminal half, to allow the passage of ions. While the results obtained are not identical to the two high resolution models available, they suggest various conformational states with striking similarities to those models. We believe these results can be further optimized by means of MSA subsampling, and guide future high resolution structural studies in these and other viral channels.

SARS-CoV-2 can infect wildlife, and SARS-CoV-2 variants of concern might expand into novel animal reservoirs, potentially by reverse zoonosis. White-tailed deer and mule deer of North America are the only deer species in which SARS-CoV-2 has been documented, raising the question of whether other reservoir species exist. We report cases of SARS-CoV-2 seropositivity in a fallow deer population located in Dublin, Ireland. Sampled deer were seronegative in 2020 when the Alpha variant was circulating in humans, 1 deer was seropositive for the Delta variant in 2021, and 12/21 (57%) sampled deer were seropositive for the Omicron variant in 2022, suggesting host tropism expansion as new variants emerged in humans. Omicron BA.1 was capable of infecting fallow deer lung type-2 pneumocytes and type-1–like pneumocytes or endothelial cells ex vivo. Ongoing surveillance to identify novel SARS-CoV-2 reservoirs is needed to prevent public health risks during human–animal interactions in periurban settings.

Objectives: The study involving 20 SARS CoV patients found that elevated microRNA levels, specifically miR-23a overexpression and miR-195-F1gene downregulation, could serve as potential diagnostic factors for COVID-19 infections, potentially aiding in early detection. Materials and Methods: 20 patients suffered from coronavirus (SARS CoV) (Patient group) and ten samples of healthy persons (control group). The blood sample was collected from the patients who attended Al-Zafaraniyah General Hospital, Fatima-Alzahra Hospital, and Al-Yarmook Teaching Hospital in Baghdad City. Nasopharyngeal and oropharyngeal swabs for each patient were taken simultaneously and added immediately into viral transport media (VTM). The microRNAs in the serum of coronavirus (SARS CoV patients were miRNA concentration upon conversion to cDNA is necessary to analyze and compute regulatory element levels of one or more genes—all procedures, including data analysis, qPCR amplification, and total RNA purification. Results: The miR-23a-3p levels were markedly elevated, and serum levels of the miR-195-F1 gene were shown to be substantially downregulated in COVID-19 individuals. Conclusions: The study reveals that COVID-19 patients exhibit increased expression levels of miR-23a-3p and miR-195-F1gene, suggesting it as a potential diagnostic indicator for COVID-19 diagnosis and treatment monitoring.

We conducted a serologic and molecular study to assess exposure of captive nonhuman primates (NHPs) to SARS-CoV-2 in Spain during the 2020–2023 COVID-19 pandemic. We found limited exposure of NHPs to SARS-CoV-2. Biosafety measures must be strictly maintained to avoid SARS-CoV-2 reverse-zoonotic transmission in the human–NHP interface.

COVID-19, caused by zoonotic coronavirus SARS-CoV-2, is not a first coronavirus infection, prior to this, two severe coronavirus infections were already faced by the humans at different parts of the world. COVID-19 is found to be more severe than its previous counterparts and cause respiratory syndrome along with some other pathophysiology effects. The main human protein which used by SARS causing coronavirus (SARS-CoV and SARS-CoV-2) is angiotensin-converting enzyme 2 (ACE2), a key member and regulator of RAS. Coronavirus shows a significant affinity with the ACE2, spike protein of the virus participate in this crucial interaction and initiate the infection cycle of the SARS. This ACE2 plays a very significant role in RAS, which directly affect the pathophysiology of humans, mainly of respiratory and cardiovascular diseases. Blockage or down-regulation of ACE2 can easily block the virus entry in the cells, but due to the other important role of the ACE2, the human system cannot afford its suppression or blockage. Due to its importance, it is required to understand the physiology and pathophysiological role of the ACE2, which can help to develop therapy against the SARS. This report provides a detailed account of ACE2, and help to understand about it, which will help to plan a possible way to fight against SARS-CoV-2 and other coronaviruses.

Introduction: The media can play a vital role in determining to what extent the general public understands scientific concepts. The understanding and acceptance of evolution are often influenced by factors beyond scientific knowledge alone, including education, politics, and media consumption habits. Although discussion of the COVID-19 pandemic and evolution had fixed itself in public discourse on many fronts, the media often avoided the usage of the word "evolve" and showed a preference for alternatives such as "emerge" or "mutate." Methods: We conducted a systematic analysis to gauge the prominence of the concept of evolution in media discussions across seven English-speaking countries. This involved assessing the frequency of the term "evolve" concerning viral evolution within newspaper articles using electronic databases. Of the 4,951 newspaper articles examined in this study, 11% discussed viral evolution. Out of those articles, 12% explicitly used the word "evolve." Results: We found that countries did not significantly differ in their "evolve" usage, which may reflect similarities in views about COVID-19 and its evolution across countries or reliance on shared information sources when reporting on COVID-19. We also found that, as the pandemic progressed, the discussion on viral evolution as a topic had increased, but the frequency with which the word "evolve" was explicitly used had decreased. Discussion: The COVID-19 pandemic has had a substantial impact on science and health news reporting. Although evolution plays a crucial role in the progression of the COVID-19 pandemic, the term "evolve" is not frequently highlighted in COVID-19 news coverage. Our research underscores the significant implications of language choice when describing evolutionary events, particularly in shaping the public's understanding of evolution, both in general and in the context of pandemics and infectious diseases. [ABSTRACT FROM AUTHOR]

COVID 19 pandemic is still ongoing, having taken more than 6 million human lives with it, and it seems that the world will have to learn how to live with the virus around. In consequence, there is a need to develop different treatments against it, not only with vaccines, but also new medicines. To do this, human-virus protein-protein interactions (PPIs) play a key part in drug-target discovery, but finding them experimentally can be either costly or sometimes unreliable. Therefore, computational methods arose as a powerful alternative to predict these interactions, reducing costs and helping researchers confirm only certain interactions instead of trying all possible combinations in the laboratory. Malivhu is a tool that predicts human-virus PPIs through a 4-phase process using machine learning models, where phase 1 filters ssRNA(+) class virus proteins, phase 2 filters Coronaviridae family proteins and phase 3 filters severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) species proteins, and phase 4 predicts human-SARS-CoV/SARS-CoV-2/MERS protein-protein interactions. The performance of the models was measured with Matthews correlation coefficient, F1-score, specificity, sensitivity, and accuracy scores, getting accuracies of 99.07%, 99.83%, and 100% for the first 3 phases, respectively, and 94.24% for human-SARS-CoV PPI, 94.50% for human-SARS-CoV-2 PPI, and 95.45% for human-MERS PPI on independent testing. All the prediction models developed for each of the 4 phases were implemented as web server which is freely available at https://kaabil.net/malivhu/. [ABSTRACT FROM AUTHOR]

A health crisis can impact GVCs adversely by raising bilateral trade costs and via supply‐ and demand‐side shocks in the exporting and importing countries. Focusing on trade in select GVC‐intensive sectors, we disentangle the effects of these different channels in the context of SARS and MERS in a structural gravity framework. The estimated effects are found to be small in magnitude and show significant heterogeneity by sector, channel and disease outbreak. SARS‐induced rise in bilateral trade costs is found to reduce the export value and number of products traded of both intermediate and final goods, while similar adverse effects from MERS are only observed on intermediate goods export value. There is more evidence for the adverse effects of supply‐shocks from both SARS and MERS in our results, while the expected negative effects of the demand‐shock are only observed for MERS. The SARS effects are found to diminish over time, pointing to resilience of the associated value‐chains. We also find suggestive evidence for SARS in particular being associated with geographical diversification and widening of value‐chains. [ABSTRACT FROM AUTHOR]

Objectives: The study involving 20 SARS CoV patients found that elevated microRNA levels, specifically miR-23a overexpression and miR-195-F1gene downregulation, could serve as potential diagnostic factors for COVID-19 infections, potentially aiding in early detection. Materials and Methods: 20 patients suffered from coronavirus (SARS CoV) (Patient group) and ten samples of healthy persons (control group). The blood sample was collected from the patients who attended Al-Zafaraniyah General Hospital, Fatima-Alzahra Hospital, and Al-Yarmook Teaching Hospital in Baghdad City. Nasopharyngeal and oropharyngeal swabs for each patient were taken simultaneously and added immediately into viral transport media (VTM). The microRNAs in the serum of coronavirus (SARS CoV patients were miRNA concentration upon conversion to cDNA is necessary to analyze and compute regulatory element levels of one or more genes—all procedures, including data analysis, qPCR amplification, and total RNA purification. Results: The miR-23a-3p levels were markedly elevated, and serum levels of the miR-195-F1 gene were shown to be substantially downregulated in COVID-19 individuals. Keywords: miR-23a, COV, SARS, qPCR, RT-PCR, cDNA, VTM. Conclusions: The study reveals that COVID-19 patients exhibit increased expression levels of miR-23a-3p and miR-195-F1gene, suggesting it as a potential diagnostic indicator for COVID-19 diagnosis and treatment monitoring. [ABSTRACT FROM AUTHOR]

Background: Iran has been one of the most affected countries in the world by COVID-19. The aim of our study was to determine the outcome of COVID-19 in patients with inflammatory bowel disease (IBD). Furthermore, we analyzed the outcome of SARS-CoV-2 infection in patients with IBD treated with immunosuppressant. Materials and Methods: This is a cross-sectional, observational study. This study included all patients with IBD, regularly followed up in our IBD Clinic at a tertiary medical center from February 5th, 2020 to August 5th, 2022. We identified those patients with confirmed SARS-CoV-2 infection either by PCR test or chest computed tomography (CT) imaging. Results: A total of 401 patients were recruited (n=346 [86.28%] with ulcerative colitis, n=53 [13.22%] with Crohn’s disease, and 2 [0.5%] with indeterminate colitis). Of these patients, 273 (68.08%) developed no symptoms or signs during the follow-up period,128 patients developed symptoms similar to COVID-19, and 76 (18.9%) were diagnosed as confirmed COVID-19 cases. Men comprised 60.5% of the confirmed COVID-19 groups, which shows that men were statistically more likely to have symptoms of COVID-19 during the follow-up period (P=0.04). No significant differences were observed among confirmed and non-COVID-19 cases in terms of concomitant medications: steroids (P=0.6), thiopurines (P=0.23), anti-TNF (P=0.23), and aminosalicylate (P=0.61). Three patients required hospitalization, but there were no admissions to the intensive care unit or deaths related to COVID-19. Conclusion: The risk of COVID-19-related adverse outcomes and death in patients with IBD is low. Also, patients with IBD under immunosuppressive treatment are not at an increased risk of COVID-19. [ABSTRACT FROM AUTHOR]

The RNA viruses SARS-CoV, SARS-CoV-2 and MERS-CoV encode the non-structural Nsp16 (2′-O-methyltransferase) that catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to the first ribonucleotide in mRNA. Recently, it has been found that breaking the bond between Nsp16 and SAM substrate results in the cessation of mRNA virus replication. To date, only a limited number of such inhibitors have been identified, which can be attributed to a lack of an effective "recipe". The aim of our study was to propose and verify a rapid and effective screening protocol dedicated to such purposes. We proposed four new indices describing structure-binding strength (structure–binding affinity, structure–hydrogen bonding, structure–steric and structure–protein–ligand indices) were then applied and shown to be extremely helpful in determining the degree of increase or decrease in binding affinity in response to a relatively small change in the ligand structure. After initial pre-selection, based on similarity to SAM, we limited the study to 967 compounds, so-called molecular chameleons. They were then docked in the Nsp16 protein pocket, and 10 candidate ligands were selected using the novel structure-binding affinity index. Subsequently the selected 10 candidate ligands and 8 known inhibitors and were docked to Nsp16 pockets from SARS-CoV-2, MERS-CoV and SARS-CoV. Based on the four new indices, the best ligands were selected and a new one was designed by tuning them. Finally, ADMET profiling and molecular dynamics simulations were performed for the best ligands. The new structure-binding strength indices can be successfully applied not only to screen and tune ligands, but also to determine the effectiveness of the ligand in response to changes in the target viral entity, which is particularly useful for assessing drug effectiveness in the case of alterations in viral proteins. The developed approach, the so-called chameleon strategy, has the capacity to introduce a novel universal paradigm to the field of drugs design, including RNA antivirals. [ABSTRACT FROM AUTHOR]

Definition: The Pandemic Equation describes multiple pandemic waves and has been applied to describe the COVID-19 pandemic. Using the generalized approaches of solid-state physics, we derive the Pandemic Equation, which accounts for the effects of pandemic mitigation measures and multiple pandemic waves. The Pandemic Equation uses slow and fast time scales for "curve flattening" and describing vaccination and mitigation measures and the Scaled Fermi–Dirac distribution functions for describing transitions between pandemic waves. The Pandemic Equation parameters extracted from the pandemic curves can be used for comparing different scenarios of the pandemic evolution and for extrapolating the pandemic evolution curves for the periods of time on the order of the instantaneous Pandemic Equation characteristic time constant. The parameter extraction for multiple locations could also allow for uncertainty quantification for such pandemic evolution predictions. [ABSTRACT FROM AUTHOR]

The corona virus disease-2019 (COVID-19) pandemic has affected most of the world with varying degrees of morbidity and mortality. The presence of genetic polymorphisms may be associated with the severity and outcome of COVID-19 infection. This work aimed to evaluate the genetic polymorphisms of interleukin (IL-6) and IL-10 genes with the outcome of COVID-19 infection. This cross-sectional study was conducted on 354 patients who were classified into moderate and severe cases (including alive and deceased cases). All individuals were genotyped for one SNP for IL-6 (rs1800795) and one SNP for IL10 (rs1800896) using allelic discrimination real-time PCR technique. In this study, 198 cases were moderate, and 156 cases were severe. The risk of allele carriage of the minor allele of IL-6 rs1800795 (C) was significantly higher among the severe group when compared with that of the moderate group (p < 0.0001), while there was a mild significant difference of same allele carriage among alive cases when compared to that of deceased one (p < 0.04). Furthermore, the risk of the C allele of IL-10 rs1800896 was significantly increased in severe cases when compared with the moderate group (p < 0.0001), while there was no significant difference of the risk of the C allele in deceased cases when compared with that of alive ones (p > 0.05). In conclusion, the C allele (rs1800795) of IL-6 and the C allele (rs1800896) of IL-10 were highly significant in severe cases than in moderate cases. The C allele carriage of IL-6 showed only a significant difference between alive and deceased patients and not with the C allele of IL-10. [ABSTRACT FROM AUTHOR]

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) remains a threat to pregnant women. However, the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood. Here, we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy. Compared to control placentas, SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection. However, subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface. Notably, the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester. Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Using the GISAID EpiCoV database, we identified 256 COVID-19 patients in Japan during March 31–December 31, 2023, who had mutations in the SARS-CoV-2 nonstructural protein 5 conferring ensitrelvir resistance. Ongoing genomic surveillance is required to monitor emergence of SARS-CoV-2 mutations that are resistant to anticoronaviral drugs.

The N-methyl-d-aspartate (NMDA) receptors, which belong to the ionotropic Glutamate receptors, constitute a family of ligand-gated ion channels. Within the various subtypes of NMDA receptors, the GluN1/2A subtype plays a significant role in central nervous system (CNS) disorders. The present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors, encompassing negative allosteric modulators (NAMs), positive allosteric modulators (PAMs) and competitive antagonists. Moreover, the ligands’ structure–activity relationships (SARs) and the binding models of representative ligands are also discussed, providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases.

Objective Health-care systems are facing a brand new difficulty as a result of post-COVID-19 syndrome. The relationship between long COVID and vitamin d.(25OHD levels was not extensively studied. Also, to our knowledge, no study evaluated vit d.(25OHD) levels and their relation to long COVID in the long-term period [3–6 months) after COVID infection. This study aims to evaluate vit d.(25OHD) levels post-COVID-19 infection and its relation to persistent symptoms in long-term COVID. Patients and methods A cross-sectional, single-center study involving 84 patients who were recruited during the period from December 2021 to May 2022, during the previous 6 months after the COVID-19 sickness. Complete history, clinical examination, and laboratory analysis [C-reactive protein, D-dimer, total leukocyte count, lymphocyte count. Serum vit d.(25OHD), and HRCT chest were performed. Results Of the patients, 44% had insufficient levels [20–30 ng/dL), 36% had deficient vitamin D levels [

The Pandemic Equation describes multiple pandemic waves and has been applied to describe the COVID-19 pandemic. Using the generalized approaches of solid-state physics, we derive the Pandemic Equation, which accounts for the effects of pandemic mitigation measures and multiple pandemic waves. The Pandemic Equation uses slow and fast time scales for “curve flattening” and describing vaccination and mitigation measures and the Scaled Fermi–Dirac distribution functions for describing transitions between pandemic waves. The Pandemic Equation parameters extracted from the pandemic curves can be used for comparing different scenarios of the pandemic evolution and for extrapolating the pandemic evolution curves for the periods of time on the order of the instantaneous Pandemic Equation characteristic time constant. The parameter extraction for multiple locations could also allow for uncertainty quantification for such pandemic evolution predictions.

The global COVID-19 pandemic illustrates the importance of a close partnership between public health and juvenile justice systems when responding to communicable diseases. Many setting-specific obstacles must be navigated to respond effectively to limit disease transmission and negative health outcomes while maintaining necessary services for youth in confinement facilities. The response requires multidisciplinary expertise and collaboration to address unique considerations. Public health mitigation strategies must balance the risk for disease against the negative effects of restrictions. Key aspects of the COVID-19 response in the juvenile justice system of Colorado, USA, involved establishing robust communication and data reporting infrastructures, building a multidisciplinary response team, adapting existing infection prevention guidelines, and focusing on a whole-person health approach to infection prevention. We examine lessons learned and offer recommendations on pandemic emergency response planning and managing a statewide public health emergency in youth confinement settings that ensure ongoing readiness.

Taiwan provided several COVID-19 vaccine platforms: mRNA (BNT162b2, mRNA-1273), adenoviral vector-based (AZD1222), and protein subunit (MVC-COV1901). After Taiwan shifted from its zero-COVID strategy in April 2022, population-based evaluation of vaccine effectiveness (VE) became possible. We conducted an observational cohort study of 21,416,151 persons to examine VE against SARS-CoV-2 infection, moderate and severe illness, and death during March 22, 2021–September 30, 2022. After adjusting for age and sex, we found that persons who completed 3 vaccine doses (2 primary, 1 booster) or received MVC-COV1901 as the primary series had the lowest hospitalization incidence (0.04–0.20 cases/100,000 person-days). We also found 95.8% VE against hospitalization for 3 doses of BNT162b2, 91.0% for MVC-COV1901, 81.8% for mRNA-1273, and 65.7% for AZD1222, which had the lowest overall VE. Our findings indicated that protein subunit vaccines provide similar protection against SARS-CoV-2­­–associated hospitalization as mRNA vaccines and can inform mix-and-match vaccine selection in other countries.

The N -methyl- d -aspartate (NMDA) receptors, which belong to the ionotropic Glutamate receptors, constitute a family of ligand-gated ion channels. Within the various subtypes of NMDA receptors, the GluN1/2A subtype plays a significant role in central nervous system (CNS) disorders. The present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors, encompassing negative allosteric modulators (NAMs), positive allosteric modulators (PAMs) and competitive antagonists. Moreover, the ligands' structure–activity relationships (SARs) and the binding models of representative ligands are also discussed, providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases. GluN1/2A subtype NMDA receptor plays a significant role in CNS disorders. This paper summarized GluN2A subtype selective antagonists, PAMs, and NAMs with their SARs and biological profiles. [Display omitted] [ABSTRACT FROM AUTHOR]

AbstractDue to their life cycle, viruses can disrupt the metabolism of their hosts, causing diseases. If we want to disrupt their life cycle, it is necessary to identify their presence. For this purpose, it is possible to use several molecular-biological and bioanalytical methods. The reference selection was performed based on electronic databases (2020–2023). This review focused on electrochemical methods with high sensitivity and selectivity (53% voltammetry/amperometry, 33% impedance, and 12% other methods) which showed their great potential for detecting various viruses. Moreover, the aforementioned electrochemical methods have considerable potential to be applicable for care-point use as they are portable due to their miniaturizability and fast speed analysis (minutes to hours), and are relatively easy to interpret. A total of 2011 articles were found, of which 86 original papers were subsequently evaluated (the majority of which are focused on human pathogens, whereas articles dealing with plant pathogens are in the minority). Thirty-two species of viruses were included in the evaluation. It was found that most of the examined research studies (77%) used nanotechnological modifications. Other ones performed immunological (52%) or genetic analyses (43%) for virus detection. 5% of the reports used peptides to increase the method’s sensitivity. When evaluable, 65% of the research studies had LOD values in the order of ng or nM. The vast majority (79%) of the studies represent proof of concept and possibilities with low application potential and a high need of further research experimental work. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) has gaining potential, and very effective to curb or deactivate the various microorganisms such as bacteria and virus. Lately, the major outbreak SARS-CoV-2 infection has affected humanity largely with added complexity of its ability to mutate to variants such as Omicron. We have earlier shown the effectiveness of CAP on SARS-CoV-2 spike protein and, in this study, we have evaluated the effectiveness of CAP to deactivate Omicron. We studied the ability of the binding of Angiotensin converting Enzyme Protein (ACE2) protein to the plasma treated spike S1-S2 protein and spike Receptor binding domain (RBD) using Cold atmospheric plasma direct treatment as well as Plasma activated water (PAW). Results have shown the binding efficiency of Omicron spike protein to ACE2 decrease with increase in treatment time with both direct treatment and PAW as evidenced using spectroscopic techniques. The reactive species (RONS) play a major role in the efficient deactivation of the binding of ACE2 to the Omicron spike protein. Correspondingly, the comparison between the efficiency between direct treatment and PAW has also been discussed. [ABSTRACT FROM AUTHOR]

Coronaviruses have caused three severe epidemics since the start of the 21st century: SARS, MERS and COVID-19. The severity of the ongoing COVID-19 pandemic and increasing likelihood of future coronavirus outbreaks motivates greater understanding of factors leading to severe coronavirus disease. We screened ten strains from the Collaborative Cross mouse genetic reference panel and identified strains CC006/TauUnc (CC006) and CC044/Unc (CC044) as coronavirus-susceptible and resistant, respectively, as indicated by variable weight loss and lung congestion scores four days post-infection. We generated a genetic mapping population of 755 CC006xCC044 F2 mice and exposed the mice to one of three genetically distinct mouse-adapted coronaviruses: clade 1a SARS-CoV MA15 (n=391), clade 1b SARS-CoV-2 MA10 (n=274), and clade 2 HKU3-CoV MA (n=90). Quantitative trait loci (QTL) mapping in SARS-CoV MA15- and SARS-CoV-2 MA10-infected F2 mice identified genetic loci associated with disease severity. Specifically, we identified seven loci associated with variation in outcome following infection with either virus, including one, HrS43, that is present in both groups. Three of these QTL, including HrS43, were also associated with HKU3-CoV MA outcome. HrS43 overlaps with a QTL previously reported by our lab that is associated with SARS-CoV MA15 outcome in CC011xCC074 F2 mice and is also syntenic with a human chromosomal region associated with severe COVID-19 outcomes in humans GWAS. The results reported here provide: (a) additional support for the involvement of this locus in SARS-CoV MA15 infection, (b) the first conclusive evidence that this locus is associated with susceptibility across the Sarbecovirus subgenus, and (c) demonstration of the relevance of mouse models in the study of coronavirus disease susceptibility in humans.

Here we report an ultrafast quadruplex RT-qPCR assay with robust diagnostic ability to detect and distinguish pan-SARS-CoVs and influenza A/B viruses within 35 min. This quadruplex RT-qPCR assay comprised of one novel RNA-based internal control targeting human β2-microglobulin (B2M) for process accuracy and three newly-designed primers-probe sets targeting the envelope protein (E) of pan-SARS-CoV, matrix protein (MP) of influenza A virus and non-structural (NS) region of influenza B virus. This quadruplex assay exhibited a sensitivity comparable to its singleplex counterparts and a slightly higher to that of the Centers for Disease Control and Prevention-recommended SARS-CoV-2 and influenza A/B assays. The novel assay showed no false-positive amplifications with other common respiratory viruses, and its 95 % limits of detection for pan-SARS-CoV and influenza A/B virus was 4.26–4.52 copies/reaction. Moreover, the assay was reproducible with less than 1 % coefficient of variation and adaptable testing different clinical and environmental samples. Our ultrafast quadruplex RT-qPCR assay can serve as an attractive tool for effective differentiation of influenza A/B virus and SARS-CoV-2, but more importantly prognose the reemergence/emergence of SARS and novel coronaviruses or influenza viruses from animal spillover.

Beginning in early 2020, SARS-CoV-2, the virus responsible for COVID-19, spread across the world, giving rise to a global pandemic that impacted billions of people. Surprisingly, the United States was among one of the worst affected countries with over a million deaths. The purpose of this review is to discuss the impact of COVID-19 in the United States from the perspectives of government policies and the U.S. healthcare system. The emergence of multiple viral variants was at the center of sequential waves of infection in the U.S., resulting in increased number of cases, hospitalizations, and deaths along with associated mental health sequelae in the population. Lack of uniform policies at the local, state, and federal levels exacerbated the situation. These factors contributed to significant healthcare worker burnout. Furthermore, the disease caused higher morbidity and mortality rates in specific groups such as lower average socioeconomic status, rural and underserved communities, Native Americans and African Americans, and older age groups (65+ years). The lessons learned from this broad analysis highlight many inadequacies and challenges experienced in the U.S. during the pandemic. Here we propose several suggestions for healthcare and government responses in the event of future unanticipated healthcare crises.