Results 751-775 of about 1,000
  1. AUTHOR SUMMARY Phosphatidylserine (PS) receptors are PS binding proteins that mediate uptake of apoptotic bodies. Many enveloped viruses utilize this PS/PS receptor mechanism to adhere to and internalize into the endosomal compartment of cells and this is termed apoptotic mimicry. For viruses that have a mechanism(s) of endosomal escape, apoptotic mimicry is a productive route of virus entry. We evaluated if PS receptors serve as cell surface receptors for SARS-CoV-2 and found that the PS receptors, AXL, TIM-1 and TIM-4, facilitated virus infection when low concentrations of the SARS-CoV-2 cognate receptor, ACE2, was present. Consistent with the established mechanism of PS receptor utilization by other viruses, PS liposomes competed with SARS-CoV-2 for binding and entry. We demonstrated that this PS receptor enhances SARS-CoV-2 binding to and infection of an array of human lung cell lines and is an under-appreciated but potentially important host factor facilitating SARS-CoV-2 entry.
    Date: 2021-06-15
    Authors: Bohan D, Van Ert H, Ruggio N, Rogers KJ, Badreddine M, Aguilar Briseño JA, Chavez RAR, Gao B, Stokowy T, Christakou E, Micklem D, Gausdal G, Haim H, Minna J, Lorens JB, Maury W.
    Ref: bioRxiv
  2. Background: Neurological manifestation and complications are common due to the coronavirus infectious disease COVID-19. It affects higher functions, cranial nerves and the motor system. It can lead to headaches, convulsions, mental and psychological changes like delirium and insomnia. Guillain Barre syndrome rarely occurs as a consequence of or in co-incidence with COVID-19. The authors report a case of Guillain Barre syndrome as an example of a success story in managing a complicated case of COVID-19 in an elderly male with signs of a poor prognosis. Case presentation: A previously healthy 70-year-old man presented (on the 25th of June, 2020) with a fever and cough followed by quadriplegia and facial weakness one week later. He tested positive for COVID-19, and a nerve conduction study revealed demyelinating neuropathy consistent with Guillain Barre syndrome. He received treatment in the form of intravenous immunoglobulin with marked improvement despite poor prognostic features. Conclusion: Patients with COVID-19 can present with any symptoms, including diseases of the nervous system and peripheral nerves such as Guillain Barre syndrome, which respond very well to IVIG treatment despite poor prognostic factors such as old age, gender, rapid onset of complete paralysis, lymphopenia and a ground-glass appearance on CT chest scans, which all existed in this case.
    Date: 2021-06-14
    Authors: Ibrahim EAA, Ahmed KAHM, Salah ET.
    Ref: Research Square
  3. Background The COVID-19 pandemic generated a growing interest in and need for evidence-based tools to facilitate the implementation of emergency management strategies within public health practice. Quality improvement (QI) has been identified as a key framework and philosophy to guide organizational emergency response efforts; however, the nature and extent to which it has been used in public health settings during the COVID-19 pandemic remains unclear. Methods We conducted a scoping review of literature published January 2020 – February 2021 and focused on the topic of QI at public health agencies during the COVID-19 pandemic. The search was conducted on four bibliographic databases, in addition to a supplementary grey literature search using custom Google search engines and targeted website search methods. Of the 1,878 peer-reviewed articles assessed, 15 records met the inclusion criteria. An additional 11 relevant records were identified during the grey literature search, for a total of 26 records included in the scoping review. Results Records were organized into five topics: 1) collaborative problem solving and analysis with stakeholders; 2) supporting learning and capacity building in QI; 3) learning from past emergencies; 4) implementing QI methods during COVID-19; and 5) evaluating performance using frameworks/indicators. Conclusions The literature indicates that QI-oriented activities are occurring at the organizational and program levels to enhance COVID-19 response. To optimize the benefits that QI approaches and methodologies may offer, it is important for public health agencies to focus on both widespread integration of QI as part of an organization’s management philosophy and culture, as well as project level activities at all stages of the emergency management cycle.
    Date: 2021-06-12
    Authors: Yin XC, Pang M, Law M, Guerra F, O’Sullivan T, Laxer RE, Schwartz B, Khan Y.
    Ref: medRxiv
  4. T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 as well as influenza A virus. Tfh-independent responses were mediated by a population we call lymph node (LN)-Th1 cells, which remain in the LN and interact with B cells outside of GCs to promote high-affinity but broad-spectrum antibodies. Strikingly, antibodies generated in the presence and absence of Tfh cells displayed similar neutralization potency against homologous SARS-CoV-2 as well as the B.1.351 variant of concern. These data support a new paradigm for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GCs and even compensate for GCs damaged by viral inflammation. One-Sentence Summary Complementary pathways of antibody production mediate neutralizing responses to SARS-CoV-2.
    Date: 2021-06-11
    Authors: Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC.
    Ref: bioRxiv
  5. The Aedes aegypti mosquito is a vector of several diseases, such as dengue, malaria and the Zika virus. Synthetic insecticides such as chlorpyrifos and chlorothalonil have been used for plague control, despite causing damage to the environment and to humans. It is therefore important to study natural active compounds with a low environmental impact. The present paper developed an environmentally friendly formulation of silk fibroin (SF) associated with fatty acid esters [ethyl (FAEE-SF), propyl (FAPE-SF) and butyl (FABE-SF)] from Astrocaryum murumuru Mart. fat, which was effective against Aedes aegypti 3th instar larvae. The FABE-SF nanoemulsion induced a higher mortality rate in the larvae of the A. aegypti after 48 h (LC 50  = 18.92 µg / mL). The stabilities of the nanoemulsions were monitored for 21 days, and FABE-SF exhibited greater stability throughout the monitored period, with average particle, zeta and PDI values of around 217 ± 0.85 nm, -25.6 ± 3.24 mV and 0.338 ± 0.01, respectively. This paper reported the first effective action of fatty acid esters from A. murumuru Mart. associated with silk fibroin against A. aegypti . The FABE-SF solution also had a low hemolytic index, suggesting that treatment may be safe for animal and human use.
    Date: 2021-06-11
    Authors: Marinho VHS, Neves FB, Jimenez DEQ, Oliveira FR, Santos AVTLT, Ferreira RMA, Souto RNP, Carvalho JCT, Yoshioka SA, Ferreira IM.
    Ref: Research Square
  6. No studies to date allow us to explain the dynamics of science and research behavior in the presence of crisis to support research policy for allocating resources with effectiveness and planning scientific research to provide solutions directed to positive societal impact. The main goal of this study is to explain the research behavior and dynamics of science during a global crisis, focusing on Coronavirus Disease 2019 (COVID-19) that has generated a pandemic crisis worldwide. Results suggest critical characteristics of the research behavior and dynamics of science in global crisis, namely: evolution of research field is driven by new and consequential environmental threats in human society to be solved in a short run; evolution of crisis-driven research fields field is pulled by few (parent) disciplines (3–5) that generate more than 80% of documents; the most active institutions in crisis-driven studies are mainly academic institutions localized in advanced countries; main funding institutions in scientific production of crisis-driven research fields are public organizations of rich nations and global charitable foundations; the most productive countries of crisis-driven research fields are nations direct to support their global leadership; moreover, research behavior of crisis-driven research fields is mainly based on scientific publications having open access for a widespread diffusion of results for a higher social impact; finally, scientific production of crisis-driven research field has a higher density of short communications with letters and notes to systematize quickly findings, publish and spread them. Overall, then, this study provides critical characteristics of research behavior and dynamics of science in global crises that could be of benefit to policymakers to design science policies and plan research programmes to generate fruitful science advances and technological breakthroughs directed to reduce negative effects of crisis on socioeconomic systems and improve wellbeing of people.
    Date: 2021-06-11
    Authors: Coccia M.
    Ref: Research Square
  7. Liquid-liquid phase separation is prone to occur when positively charged proteins interact with nucleic acids. Here, we studied biophysical properties of Dengue (DENV) and Zika (ZIKV) virus capsid proteins to understand the process of RNA genome encapsidation. In this route, the capsid proteins efficiently recruit the viral RNA at the ER membrane to yield nascent viral particles. However, little is known either about the molecular mechanisms by which multiple copies of capsid proteins assemble into nucleocapsids or how the nucleocapsid is recruited and wrapped by the ER membrane during particle morphogenesis. Here, we measured relevant interactions concerning the viral process using purified DENV and ZIKV capsids proteins, membranes mimicking the ER lipid composition and nucleic acids at in vitro conditions. We found that both ZIKV and DENV capsid proteins bound to liposomes at liquid-disordered phase regions and docked exogenous membranes and RNA molecules. When the proteins bound nucleic acids, droplet liquid-liquid phase separation was observed. We characterized these liquid condensates by measuring nucleic acid partition constant and the extent of water dipolar relaxation observing a cooperative process for the formation of the new phase that involves a distinct water organization. Our data supports a new model in which capsid-RNA complexes directly bind the ER membrane, seeding the process of RNA recruitment for viral particle assembly. These results contribute to understand the viral nucleocapsid formation as a stable liquid-liquid phase transition, which could be relevant for Dengue and Zika gemmation, opening new avenues for antiviral intervention.
    Date: 2021-06-10
    Authors: Ambroggio EE, Navarro GSC, Socas LBP, Bagatolli LA, Gamarnik AV.
    Ref: bioRxiv
  8. Zika virus is a mosquito-borne flavivirus known to cause severe birth defects and neuroimmunological disorders. We have previously demonstrated that mosquito transmission of Zika virus decreases with temperature. While transmission was optimized at 29°C, it was limited at cool temperatures (< 22°C) due to poor virus establishment in the mosquitoes. Temperature is one of the strongest drivers of vector-borne disease transmission due to its profound effect on ectothermic mosquito vectors, viruses, and their interaction. Although there is substantial evidence of temperature effects on arbovirus replication and dissemination inside mosquitoes, little is known about whether temperature affects virus replication directly or indirectly through mosquito physiology. In order to determine the mechanisms behind temperature-induced changes in Zika virus transmission potential, we investigated different steps of the virus replication cycle in mosquito cells (C6/36) at optimal (28°C) and cool (20°C) temperatures. We found that cool temperature did not alter Zika virus entry or translation but reduced the amount of double-stranded RNA replication intermediates. If replication complexes were first formed at 28°C and the cells were subsequently shifted to 20°C, the late steps in the virus replication cycle were efficiently completed. These data suggest that cool temperature decreases the efficiency of Zika virus genome replication in mosquito cells. This phenotype was observed in the Asian-lineage of Zika virus, while the African-lineage Zika virus was less restrictive at 20°C. Importance With half of the human population at risk, arboviral diseases represent a substantial global health burden. Zika virus, previously known to cause sporadic infections in humans, emerged in the Americas in 2015 and quickly spread worldwide. There was an urgent need to better understand the disease pathogenesis, develop therapeutics and vaccines, as well as to understand, predict, and control virus transmission. In order to efficiently predict the seasonality and geography for Zika virus transmission, we need a deeper understanding of the host-pathogen interactions and how they can be altered by environmental factors such as temperature. Identifying the step in the virus replication cycle that is inhibited in cool conditions can have implications in modeling the temperature suitability for arbovirus transmission as global environmental patterns change. Understanding the link between pathogen replication and environmental conditions can potentially be exploited to develop new vector control strategies in the future.
    Date: 2021-06-08
    Authors: Tesla B, Powers JS, Barnes Y, Lakhani S, Acciani MD, Murdock CC, Brindley MA.
    Ref: bioRxiv
  9. Esta pesquisa analisou associações entre metapreocupações e sintomatologias ansiosa e depressiva no início da pandemia de COVID-19 no Brasil. Participaram do estudo 2.042 indivíduos, com idades entre 18-78 anos. Um questionário sociodemográfico, o 4-item Patient Health Questionnaire e o Meta-Worry Questionnaire foram respondidos online. Quatro modelos de Regressão Logística foram utilizados para estimar o efeito das variáveis independentes sobre as sintomatologias ansiosa e depressiva. As variáveis ser mais jovem, não ter renda fixa, perceber-se doente e exibir alto nível de metapreocupações ampliaram as chances de sintomas ansiosos e/ou depressivos. Concluiu-se que prover cuidado frente ao sofrimento psicológico é fundamental no combate à COVID-19, pois foram detectados fatores de suscetibilidade ao desenvolvimento de transtornos mentais no começo da pandemia no Brasil.
    Date: 2021-06-07
    Authors: Faro A, Silva-Santos L, Silva MC, Vasconcelos MM.
    Ref: SciELO Preprints
  10. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen leading to serious multi-organ damage. However, little is known about SARS-CoV-2-induced cellular alterations for understanding robust virus propagation yet. Here we report that SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics and activates epidermal growth factor receptor (EGFR)-mediated cell survival signal cascade for sustaining persistence of SARS-CoV-2. We found that SARS-CoV-2 causes increase in mitochondrial transmembrane potential by SARS-CoV-2 RNA-nucleocapsid cluster, thereby abnormally promoting mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) process followed by abundant ATP production. SARS-CoV-2 also activated EGFR signal cascade and subsequent mitochondrial EGFR accumulation which contributes to the maintenance of abnormal OXPHOS and viral propagation. Therapeutic options for the treatment of COVID-19 are still inadequate. The FDA-approved EGFR inhibitors caused a remarkable reduction in SARS-CoV-2 propagation. Among EGFR inhibitors, vandetanib showing the highest anti-SARS-CoV-2 efficacy exhibited the potent antiviral activity against various SARS-CoV-2 variants including B.1.1.7 (UK variant) and B.1.351 (SA variant) lineages in both in vitro cell culture and in vivo animal experiments using wild-type aged mouse susceptible to SARS-CoV-2 infection, suggesting that EGFR is an attractive host target for combatting COVID-19. Overall, our results suggest that SARS-CoV-2 induces aberrant mitochondrial dynamics and bioenergetics, which significantly contributes to robust SARS-CoV-2 propagation.
    Date: 2021-06-07
    Authors: Shin HJ, Ku KB, Yoon GY, Moon H, Kim C, Kim B, Oh J, Siddiqui A, Kim S.
    Ref: Research Square
  11. The emergence and re-emergence of RNA virus outbreaks highlight the urgent need for the development of broad-spectrum antiviral agents. Arthrospira maxima has be used as a food source for a long time, and the protein or polysaccharide fractions were evidenced to have antiviral activity, therefore we examined the antiviral efficacy of hot water extract from Arthrospira maxima (AHWE), on Enterovirus 71 (EV71), Influenza virus, Herpes simplex virus (HSV), Respiratory syncytial virus (RSV), Ebola virus, and Coronavirus for antiviral spray application. In this study, we demonstrated that the AHWE shown 90 to 100% inhibition rate on the plaque formation of EV71, HSV-1, HSV-2, influenza virus, RSV, 229E and SARS-COV2 at virus attachment stage, and the long-lasting protection study also found while the AHWE was pre-exposed to the open air for more than 4 hours in plaque reduction assay. In addition, AHWE also had inhibitory effect on Ebola virus replication at 500 ug/ml. Finally, AHWE also shown no toxicity and skin sensitivity that imply it could be safe for future clinical use if approved by FDA. In conclusion, this study suggests that AHWE could be developed as a potential broad-spectrum antivirus spray product and therapeutic agent.
    Date: 2021-06-07
    Authors: Chen Y, Liao Y, Huang J, Kung Y, Chiueh C.
    Ref: bioRxiv
  12. Hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma (CP) are under evaluation in several clinical trials of hospitalized COVID-19 patients. Here we explored the antibody epitope repertoire, antibody binding and virus neutralizing capacity of six hCoV-2IG batches as well as nine convalescent plasma (CP) lots against SARS-CoV-2 and emerging variants of concern (VOC). The Gene-Fragment Phage display library spanning the SARS-CoV-2 spike-based epitope-mapping demonstrated broad recognition of multiple antigenic sites spanning the entire spike including NTD, RBD, S1/S2 cleavage site, S2-fusion peptide and S2-heptad repeat regions. Antibody binding to the immunodominant epitopes was higher for hCoV-2IG than CP, with predominant binding to the fusion peptide. In the pseudovirus neutralization assay (PsVNA) and in the wild-type SARS-CoV-2 PRNT assay, hCoV-2IG lots showed higher titers against the WA-1 strain compared with CP. Neutralization of SARS-CoV-2 VOCs from around the globe were reduced to a different extent by hCoV-2IG lots. The most significant loss of neutralizing activity was seen against the B.1.351 (9-fold) followed by P.1 (3.5-fold), with minimal loss of activity against the B.1.17 and B.1.429 ( < 2-fold). Again, the CP showed more pronounced loss of cross-neutralization against the VOCs compared with hCoV-2IG. Significant reduction of hCoV-2IG binding was observed to the RBD-E484K followed by RBD-N501Y and minimal loss of binding to RBD-K417N compared with unmutated RBD. This study suggests that post-exposure treatment with hCoV-2IG is preferable to CP. In countries with co-circulating SARS-CoV-2 variants, identifying the infecting virus strain could inform optimal treatments, but would likely require administration of higher doses achieved by larger volumes or repeated infusions of hCOV-2IG or CP, in patients infected with the emerging SARS-CoV-2 variants. Funding: The research work described in this manuscript was supported by FDA Medical Countermeasures Initiative (MCMi) grant # OCET 2021-1565 and NIH-NIAID IAA #AAI20040. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interest: The authors declare no competing interests. Ethical Approval: This study was approved by Food and Drug Administration’s Research Involving Human Subjects Committee (RIHSC #2020-04-02). This study complied with all relevant ethical regulations for work with human participants, and informed consent was obtained. Samples were collected from patients who provided informed consent to participate in the study.
    Date: 2021-06-02
    Authors: Tang J, Lee Y, Ravichandran S, Grubbs G, Huang C, Stauft CB, Wang TT, Golding B, Golding H, Khurana S.
    Ref: SSRN
  13. The COVID-19 pandemics unfolded due to the widespread SARS-CoV-2 transmission reinforced the urgent need for affordable molecular diagnostic alternative methods for massive testing screening. We present the clinical validation of a pH-dependent colorimetric RT-LAMP (reverse transcription loop-mediated isothermal amplification) for SARS-CoV-2 detection. The method revealed a limit of detection of 19.3 ± 2.7 viral genomic copies/μL when using RNA extracted samples obtained from nasopharyngeal swabs collected in guanidine-containing viral transport medium. Typical RT-LAMP reactions were performed at 65 ºC for 30 min. When compared to RT-qPCR, up to Ct value 32, RT-LAMP presented 97% (87.4-99.4% 95% CI) sensitivity and 100% (86.2-100%) specificity for SARS-CoV-2 RNA detection targeting N gene. No cross-reactivity was detected when testing other non-SARS-CoV virus, confirming high specificity. The test is compatible with primary RNA extraction free samples. We also demonstrated that colorimetric RT-LAMP can detect SARS-CoV-2 variants of concern (VOC) and variants of interest (VOI), such as variants occurring in Brazil named P.1, P.2, B.1.1.374 and B.1.1.371. The method meets point-of-care requirements and can be deployed in the field for high-throughput COVID-19 testing campaigns, especially in countries where COVID-19 testing efforts are far from ideal to tackle the pandemics. Although RT-qPCR is considered the gold standard for SARS-CoV-2 RNA detection, it requires expensive equipments, infrastructure and highly trained personnel. In contrast, RT-LAMP emerges as an affordable, inexpensive and simple alternative for SARS-CoV-2 molecular detection that can be applied to massive COVID-19 testing campaigns and save lives.
    Date: 2021-06-02
    Authors: Alves PA, Oliveira dEG, Franco-Luiz APM, Almeida LT, Gonçalves AB, Borges IA, Rocha FdS, Rocha RP, Bezerra MF, Miranda P, Capanema FD, Martins HR, Weber G, Teixeira SMR, Wallau GL, do Monte-Neto RL.
    Ref: medRxiv
  14. Zika virus (ZIKV) is a mosquito-born flavivirus which human infection became relevant dur-ing recent outbreaks in Latin America, due to its unrecognized association with fetal neurologi-cal disorders. Currently there are no approved effective antivirals or vaccines for treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections, that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV refer-ence strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the later. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine a potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across fla-vivirus, susceptible to be blocked by modified more specific adamantane compounds.
    Date: 2021-06-01
    Authors: Arias-Arias JL, Vega-Aguilar F, Picado-Soto D, Corrales-Aguilar E, Loría GD.
    Ref: Preprints.org
  15. Summary The endomembrane reticulum (ER) is largely reorganized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 ORF3a and membrane (M) protein expression affects ER-derived structures including cubic membrane and double membrane vesicles in coronavirus-infected cells; however, the molecular mechanisms underlying ER remodeling remain unclear. We introduced a “plug and playable” proximity labeling tool (TurboID-GBP) for interactome mapping of GFP-tagged SARS-CoV-2 ORF3a and M proteins. Through mass spectrometric identification of the biotinylated lysine residue (K+226 Da) on the viral proteins using Spot-TurboID workflow, 117 and 191 proteins were robustly determined as ORF3a and M interactomes, respectively, and many, including RNF5 (E3 ubiquitin ligase), overlap with the mitochondrial-associated membrane (MAM) proteome. RNF5 expression was correlated to ORF3a ubiquitination. MAM formation and secreted proteome profiles were largely affected by ORF3a expression. Thus, SARS-CoV-2 may utilize MAM as a viral assembly site, suggesting novel anti-viral treatment strategies for blocking viral replication in host cells. Highlights SARS-CoV-2 proteins ORF3a and M alter endoplasmic reticulum proteome profile ORF3a affects mitochondrial-associated membrane formation SARS-CoV-2 may utilize mitochondrial-associated membrane as viral assembly site ORF3a and M interactome proteins may serve as targets for COVID-19 treatment eTOC Blurb ER remodelling by SARS-CoV-2 ORF3a and M protein
    Date: 2021-06-01
    Authors: Lee Y, Jung M, Kim J, Kang M, Kwak C, Kim J, Mun J, Rhee H.
    Ref: bioRxiv
  16. The impact of the ongoing COVID-19 pandemic is being felt in all spheres of our lives -- cutting across the boundaries of nation, wealth, religions or race. From the time of the first detection of infection among the public, the virus spread though almost all the countries in the world in a short period of time. With humans as the carrier of the virus, the spreading process necessarily depends on the their mobility after being infected. Not only in the primary spreading process, but also in the subsequent spreading of the mutant variants, human mobility plays a central role in the dynamics. Therefore, on one hand travel restrictions of varying degree were imposed and are still being imposed, by various countries both nationally and internationally. On the other hand, these restrictions have severe fall outs in businesses and livelihood in general. Therefore, it is an optimization process, exercised on a global scale, with multiple changing variables. Here we review the techniques and their effects on optimization or proposed optimizations of human mobility in different scales, carried out by data driven, machine learning and model approaches.
    Date: 2021-05-31
    Authors: Biswas S, Mandal AK.
    Ref: arXiv
  17. Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in an aggressive timeline. In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the SARS-CoV-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAb™ mouse model for increased diversity. The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation. By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.
    Date: 2021-05-31
    Authors: Mullen TE, Abdullah R, Boucher J, Brousseau AS, Dasuri NK, Ditto NT, Doucette AM, Emery C, Gabriel J, Greamo B, Patil KS, Rothenberger K, Stolte J, Souders CA.
    Ref: bioRxiv
  18. This survey analyses the role of data-driven methodologies for pandemic modelling and control. We provide a roadmap from the access to epidemiological data sources to the control of epidemic phenomena. We review the available methodologies and discuss the challenges in the development of data-driven strategies to combat the spreading of infectious diseases. Our aim is to bring together several different disciplines required to provide a holistic approach to epidemic analysis, such as data science, epidemiology, and systems-and-control theory. A 3M-analysis is presented, whose three pillars are: Monitoring, Modelling and Managing. The focus is on the potential of data-driven schemes to address three different challenges raised by a pandemic: (i) monitoring the epidemic evolution and assessing the effectiveness of the adopted countermeasures; (ii) modelling and forecasting the spread of the epidemic; (iii) making timely decisions to manage, mitigate and suppress the contagion. For each step of this roadmap, we review consolidated theoretical approaches (including data-driven methodologies that have been shown to be successful in other contexts) and discuss their application to past or present epidemics, such as Covid-19, as well as their potential application to future epidemics.
    Date: 2021-05-30
    Authors: Alamo T, Reina DG, Gata PM, Preciado VM, Giordano G.
    Ref: arXiv
  19. Although the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD-B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune “set-point.” Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies. One Sentence Summary Mass cytometry reveals acute ZIKV infection cellular immune signatures that predict high or low neutralizing antibody titers 6 months post-infection.
    Date: 2021-05-28
    Authors: McCarthy EE, Odorizzi PM, Lutz E, Smullin CP, Tenvooren I, Stone M, Simmons G, Hunt PW, Feeney ME, Norris PJ, Busch MP, Spitzer MH, Rutishauser RL.
    Ref: bioRxiv
  20. Background: In Europe, Ae. albopictus is an important vector of chikungunya virus, Dirofilaria nematodes and was involved in local autochthonous circulation of dengue virus and Zika virus. Due to the ongoing spread, a targeted field surveillance at potential points-of-entries for Aedes invasive mosquitoes was initiated for the Republic of Moldova in 2020 as part of the transboundary “Aedes Invasive Mosquito COST Action project”. MethodsIn 2020, ovitraps were positioned at each of three locations: the border crossing to Romania in Leuseni (Hancesti region), Chisinau International Airport and Chisinau Botanical Garden.ResultsA total of 188 Aedes spp. eggs were collected at the Chisinau International Airport between August and September 2020. Twenty-three adults reared in the laboratory were identified morphologically as Aedes albopictus (Skuse, 1895) and twelve selected specimens were confirmed by molecular barcoding of the cytochrome oxidase subunit I gene region. In addition, one adult female of Ae. albopictus was caught at the same site with a manual aspirator from a human.ConclusionsThis is the first documented report of Ae. albopictus in the Republic of Moldova. The presence of immature and adult stages indicates the local reproduction of the species in the country. Therefore, it is crucial to extend and strengthen surveillance of the invasive Aedes mosquitoes to prevent Ae. albopictus and other exotic mosquito species from establishing in the Republic of Moldova.
    Date: 2021-05-28
    Authors: Sulesco T, Busmachiu G, Lange U, Schmidt-Chanasit J, Lühken R.
    Ref: Research Square
  21. The unexpected outbreak of the new infectious disease called the novel coronavirus 2019 has a great impact on public health worldwide. The virus has challenged the healthcare systems globally, and it remains a mystery in front of them. Thus, there is a need to study how this deadly disease has been spread across the world in such a rapid phase. This study is beneficial to the industries that are affected by the current situation by making certain observations while considering the COVID-19 outbreak cases. It also helps these industries in taking the needed precautionary measures in the future if such a global pandemic situation arises. An interactive visual representation of this task efficiently and effectively done is more understandable and presentable. This study gives you a clear idea of COVID-19, Visual Analytics and its application in the field of public health, especially in the case of COVID-19. The main scope of this review is to create awareness among the community about the outbreak and spread of this contagious disease using the visual analytics approach.
    Date: 2021-05-26
    Authors: B LM, Joseph RB, Sunder R, Rajeswari M.
    Ref: SSRN
  22. Our atmosphere is constantly changing and new pathogens are erupting now and then and the existing pathogens are mutating continuously. Some of these pathogens, such as SARS-CoV-2, become so deadly that they put the whole technological advancement of healthcare under challenge. Within this very decade several other deadly virus outbreaks were witnessed by humans such as Zika virus, Ebola virus, MERS-coronavirus etc. Though conventional techniques have succeeded in detecting these viruses to some extent, these techniques are time-consuming, costly, and require trained human-resources. Plasmonic metamaterial-based biosensors might pave the way to low-cost rapid virus detection. So this review discusses in details the latest development in plasmonics and metamaterial-based biosensors for virus, viral particles and antigen detection and the future direction of research in this field. Emergence of quantum properties in biosensing, application of machine learning, artificial intelligence and novel materials in biosensing is also discussed in brief.
    Date: 2021-05-25
    Authors: Hassan MM, Sium FS, Islam F, Choudhury SM.
    Ref: arXiv
  23. Studies on the feeding behavior of hematophagous insects, particularly those of medical importance, are relevant for tracking possible pathogen transmission routes and identifying biases in the choice of vertebrates. We evaluated host selection of blood-feeding mosquitoes in a disturbed forest in the Magdalena Medio valley in Colombia from March 2017 to April 2018, after the introduction of Zika virus to the Americas from the 2015-2016 outbreak. We estimated vertebrate diversity and collected blood-engorged female mosquitoes. Mosquito genomic DNA/RNA was extracted for vertebrate host identification and pathogen detection. We performed conventional PCR and sequencing, using universal primers targeting vertebrate regions of the eukaryotic mitochondrial genome to determine bloodmeal host. Additionally, we tested for the presence of flaviviruses in all mosquito samples with RT-PCR. Based on the identity and quantity of detected bloodmeals, we performed mosquito-vertebrate interaction network analysis and estimated topology metrics. In total, we collected 292 engorged female mosquitoes representing 20 different species. Bloodmeal analyses identified 26 vertebrate species, the majority of which were mammals (N=16; 61.5%). No flavivirus infection was confirmed. Although feeding patterns varied, network analyses showed a high degree of specialization by mosquitoes and revealed ecological and phylogenetic relationships among the host community. We conclude that host selection or preference by mosquitoes is species specific.
    Date: 2021-05-25
    Authors: Hoyos J, Carrasquilla MC, Leon C, Montgomery JM, Salyer SJ, Komar N, González C.
    Ref: Research Square
  24. Starting February 2020, COVID-19 was confirmed in 11,946 people worldwide, with a mortality rate of almost 2%. A significant number of epidemic diseases including human Coronavirus display patterns. In this study with the benefit of data analytic, we develop regression models and a Susceptible-Infected-Recovered (SIR) model for the contagion to compare the performance of models to predict number of cases. first, we implement a good understanding of data and perform Exploratory Data Analysis (EDA). Then, we derive the parameters of the model from the available data corresponding to the top 4 regions based on the history of infections and the most infected people as of the end of August 2020. Then models are compared and further research are introduced.
    Date: 2021-05-25
    Authors: Abolmaali S.
    Ref: medRxiv
  25. Background: The emergence and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at late 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19). Although vaccines have been and are being developed, they are not accessible to everyone and not everyone can receive these vaccines. Also, it typically takes more than 10 years until a new therapeutic agent is approved for usage. Therefore, repurposing of known drugs can lend itself well as a key approach for significantly expediting the development of new therapies for COVID-19. Methods: We have been incorporated machine learning-based computational tools and in silico models into the drug discovery process to predict Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of 90 potential drugs for COVID-19 treatment identified from two independent studies mainly with the purpose of mitigating late-phase failures because of inferior pharmacokinetics and toxicity. Results: Here, summarized the cardiotoxicity and general toxicity profiles of 90 potential drugs for COVID-19 treatment and summarize the risks of repurposing and propose a stratification of patients accordingly. We shortlist a total of five compounds based on their non-toxic properties. Conclusion: In summary, this manuscript aims to provide a potentially useful source of essential knowledge on toxicity assessment of 90 compounds for health care practitioners and researchers to find off-label alternatives for the treatment for COVID-19. The majority of the molecules discussed in this manuscript have already moved into clinical trials and thus their known pharmacological and human safety profiles are expected to facilitate a fast track preclinical and clinical assessment for treating COVID-19.
    Date: 2021-05-21
    Authors: Aminpour M, Miranda-Delgado W, Wacker S, Noskov S, Houghton M, Tyrrell DL, Tuszynski JA.
    Ref: Research Square
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