Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants can escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent COVID-19 patient, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 Wuhan, alpha, beta, gamma and delta infection in vitro . In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 μg/ml, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs.

Background: Pandemics restrict access to reproductive healthcare services and worsen the inequalities in the delivery of healthcare services. This descriptive, cross-sectional study was performed to examine the effects of the COVID-19 pandemic on women’s reproductive health protective attitudes. Methods: : The study sample included 306 women and data were collected through a web-based, online questionnaire. The data were collected using the Personal Information Form, Determination of Married Women's Reproductive Health Protective Attitudes Scale. Descriptive statistics, independent samples t-test, ANOVA test were used to assess the data. Results: : The mean scores for Determination of Married Women's Reproductive Health Protective Attitudes Scale significantly differed in terms of education, employment status, income, health insurance and perceived health status (p<0.05). Sixty-nine-point-three percent of the women had their first pregnancy at the agerange of 21-34 years, 17.6% of the women had four or more pregnancies, 55.6% of the women gave birth 1-3 times, 13.4% of the women gave birth at home and 57.8% of the women did not use an effective contraceptive. Twenty-three-point-two percent of the women experienced a problem with their reproductive organs during the pandemic, 70.6% of them did not present to a health center for their problems and 74.5% of these women did not present to a health center to avoid the risk of COVID-19 transmission. Forty-point-two percent of the women used the methods they already know at home to relieve their problems and 16.0% of the women used them edications previously prescribed by their doctors. Conclusion: The pandemic negatively affects there productive health of women. While health policies are modified to meet increased healthcare demands from COVID-19 patients and to eliminate the threat of the pandemic. The role of midwives and nurses is very important in the maintenance of reproductive health services.

COVID-19 pandemic has claimed millions of lives and devastated the health service system, livelihood and economy in many countries worldwide. Despite the initiation of vaccination programs in many countries, the spread of the pandemic continues and effective treatment is still urgently needed. Although some antiviral drugs have been shown to be effective, they are not widely available. Repurposing of anti-parasitic drugs with in vitro anti-SARS-CoV-2 activity is a promising approach being tested in many clinical trials. Combination of these drugs is a plausible way to enhance their effectiveness. We tested in vitro anti-SARS-CoV-2 activity of combinations of Niclosamide, Ivermectin, and Chloroquine; and show here that these combinations resulted in more than 10-fold reduction in the half maximal inhibitory concentration (IC 50 ) as compared to individual drugs. Synergy landscape analyses showed Niclosamide-Ivermectin combination to have the best synergy score with a peak Loewe synergy score of over 20 and a mean score of 6.60 in Vero E6 cell and a peak Loewe synergy score of 13.2 and a mean score of 2.897 in Calu-3 cells.

ABSTRACT Zika virus (ZIKV) serine protease, indispensable for viral polyprotein processing and replication, is composed of the membrane-anchored NS2B polypeptide and the N-terminal domain of the NS3 polypeptide (NS3pro). The C-terminal domain of the NS3 polypeptide (NS3hel) is necessary for helicase activity and contains an ATP-binding site. We discovered that ZIKV NS2B-NS3pro can bind single-stranded RNA with a K d of ∼0.3 μM, suggesting a novel function. We tested various structural modifications of NS2B-NS3pro and observed that constructs stabilized in the recently discovered “super-open” conformation do not bind RNA. Likewise, stabilization of NS2B-NS3pro in the “closed” (proteolytically active) conformation using substrate inhibitors abolished RNA binding. We posit that RNA binding occurs when ZIKV NS2B-NS3pro adopts the “open” conformation, which we modeled using highly homologous dengue NS2B-NS3pro crystallized in the open conformation. We identified two positively charged fork-like structures present only in the open conformation of NS3pro. These forks are conserved across Flaviviridae family and could be aligned contiguously with the positively charged grove on NS3hel that binds RNA. This led us to propose the “reverse inchworm” model for a tightly intertwined NS2B-NS3 helicase-protease machinery, which suggests that the cycles of NS2B-NS3pro binding and releasing RNA enable the unlimited processivity of NS3hel. The transition to the closed conformation, likely induced by the substrate, enables the classical protease activity of NS2B-NS3pro.

Flaviviruses are enveloped, positive-strand RNA viruses that cause millions of infections in the human population annually. Although Zika virus (ZIKV) had been detected in humans as early as the 1950s, its reemergence in South America in 2015 resulted in a global health crisis. While flaviviruses encode 10 proteins that can be post-translationally modified by host enzymes, little is known regarding post-translational modifications (PTMs) of the flavivirus proteome. We used mass spectrometry to comprehensively identify host-driven PTMs on the ZIKV proteome. This approach allowed us to identify 43 PTMs across 8 ZIKV proteins, including several that are highly conserved within the Flavivirus genus. Notably, we found two phosphosites on the ZIKV envelope protein that are functionally important for viral propagation and appear to regulate viral budding. Additionally, we discovered 115 host kinases that interacted with ZIKV proteins and determined that Bosutinib, an FDA-approved tyrosine kinase inhibitor that targets ZIKV interacting host kinases, impairs ZIKV growth. Thus, we have defined a high-resolution map of host-driven PTMs on ZIKV proteins as well as cellular interacting kinases, uncovered a novel mechanism of host driven-regulation of ZIKV budding, and identified an FDA-approved inhibitor of ZIKV growth.

The outbreak of the coronavirus 2019 (COVID-19) has created an excellent challenge for the care system worldwide. One in every of the foremost vital points of this challenge is that the management of COVID-19 patients needing acute and/or vital metastasis care. The main objective of applying data mining to Covid-19 dataset is essential to propel learning by empowering data-oriented decision making to improve existing clinical practices and learning materials. Current data mining techniques offer patient data analysis for achieving an automated diagnosis of the diseases as an example; however, the results are not very accurate nor reliable, especially with a dynamic virus as the COVID-19. In this paper, we are proposing a multi-stage diagnostic ( MSD-Covid19 ) model to enhance the diagnosis of the COVID-19, and to provide a sustainable automated system to improve the healthcare systems and patient outcomes. The first stage includes a selection of a classification model with no reduction attributes. Tested classification algorithms include Deep learning, Multilayer Perceptron, KNN, Bayesian Auto Regression, Logistic Model Trees (LMT), Hoeffding tree (VFDT), and Fuzzy Unordered Rule Induction Algorithm. In the second stage, a rough set reduction algorithm based on genetic algorithms is employed, and finally, an optimization of the classification is conducted using the reduced attributes. The proposed model is evaluated on a global COVID-19 dataset. Experimental results demonstrate that the proposed MSD-Covid19 has a great contribution to increase the diagnostic accuracy of the COVID-19 disease behaviour.

Background: Testosterone is an important hormone affecting human growth and development. Recent studies have shown that testosterone is related to immune regulation. Infection with Zika virus (ZIKV) can cause testicular damage and decrease testosterone secretion. However, whether testosterone plays a function in the pathogenesis of ZIKV is still unclear. The main objective of this study was to understand the role of testosterone in central nervous system injury and inflammation induced by ZIKV. Methods: : In this work, a mouse model was used to evaluate the role of testosterone in ZIKV infection. Histopathological analysis, flow cytometry, and real-time PCR were performed to investigate the mechanism by which testosterone improved survival in mice after ZIKV infection. Results: : ZIKV infection caused testicular damage and decreased testosterone secretion in mice, and testosterone supplementation after ZIKV infection reduced mortality and pathological symptoms in mice. Histopathological analysis showed that testosterone treatment after ZIKV infection could reduce inflammatory cell infiltration in the brain and alleviate brain injury. Flow cytometry and quantitative real-time PCR results confirmed that testosterone treatment could reduce the CD8 + T cell infiltration and the expression of interferon gamma and inflammatory cytokines induced by ZIKV. Conclusion: Testosterone plays an important protective role in mice during ZIKV infection and can be used as a potential therapeutic treatment for ZIKV infection.

Summary Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM responses contribute to ZIKV immunity in pregnancy, mediating neutralization up to three months post symptoms. From a ZIKV-infected pregnant woman, we established a B cell line secreting a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets a novel envelope dimer epitope within Domain II. The arrangement of this epitope on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not achievable by IgG antibodies. DH1017.IgM protected against lethal ZIKV challenge in mice. Our findings identify a unique role of antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunoprophylactic, particularly during pregnancy. Key points Plasma IgM contributes to early ZIKV neutralization during pregnancy Ultrapotent neutralization by pentameric DH1017.IgM mAb depends on isotype DH1017.IgM can engage all binding sites concurrently through different angles of approach DH1017.IgM protects mice against lethal ZIKV challenge

Background: Network propagation has been widely used for nearly 20 years to predict gene functions and phenotypes. Despite the popularity of this approach, little attention has been paid to the question of provenance tracing in this context, e.g., determining how much any experimental observation in the input contributes to the score of every prediction. Results: We design a network propagation framework with two novel components and apply it to predict human proteins that directly or indirectly interact with SARS-CoV-2 proteins. First, we trace the provenance of each prediction to its experimentally validated sources, which in our case are human proteins experimentally determined to interact with viral proteins. Second, we design a technique that helps to reduce the manual adjustment of parameters by users. We find that for every top-ranking prediction, the highest contribution to its score arises from a direct neighbor in a human protein-protein interaction network. We further analyze these results to develop functional insights on SARS-CoV-2 that expand on known biology such as the connection between endoplasmic reticulum stress, HSPA5, and anti-clotting agents. Conclusions: We examine how our provenance tracing method can be generalized to a broad class of network-based algorithms. We provide a useful resource for the SARS-CoV-2 community that implicates many previously undocumented proteins with putative functional relationships to viral infection. This resource includes potential drugs that can be opportunistically repositioned to target these proteins. We also discuss how our overall framework can be extended to other, newly-emerging viruses.

Zika virus (ZIKV) is an emerging flavivirus of global concern. ZIKV infection of the central nervous system has been linked to a variety of clinical syndromes, including microcephaly in fetuses and rare but serious neurologic disease in adults. However, the potential for ZIKV to influence brain physiology and host behavior following recovery from apparently mild or subclinical infection is less well understood. Furthermore, though deficits in cognitive function are well-documented following recovery from neuroinvasive viral infection, the potential impact of ZIKV on other host behavioral domains has not been thoroughly explored. In our study, we performed transcriptomic profiling of primary neuron cultures following ZIKV infection, which revealed altered expression of key genes associated with major psychiatric disorders, such as bipolar disorder and schizophrenia. Gene ontology enrichment analysis also revealed significant changes in gene expression associated with fundamental neurobiological processes, including neuronal development, neurotransmission, and others. These alterations to neurologic gene expression were also observed in the brain in vivo using an immunocompetent mouse model of ZIKV infection. Mechanistic studies identified TNF-α signaling via TNFR1 as a major regulatory mechanism controlling ZIKV-induced changes to neurologic gene expression. Our studies reveal that cell-intrinsic innate immune responses to ZIKV infection profoundly shape neuronal transcriptional profiles, highlighting the need to further explore associations between ZIKV infection and disordered host behavioral states.

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ∼50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine ( Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19 ) and cytokine ( Ifn-λ and Tnf-α ) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. Importance Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

The coronavirus disease 2019 (COVID-19) has been ravaging throughout the world for more than two years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the viral RNA-dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Here, we reveal that RdRp can recognize and utilize nucleoside diphosphates (NDPs) as a substrate to synthesize RNAs with an efficiency of about two thirds of using nucleoside triphosphates (NTPs) as a substrate. NDPs incorporation is also template-specific and has high fidelity. Moreover, RdRp can incorporate β-d-N4-hydroxycytidine (NHC) into RNA while using diphosphate form molnupiravir (MDP) as a substrate. We also observed that MDP is a better substrate for RdRp than the triphosphate form molnupiravir (MTP).

Recently, the association prediction between viruses and drugs has drawn more and more attention. A growing number of studies have shown that the problem of antiviral drug resistance is increasing and has become a major problem plaguing the medical community. Moreover, the development cycle of new drugs is long and requires a lot of funds. If new viruses emerge, effective antiviral drugs are urgently needed. Therefore, effective calculation methods are required to predict potential antiviral drugs. In this paper, we developed a computational model of Matrix Decomposition and Heterogeneous Graph based Inference for Drug-Virus Association (MDHGIVDA) to predict potential drug-virus associations. MDHGIVDA integrated virus sequence similarity, drug chemical structure similarity, drug side effect similarity, Gaussian interaction profile kernel similarity for drugs and viruses, new drug-virus associations matrix obtained by matrix decomposition to discover new drug-virus associations. Due to the use of matrix factorization and heterogeneous graphs, our model has a high prediction accuracy compared with the previous four models. In the global and local leave-one-out cross validation (LOOCV), MDHGIVDA obtained area under the receiver operating characteristics curve (AUC) of 0.8528 and AUC of 0.8532, respectively. In addition, in the five-fold cross validation, the AUC and the standard deviation is 0.8299 0.0037, which shows that MDHGIVDA has stability and high prediction accuracy. In the case studies of three important viruses, 18, 14, and 16 out of the top 20 predicted drugs for Zika virus (ZIKV), Severe Acute Respiratory Syndrome Coronavirus 2 ( SARS-COV-2 ), Human Immunodeficiency Virus-1 (HIV-1) were verified respectively by searching the literature on PubMed. These results showed that MDHGIVDA is effective in predicting potential drug-virus associations.

Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed that in utero infection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline. Summary Statement Zika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

Background: COVID-19 is an infectious disease caused by the new coronavirus, and its widespread epidemic has caused many deaths and health, social, and economic consequences in the world. The purpose of this study was to explain self-care behaviors against COVID-19 based on the health belief model (HBM) in pregnant women. Method The present study was conducted using a descriptive-analytical approach with the participation of 230 pregnant women referred to health centers in Urmia in 2021. The participants were selected using multi-stage random sampling. The data were collected using a valid and reliable questionnaire including participants’ demographic characteristics, the HBM items, and items relating to self-care behaviors against COVID-19. The data were analyzed using descriptive and inferential statistical methods (frequency, mean, standard deviation, Pearson correlation coefficient, and linear regression) in SPSS software (version 25). Results The results of this study showed that the rate of self-care behaviors against COVID-19 in the pregnant women participating in the present study was not very favorable. It was also shown that among the constructs of the HBM, awareness, self-efficacy, perceived barriers, and perceived severity were the most important predictors of self-care behaviors with a variance of 24% change among the pregnant women. Conclusion Awareness, self-efficacy, perceived barriers, and perceived severity were found in this study as the strongest predictors of self-care behaviors among pregnant women. The results of the study can be useful in planning educational and behavioral interventions to increase the adoption of self-care behaviors against COVID-19 and institutionalize health-promoting behaviors in women.

The C30 Endopeptidase (3C-like protease; 3CL pro ) is essential for the life cycle of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) since it plays a pivotal role in viral replication and transcription and is hence a promising drug target. Molecules isolated from animals, insects, plants or microorganisms can serve as a scaffold for the design of novel biopharmaceutical products. Crotamine, a small cationic peptide from the venom of the rattlesnake Crotalus durissus terrificus has been the focus of many studies since it exhibits activities such as analgesic, in vitro antibacterial and hemolytic activities. The crotamine derivative L-peptides (L-CDP) that inhibit the 3CL protease in the low µM range were examined since they are susceptible to proteolytic degradation; we explored the utility of their D-enantiomers form. Comparative uptake inhibition analysis showed D-CDP as a promising prototype for a D-peptide-based drug. We also found that the D-peptides can impair SARS-CoV-2 replication in vivo , probably targeting the viral protease 3CL pro .

SUMMARY Variation in the human genome contributes to abundant diversity in human traits and vulnerabilities, but the underlying molecular and cellular mechanisms are not yet known, and will need scalable approaches to accelerate their recognition. Here, we advanced and applied an experimental platform that analyzes genetic, molecular, and phenotypic heterogeneity across cells from very many human donors cultured in a single, shared in vitro environment, with algorithms (Dropulation and Census-seq) for assigning phenotypes to individual donors. We used natural genetic variation and synthetic (CRISPR-Cas9) genetic perturbations to analyze the vulnerability of neural progenitor cells to infection with Zika virus. These analyses identified a common variant in the antiviral IFITM3 gene that regulated IFITM3 expression and explained most inter-individual variation in NPCs’ susceptibility to Zika virus infectivity. These and other approaches could provide scalable ways to recognize the impact of genes and genetic variation on cellular phenotypes. HIGHLIGHTS Measuring cellular phenotypes in iPSCs and hPSC-derived NPCs from many donors Effects of donor sex, cell source, genetic and other variables on hPSC RNA expression Natural genetic variation and synthetic perturbation screens both identify IFITM3 in NPC susceptibility to Zika virus A common genetic variant in IFITM3 explains most inter-individual variation in NPC susceptibility to Zika virus

Background Many low-and middle-income country (LMIC) researchers have disadvantages when applying for research grants. Crowdfunding may help LMIC researchers to fund their research. Crowdfunding organizes large groups of people to make small contributions to support a research study. This manuscript synthesizes global qualitative evidence and describes a TDR crowdfunding pilot for LMIC-based researchers. Methods Our global systematic review and qualitative evidence synthesis searched six databases for qualitative data. We used a thematic synthesis approach and assessed our findings using the GRADE-CERQual approach. Building on the review findings, we organized a crowdfunding pilot to support LMIC researchers and use crowdfunding. The pilot provided an opportunity to assess the feasibility of crowdfunding for infectious diseases of poverty research in resource-constrained settings. Results Nine studies were included in the qualitative evidence synthesis and we identified seven themes. Seven studies demonstrated that strong public engagement facilitated crowdfunding for research. Other themes included the correlates of crowdfunding success, risks of crowdfunding, and risk mitigation strategies. Our pilot data suggest that crowdfunding is feasible in diverse LMIC settings. Three researchers launched crowdfunding campaigns, met their goals and received substantial monetary (raising a total of $26,546 across all five campaigns) and non-monetary contributions. Two researchers are still preparing for campaign launch due to COVID-19 related difficulties. Conclusion Public engagement provides a foundation for effective crowdfunding for health research. Our evidence synthesis and pilot data provide practical strategies for LMIC researchers to engage the public and use crowdfunding. A practical guide was created alongside to facilitate these activities across multiple settings. What is already known? Crowdfunding has been used to fund health causes, technology start-ups, creative projects, and more recently, scientific research. Although crowdfunding has been used for research funding in high-income settings, there is less evidence from LMIC settings. In addition, previous reviews of crowdfunding have not focused on public engagement strategies that may be important for developing effective crowdfunding campaigns. What are the new findings? - Our qualitative evidence synthesis finds that crowdfunding research focuses on creators and backers in high-income settings, neglecting LMIC researchers. - The TDR pilot programme suggests that crowdfunding is feasible for LMIC researchers. Three of the five pilot finalists exceeded their crowdfunding goals and received substantial non-monetary contributions.

ABSTRACT Point-of-care testing (POCT) offers several advantages over conventional laboratory testing. Nonetheless, a faster turnaround time, with less invasive procedures, is not enough if not associated with an acceptable level of accuracy. Here, we show the analytical validation behind the Hilab Flow (HiF), a multi-analyte POCT analyzer. HiF quantitative and qualitative tests for 6,175 clinical samples were compared to gold-standard methods from College of American Pathologists accredited laboratories. The compatibility between methods was evaluated in terms of association and clinical agreement. The established approval criteria was a kappa agreement > 0.8. A strong concordance was observed for the 27 analytes tested. Accuracy was greater than 90% for all HiF exams, indicating a good clinical agreement to gold standard laboratory testing. Results indicate that all quantitative and qualitative tests are suitable for POCT and present a reliable performance. HiF stands as a useful tool to aid decision-making in the clinical setting, with potential to contribute to healthcare solutions in diagnostic medicine worldwide.

One of the most important strategies for mitigation and managing pandemics is widespread, rapid and inexpensive testing and isolation of infected patients. In this study, we demonstrate large area, label-free, and rapid testing sensor platforms fabricated on both rigid and flexible substrates for fast and accurate detection of SARS-CoV-2. SERS enhancing metal insulator metal (MIM) nanostructures are modeled using finite element simulations and then fabricated using nanoimprint lithography (NIL) and transfer printing. The SERS signal of various viral samples, including spiked saliva, was analyzed using machine learning classifiers. We observe that our approach can obtain the test results typically within 25 minutes with a detection accuracy of at least 83% for the viral samples. We envision that this approach which features large area nanopatterning, fabrication in both rigid and flexible formats for wearables, SERS spectroscopy and machine learning can enable new types of rapid, label-free biosensors for screening pathogens and managing current and future pandemics.

The methanolic extract of the fungus Lentinus crinitus was submitted to biological assays, identification of the chemical composition by LC-MS, and in silico study by molecular docking with all identified compounds. The test against Artemis salina reached LD 50 > 1000 μg/mL within 24h, and total mortality within 48 hours; the antioxidant test 62.4% inhibition in 1.0 mg/mL was obtained. Only 16 compounds were identified from the LC-MS analysis based on the comparison of reports already recorded in the literature. Most of the compounds identified here are described for the first time in the genus Lentinus . These results showed that the fungus is a producer of different classes of secondary metabolites biologically active. The results of the molecular docking simulation of the identified phytochemicals presented 1,13,4-di-O-Caffeoylquinic, as the leading promising candidate in the inhibition of the Zika virus.

Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) protein, mRNA, and miRNA cargo, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.

ABSTRACT Introduction Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurological side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4000 ZIKV cases. Whether the neurological symptoms of ZIKV infection are a consequence of autoimmunity or direct neurotoxicity is unclear. Methods We employed rat dorsal root ganglion (DRG) neurons, Schwann cells (SCs), and human stem cell-derived sensory neurons myelinated with rat SCs as cellular models to screen for IgG and IgM autoantibodies reactive to peripheral nerve in sera of ZIKV patients with and without GBS. In this study, 52 ZIKV-GBS patients were compared with 134 ZIKV-infected patients, and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. Results Overall, IgG antibody reactivity to rat SCs (6.5%) and myelinated co-cultures (9.6%) were significantly higher, albeit infrequently, in the ZIKV-GBS group compared to all controls. IgM antibody immunoreactivity to DRGs (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared to other controls, while IgM reactivity to co-cultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from one patient were confirmed to react with neurofascin-155 and 186. Serum from a ZIKV non-GBS patient displayed strong myelin-binding and anti-lipid antigen reaction characteristics. There was no significant association of ZIKV-GBS with any anti-glycolipid antibodies. Conclusion Autoantibodies in ZIKV associated GBS patients’ sera target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.

We study the effects of firm-level exposure to an epidemic disease on corporate cash holdings amongst U.S firms. Using a text-based measure of firm-level exposure to epidemic diseases and difference-in-difference estimation strategy, we document a positive relationship between the onset of an epidemic disease and corporate cash holdings. We find that, amongst all the recent epidemics, COVID-19 has the strongest impact on cash holdings and that this effect is mostly driven by negative sentiments around the COVID-19 pandemic.

Microcephaly has been regarded the most remarkable consequence of the Zika virus (ZIKV) epidemic in Brazil 2015. It remains to be determined whether there are factors that contribute to the degree of brain lesion associated with ZIKV infection during pregnancy. Previous studies showed that socioeconomic conditions correlate with ZIKV-associated microcephaly. Certain nutritional deficits display the potential to interfere in the mechanistic target of rapamycin (mTOR) signaling, which plays a major role in the pathophysiology of ZIKV-associated microcephaly. We hypothesize that a nutritional or environmental co-factor that interferes in mTOR signaling correlates with ZIKV-associated birth defects. To assess this hypothesis, we plan to: 1) develop a mouse model of ZIKV-associated microcephaly through intravenous injection of ZIKV and rapamycin for a straightforward interference on mTOR receptor; 2) determine in the experimental model and in cases of ZIKV-associated microcephaly the epigenetic signature (DNA methylation pattern) in neurons and muscle cells harvested by biopsy, and in hematopoietic and mesenchymal stem cells sorted from blood; 3) analyze through mass spectrometry in serum of pregnant female mice submitted to ZIKV and rapamycin injection and in serum of mothers of children with ZIKV-associated microcephaly the metabolomic pattern of cholesterol (a nutritional status marker), vitamin A and its metabolite retinoic acid, folate, and other metabolites related to these three nutritional factors; 4) check whether pregnant female mice submitted to intravenous injection of ZIKV and feed with a deficient diet of the most likely co-factor found in this study give birth to microcephalic mice with features that mimic clinical cases. In summary, our general objective is to develop an experimental model that mimics ZIKV-associated microcephaly cases and to find a co-factor involved in the microcephaly outbreak in Brazil 2015.