Corpus overview


Overview

MeSH Disease

Human Phenotype

Pain (2)

Anxiety (1)

Falls (1)

Headache (1)

Ataxia (1)


Transmission

Seroprevalence
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    In silico identification and validation of inhibitors of the interaction between neuropilin receptor 1 and SARS-CoV-2 Spike MESHD protein

    Authors: Samantha Perez-Miller; Marcel Patek; Aubin Moutal; Carly R Cabel; Curtis A. Thorne; Samuel K Campos; Rajesh Khanna

    doi:10.1101/2020.09.22.308783 Date: 2020-09-23 Source: bioRxiv

    Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth MESHD and angiogenesis. In addition to a role in cancer MESHD, NRP-1 is a reported entry point for several viruses, including severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causal agent of coronavirus disease MESHD 2019 (COVID-19). The furin cleavage product of SARS-CoV-2 Spike MESHD protein takes advantage of the vascular endothelial growth factor A (VEGF-A) binding site on NRP-1 which accommodates a polybasic stretch ending in a C-terminal arginine. This site has long been a focus of drug discovery efforts for cancer MESHD therapeutics. We recently showed that interruption of the VEGF-A/NRP-1 signaling pathway ameliorates neuropathic pain MESHD pain HP and hypothesize that interference of this pathway by SARS-CoV-2 spike protein interferes with pain HP pain MESHD signaling. Here, we report hits from a small molecule and natural product screen of nearly 0.5 million compounds targeting the VEGF-A binding site on NRP-1. We identified nine chemical series with lead- or drug-like physico-chemical properties. Using an ELISA SERO, we demonstrate that six compounds disrupt VEGF-A-NRP-1 binding more effectively than EG00229, a known NRP-1 inhibitor. Secondary validation in cells revealed that almost all tested compounds inhibited VEGF-A triggered VEGFR2 phosphorylation. Two compounds displayed robust inhibition of a recombinant vesicular stomatitis MESHD stomatitis HP virus protein that utilizes the SARS-CoV-2 Spike for entry and fusion. These compounds represent a first step in a renewed effort to develop small molecule inhibitors of the VEGF-A/NRP-1 signaling for the treatment of neuropathic pain MESHD pain HP and cancer MESHD with the added potential of inhibiting SARS-CoV-2 virus entry.

    SARS-CoV-2 Spike MESHD protein hijacks VEGF-A/Neuropilin-1 receptor signaling to induce analgesia MESHD

    Authors: Aubin Moutal; Laurent F Martin; Lisa Boinon; Kimberly Gomez; Dongzhi Ran; Yuan Zhou; Harrison J Stratton; Cai Song; Shizhen Luo; Kerry Beth Gonzalez; Samantha Perez-Miller; Amol Patwardhan; Mohab Ibrahim; Rajesh Khanna

    doi:10.1101/2020.07.17.209288 Date: 2020-07-18 Source: bioRxiv

    Global spread of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2s Spike MESHD protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pronociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain MESHD pain HP model. A silencing of pain HP pain MESHD via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission TRANS in asymptomatic TRANS individuals. One Sentence SummarySARS-CoV-2s Spike protein promotes analgesia by interfering with VEGF-A/NRP1 pathway, which may affect disease transmission TRANS dynamics.

    The Psychological Effect of 2019 Coronavirus Disease MESHD Outbreak on Nurses Living in Islamic Culture Dominant Region, China

    Authors: Mengyao Jiang; Siyan Li; Dongli She; Fanghong Yan; Yuet Foon Chung; Lin Han

    doi:10.21203/rs.3.rs-18075/v1 Date: 2020-03-18 Source: ResearchSquare

    Background: The outbreak of Coronavirus Disease MESHD (COVID-19) in Wuhan, owing to the uncertain nature of COVID-19, can cause concerns about the potential health risks and may engender fear, anxiety HP anxiety MESHD, depression MESHD and so on. China is a multi-ethnic society, and Linxia Hui Autonomous MESHD Prefecture is a multi-ethnic residential city and is influenced profoundly by Islamic culture. Culture can influence perceptions, but it is unknown how much it affects frontline nurses’ perceptions of the emerging infectious disease MESHD outbreak. The aim of this study was to investigate the psychological characteristics of nurses with minority ethnic backgrounds in response to the public health crisis and to explore its related factors. Methods: We undertook a cross-sectional online survey in the Linxia Hui Autonomous MESHD Prefecture, Gansu province, China. There were eight secondary-level hospitals and one tertiary-level hospital, six of which were COVID-19-designated hospitals. The structured questionnaire consisted of demographic questionnaire, COVID-19 related questionnaire, Self-Rating Anxiety HP Anxiety MESHD Scale, and Self-rating Depression MESHD Scale. Results: A total of 1569 nurses enrolled in our online survey. The majority of the nurses were women (98.8%), aged TRANS younger than 40-year-old (90.3%), holders of a junior college degree (59.5%), married (74.6%), needed to care for children TRANS (63.9%) or elders (84.6%), with working years of less than 10 years (61.9%), and worked at non-high exposure departments(75%) in secondary hospital (66.9%) or COVID-19-designated hospital (85.4%). The anxiety HP anxiety MESHD and depression MESHD level (M± SD) were 42.56±8.95 and 46.52 ±11.883, respectively. The factors associated with psychological variables were social support, family role, fear of contagion, the desire to learn knowledge about COVID-19, and so on. Conclusion: Nurses who are of the Islamic culture are affected slightly by the COVID-19 outbreak, but their concern and factors associated with psychological variables are in keeping with the common nursing groups.

    Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study

    Authors: Ling Mao; Mengdie Wang; Shanghai Chen; Quanwei He; Jiang Chang; Candong Hong; Yifan Zhou; David Wang; Yanan Li; Huijuan Jin; Bo Hu

    doi:10.1101/2020.02.22.20026500 Date: 2020-02-25 Source: medRxiv

    OBJECTIVE: To study the neurological manifestations of patients with coronavirus disease MESHD 2019 (COVID-19). DESIGN: Retrospective case series SETTING: Three designated COVID-19 care hospitals of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. PARTICIPANTS: Two hundred fourteen hospitalized patients with laboratory confirmed diagnosis of severe acute respiratory syndrome MESHD from coronavirus 2 (SARS-CoV-2) infection MESHD. Data were collected from 16 January 2020 to 19 February 2020. MAIN OUTCOME MEASURES: Clinical data were extracted from electronic medical records and reviewed by a trained team of physicians. Neurological symptoms fall HP into three categories: central nervous system (CNS) symptoms or diseases ( headache HP headache MESHD, dizziness MESHD, impaired consciousness MESHD, ataxia HP ataxia MESHD, acute cerebrovascular disease MESHD, and epilepsy MESHD), peripheral nervous system (PNS) symptoms ( hypogeusia MESHD, hyposmia HP, hypopsia, and neuralgia MESHD), and skeletal muscular symptoms. Data of all neurological symptoms were checked by two trained neurologists. RESULTS: Of 214 patients studied, 88 (41.1%) were severe and 126 (58.9%) were non-severe patients. Compared with non-severe patients, severe patients were older (58.7 {+/-} 15.0 years vs 48.9 {+/-} 14.7 years), had more underlying disorders (42 [47.7%] vs 41 [32.5%]), especially hypertension HP hypertension MESHD (32 [36.4%] vs 19 [15.1%]), and showed less typical symptoms such as fever HP fever MESHD (40 [45.5%] vs 92 [73%]) and cough HP (30 [34.1%] vs 77 [61.1%]). Seventy-eight (36.4%) patients had neurologic manifestations. More severe patients were likely to have neurologic symptoms (40 [45.5%] vs 38 [30.2%]), such as acute cerebrovascular diseases MESHD (5 [5.7%] vs 1 [0.8%]), impaired consciousness MESHD (13 [14.8%] vs 3 [2.4%]) and skeletal muscle injury MESHD (17 [19.3%] vs 6 [4.8%]). CONCLUSION: Compared with non-severe patients with COVID-19, severe patients commonly had neurologic symptoms manifested as acute cerebrovascular diseases MESHD, consciousness impairment and skeletal muscle symptoms MESHD.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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