Raman and fourier transform infrared spectroscopy techniques for detection of coronavirus (COVID-19): a mini review.

Coronavirus pandemic has been a huge jeopardy to human health in various systems since it outbroke, early detection and prevention of further escalation has become a priority. The current popular approach is to collect samples using the nasopharyngeal swab method and then test for RNA using the real-time polymerase chain reaction, which suffers from false-positive results and a longer diagnostic time scale. Alternatively, various optical techniques, namely, optical sensing, spectroscopy, and imaging shows a great promise in virus detection. In this mini review, we briefly summarize the development progress of vibrational spectroscopy techniques and its applications in the detection of SARS-CoV family. Vibrational spectroscopy techniques such as Raman spectroscopy and infrared spectroscopy received increasing appreciation in bio-analysis for their speediness, accuracy and cost-effectiveness in detection of SARS-CoV. Further, an account of emerging photonics technologies of SARS-CoV-2 detection and future possibilities is also explained. The progress in the field of vibrational spectroscopy techniques for virus detection unambiguously show a great promise in the development of rapid photonics-based devices for COVID-19 detection.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

TMPRSS2 Inhibitor Discovery Facilitated through an In Silico and Biochemical Screening Platform.

The COVID-19 pandemic has highlighted the need for new antiviral approaches because many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections. The host transmembrane serine protease TMPRSS2 is a promising antiviral target because it plays a role in priming the spike protein before viral entry occurs for the most virulent variants. Further, TMPRSS2 has no established physiological role, thereby increasing its attractiveness as a target for antiviral agents. Here, we utilize virtual screening to curate large libraries into a focused collection of potential inhibitors. Optimization of a recombinant expression and purification protocol for the TMPRSS2 peptidase domain facilitates subsequent biochemical screening and characterization of selected compounds from the curated collection in a kinetic assay. In doing so, we identify new noncovalent TMPRSS2 inhibitors that block SARS-CoV-2 infectivity in a cellular model. One such inhibitor, debrisoquine, has high ligand efficiency, and an initial structure-activity relationship study demonstrates that debrisoquine is a tractable hit compound for TMPRSS2.

Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.

The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.

The Screening of Broadly Neutralizing Antibodies Targeting the SARS-CoV-2 Spike Protein by mRNA Immunization in Mice.

Neutralizing antibodies (nAbs), the popular antiviral drugs used for the treatment of COVID-19, are effective in reducing viral load and hospitalization. Currently, most nAbs are screened from convalescent or vaccinated individuals through single B-cell sequencing which requires cutting-edge facilities. Moreover, owing to the rapid mutation of SARS-CoV-2, some approved nAbs are no longer effective. In the present study, we designed a new approach to acquiring broadly neutralizing antibodies (bnAbs) from mRNA-vaccinated mice. Using the flexibility and speed of mRNA vaccine preparation, we designed a chimeric mRNA vaccine and sequential immunization strategies to acquire bnAbs in mice within a short period. By comparing different vaccination orders, we found that the initially administered vaccine had a greater effect on the neutralizing potency of mouse sera. Ultimately, we screened a strain of bnAb that neutralized wild-type, Beta, and Delta SARS-CoV-2 pseudoviruses. We synthesized the mRNAs of the heavy and light chains of this antibody and verified its neutralizing potency. This study developed a new strategy to screen for bnAbs in mRNA-vaccinated mice and identified a more effective immunization strategy for inducing bnAbs, providing valuable insights for future antibody drug development.

Uniform Gold Nanostructure Formation via Weakly Adsorbed Gold Films and Thermal Annealing for Reliable Localized Surface Plasmon Resonance-Based Detection of DNase-I.

Deoxyribonuclease-I (DNase-I), a representative endonuclease, is an important biomarker for the diagnosis of infectious diseases and cancer progression. However, enzymatic activity decreases rapidly ex vivo, which highlights the need for precise on-site detection of DNase-I. Here, a localized surface plasmon resonance (LSPR) biosensor that enables the simple and rapid detection of DNase-I is reported. Moreover, a novel technique named electrochemical deposition and mild thermal annealing (EDMIT) is applied to overcome signal variations. By taking advantage of the low adhesion of gold clusters on indium tin oxide substrates, both the uniformity and sphericity of gold nanoparticles are increased under mild thermal annealing conditions via coalescence and Ostwald ripening. This ultimately results in an approximately 15-fold decrease in LSPR signal variations. The linear range of the fabricated sensor is 20-1000 ng mL-1 with a limit of detection (LOD) of 127.25 pg mL-1 , as demonstrated by spectral absorbance analyses. The fabricated LSPR sensor stably measured DNase-I concentrations from samples collected from both an inflammatory bowel disease (IBD) mouse model, as well as human patients with severe COVID-19 symptoms. Therefore, the proposed LSPR sensor fabricated via the EDMIT method can be used for early diagnosis of other infectious diseases.

The importance of equally accessible genomic surveillance in the age of pandemics.

Genomic epidemiology is now a core component in investigating the spread of a disease during an outbreak and for future preparedness to tackle emerging zoonoses. During the last decades, several viral diseases arose and emphasized the importance of molecular epidemiology in tracking the dispersal route, supporting proper mitigation measures, and appropriate vaccine development. In this perspective article, we summarized what has been done so far in the genomic epidemiology field and what should be considered in the future. We traced back the methods and protocols employed over time for zoonotic disease response. Either to small outbreaks such as the severe acute respiratory syndrome (SARS) outbreak identified first in 2002 in Guangdong, China, or to a global pandemic like the one that we are experiencing now since 2019 when the severe acute respiratory syndrome 2 (SARS-CoV-2) virus emerged in Wuhan, China, following several pneumonia cases, and subsequently spread worldwide. We explored both the benefits and shortages encountered when relying on genomic epidemiology, and we clearly present the disadvantages of inequity in accessing these tools around the world, especially in countries with less developed economies. For effectively addressing future pandemics, it is crucial to work for better sequencing equity around the globe.

Screening compounds for treating the diabetes and COVID-19 from Miao medicine by molecular docking and bioinformatics.

Both diabetes and Corona Virus Disease 2019 (COVID-19) are seriously harmful to human health, and they are closely related. It is of great significance to find drugs that can simultaneously treat diabetes and COVID-19. Based on the theory of traditional Chinese medicine for treating COVID-19, this study first sorted out the compounds of Guizhou Miao medicine with "return to the lung channel" and "clear heat and detoxify" effects in China. The active components against COVID-19 were screened by molecular docking with SARS-CoV-2 PLpro and angiotensin-converting enzyme II as targets. Furthermore, the common target dipeptidyl peptidase 4 (DPP4) of diabetes and COVID-19 was used as a screening protein, and molecular docking was used to obtain potential components for the treatment of diabetes and COVID-19. Finally, the mechanism of potential ingredients in the treatment of diabetes and COVID-19 was explored with bioinformatics. More than 80 kinds of Miao medicine were obtained, and 584 compounds were obtained. Further, 110 compounds against COVID-19 were screened, and top 6 potential ingredients for the treatment of diabetes and COVID-19 were screened, including 3-O-ß-D-Xylopyranosyl-(1-6)-ß-D-glucopyranosyl-(1-6)-ß-D-glucopyranosyl oleanolic acid 28-O-ß-D-glucopyranosyl ester, Glycyrrhizic acid, Sequoiaflavone, 2-O-Caffeoyl maslinic acid, Pholidotin, and Ambewelamide A. Bioinformatics analysis found that their mechanism of action in treating diabetes and COVID-19 may be related to regulating the expression of DPP4, angiotensin II type 1 receptor, vitamin D receptor, plasminogen, chemokine C-C-motif receptor 6, and interleukin 2. We believe that Guizhou Miao medicine is rich in potential ingredients for the treatment of diabetes and COVID-19.

[Hospitalary concurrent exercise program in overweight and obese school students and adolescents during COVID-19 pandemic]. / Programa de ejercicio concurrente hospitalario en escolares y adolescentes con sobrepeso y obesidad durante la pandemia COVID-19.

The COVID-19 pandemic reduced daily physical activity in the pediatric population, with deleterious effects on anthropometry, muscle function, aerobic capacity, and metabolic control. OBJECTIVE: Determine the changes in anthropometry, aerobic capacity, muscle function, and metabolic control of a 12-week concurrent training protocol in overweight and obese children and adolescents during the COVID-19 pandemic. PATIENTS AND METHOD: 24 patients participated and were divided into groups once a week (12S; n = 10) and twice a week (24S; n = 14). Anthropometry, muscle function, aerobic capacity, and metabolic biochemical tests were evaluated before and after the application of the concurrent training plan. Two-way ANOVA, Kruskal-Wallis test, and Fisher's post hoc test were used. RESULTS: Only the twice times week training improved the anthropometrics parameters (BMI - z, waist circumference and waist to height ratio). The muscle function tests (push up, standing broad jump and prone plank), improved in both groups such as the aerobic capacity measured by VO2maximo and the runned distance in Shuttle 20m run test. The HOMA index only improved with twice times week training without changes in lipid profile in both groups. CONCLUSIONS: The 12S and 24S groups improved aerobic capacity and muscular function. Only the 24S improved anthropometric parameters and the HOMA index.

[Analysis with Google Trends and Our World in Data on Global Mental Health in the Context of the covid-19 Pandemic]. / Análisis con Google Trends y Our World in Data sobre la salud mental mundial en el contexto de la pandemia por covid-19.

Introduction: During the covid-19 pandemic, mental health services were unable to cope with the high demand from the population, so many people chose to search the Internet for information that could help them cope with the psychological process they were experiencing at the time. The aim of this study was to characterize the global search trend for the term «psychiatry¼ in the context of covid-19 using Google Trends and Our World in Data. Methods: Descriptive-cross-sectional study on global search trends for Psychiatry in the context of covid-19 under the terms «psychiatry¼, «depression¼, «anxiety¼, «stress¼, «insomnia¼ and «suicide¼ in the category of health, this was conducted over the period 2020-2021 and time graphs were generated. Results: The term «psychiatry¼ remained at a consistently high relative search volume (between 60 and 90), with a significant and gradual search in the month of April. The relative search volume for «depression¼, «anxiety¼ and «stress¼ remained constant with some non-significant fluctuations over the period 2020-2021. The term «insomnia¼ was predominant between January and June 2020, gradually declining in April and remaining constant until October 2021. Finally, the term «suicide¼ had a fluctuating RBV between 60 and 100 during this period. Conclusions: During the study period, the topics related to mental health and the speciality of psychiatry remained constant, with some fluctuating, but not outstanding variations.

Identifying potent inhibitory phytocompounds from Lagerstroemia speciosa against SARS-Coronavirus-2: structure-based virtual screening.

The ongoing spillover of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for expedited countermeasure through developing therapeutics from natural reservoirs and/or the use of less time-consuming drug discovery methodologies. This study aims to apply these approaches to identify potential blockers of the virus from the longstanding medicinal herb, Lagerstroemia speciosa, through comprehensive computational-based screening. Nineteen out of 22 L. speciosa phytochemicals were selected on the basis of their pharmacokinetic properties. SARS-CoV-2 Main protease (Mpro), RNA-directed RNA polymerase (RdRp), Envelope viroporin protein (Evp) and receptor-binding domain of Spike glycoprotein (S-RBD), as well as the human receptor Angiotensin-converting enzyme-2 (hACE2) were chosen as targets. The screening was performed by molecular docking, followed by 100-ns molecular dynamic simulations and free energy calculations. 24-Methylene cycloartanol acetate (24MCA) was found as the best inhibitor for both Evp and RdRp, and sitosterol acetate (SA) as the best hit for Mpro, S-RBD and hACE2. Dynamic simulations, binding mode analyses, free energy terms and share of key amino acids in protein-drug interactions confirmed the stable binding of these phytocompounds to the hotspot sites on the target proteins. With their possible multi-targeting capability, the introduced phytoligands might offer promising lead compounds for persistent fight with the rapidly evolving coronavirus. Therefore, experimental verification of their safety and efficacy is recommended.

An appeal for strengthening genomic pathogen surveillance to improve pandemic preparedness and infection prevention: the German perspective.

The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance. Planning, establishing and consistently supporting adequate structures for genomic pathogen surveillance will be crucial to identify and combat future pandemics as well as other challenges in infectious diseases such as multi-drug resistant bacteria and healthcare-associated infections. Therefore, the authors propose a multifaceted and coordinated process for the definition of procedural, legal and technical standards for comprehensive genomic pathogen surveillance in Germany, covering the areas of genomic sequencing, data collection and data linkage, as well as target pathogens. A comparative analysis of the structures established in Germany and in other countries is applied. This proposal aims to better tackle epi- and pandemics to come and take action from the "lessons learned" from the SARS-CoV-2 pandemic.

Identification of potential Indonesian marine invertebrate bioactive compounds as TMPRSS2 and SARS-CoV-2 Omicron spike protein inhibitors through computational screening.

The coronavirus pandemic led to the announcement of a worldwide health emergency. The SARS-CoV-2 Omicron variant, which swiftly spread worldwide, has fueled existing challenges. Appropriate medication is necessary to avoid severe SARS-CoV-2 disease. The human TMPRSS2 and SARS-CoV-2 Omicron spike protein, which are required for viral entry into the host phase, were identified as the target proteins through computational screening. Structure-based virtual screening; molecular docking; absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis; and molecular dynamics simulation were the methods applied for TMPRSS2 and spike protein inhibitors. Bioactive marine invertebrates from Indonesia were employed as test ligands. Camostat and nafamostat (co-crystal) were utilized as reference ligands against TMPRSS2, whereas mefloquine was used as a reference ligand against spike protein. Following a molecular docking and dynamics simulation, we found that acanthomanzamine C has remarkable effectiveness against TMPRSS2 and spike protein. Compared to camostat (-8.25 kcal/mol), nafamostat (-6.52 kcal/mol), and mefloquine (-6.34 kcal/mol), acanthomanzamine C binds to TMPRSS2 and spike protein with binding energies of -9.75 kcal/mol and -9.19 kcal/mol, respectively. Furthermore, slight variances in the MD simulation demonstrated consistent binding to TMPRSS2 and spike protein after the initial 50 ns. These results are highly valuable in the search for a treatment for SARS-CoV-2 infection.

Corrigendum to ?Repurposing FDA-approved drugs to fight COVID-19 using in silico methods: Targeting SARS-CoV-2 RdRp enzyme and host cell receptors (ACE2, CD147) through virtual screening and molecular dynamic simulationsË® [Inform. Med. Unlocked 23 (2021) 1-9/100541].

[This corrects the article DOI: 10.1016/j.imu.2021.100541.].

Novel Approaches in the Management of Mucormycosis.

Purpose of Review: Invasive mucormycosis (IM), caused by fungi of the order Mucorales, is one of the deadliest fungal infection among hematologic cancer patients. Its incidence is also increasingly reported in immunocompetent individuals, notably with the COVID-19 pandemic. Therefore, there is an urgent need for novel diagnostic and therapeutic approaches of IM. This review discusses the current advances in this field. Recent Findings: Early diagnosis of IM is crucial and can be improved by Mucorales-specific PCR and development of lateral-flow immunoassays for specific antigen detection. The spore coat proteins (CotH) are essential for virulence of the Mucorales and may represent a target for novel antifungal therapies. Adjuvant therapies boosting the immune response, such as interferon-γ, anti-PDR1 or fungal-specific chimeric antigen receptor (CAR) T-cells, are also considered. Summary: The most promising perspectives for improved management of IM consist of a multilayered approach targeting both the pathogen and the host immune system.

[Resilience, anxiety and stress among formal caregivers for institutionalized older people]. / Resiliencia, estrés y ansiedad de cuidadores formales durante la pandemia por COVID-19.

BACKGROUND: Caregiver stress is a common problem observed in nursing homes. AIM: To determine the association between the level of resilience and stress, anxiety and depression in formal caregivers of older people institutionalized in long-stay establishments during the COVID-19 pandemic. MATERIAL AND METHODS: One hundred ninety eight formal caregivers working at 11 long term residences for older people in southern Chile were invited to answer the SV-RES resilience and the DASS-21 anxiety and depression scales and 102 agreed to participate. RESULTS: We observed a significant association between the resilience scale score and variables such as weekly working hours (p < 0.01), current hours of sleep (p < 0.01), self-perception of sleep (p < 0.01), anxiety level (p < 0.01) and stress level (p < 0.01). CONCLUSIONS: A higher score on the Resilience Scale was associated with the absence of anxiety and stress, working between 22 and 43 hours per week, sleeping between 7 and 8 hours of sleep and a satisfactory self-perception of sleep. Studying the factors associated with resilience in formal caregivers of the elderly allows healthcare personnel to focus preventive actions, intervening promptly in risk areas associated with the work context, and strengthening the personal resources of caregivers.

A Strategy Formulation Framework for Efficient Screening during the Early Stage of a Pandemic.

For viruses that can be transmitted by contacts of people, efficiently screening infected individuals is beneficial for controlling outbreaks rapidly and avoiding widespread diffusion, especially during the early stage of a pandemic. The process of virus transmission can be described as virus diffusion in complex networks such as trajectory networks. We propose a strategy formulation framework (SFF) for generating various screening strategies to identify influential nodes in networks. We propose two types of metrics to measure the nodes' influence and three types of screening modes. Then, we can obtain six combinations, i.e., six strategies. To verify the efficiencies of the strategies, we build a scenario model based on the multi-agent modelling. In this model, people can move according to their self-decisions, and a virtual trajectory network is generated by their contacts. We found that (1) screening people will have a better performance based on their contact paths if there is no confirmed case yet, and (2) if the first confirmed case has been discovered, it is better to screen people sequentially by their influences. The proposed SFF and strategies can provide support for decision makers, and the proposed scenario model can be applied to simulate and forecast the virus-diffusion process.