10 September, 2021

From Preprints

Misinformation - Aspects of susceptibility -

This paper analyzes the susceptibility to misinformation in a survey experiment by considering three hand-picked topics (climate change, Covid-19, and artificial intelligence). Subjects had to rate the reliability of several statements within these fields. We find evidence for a monological belief system (i.e., being susceptible to one statement containing misinformation is correlated with falling to other false news stories). Moreover, trust in social networks is positively associated with falling for misinformation. Whereas, there is some evidence that risk perception, willingness to think deliberately, actively open-minded thinking, and trust in science and media protects against being susceptible to misinformation. Surprisingly, the level of education does not seem to matter much.

🖺 Full Text HTML: Misinformation - Aspects of susceptibility

Psychological Trauma and Emotional Upheaval as Revealed in Academic Writing -

The current paper used a preregistered set of language dimensions to indicate how scientists psychologically managed the COVID-19 pandemic and its effects. Study 1 evaluated over 1.8 million preprints from arXiv.org and assessed how papers written during the COVID-19 pandemic reflected patterns of psychological trauma and emotional upheaval compared to those written before the pandemic. The data suggest papers written during the pandemic contained more affect (specifically, negative emotion), more cognitive processing terms to indicate writers working through a crisis, and less analytic thinking to indicate writers’ inward focus compared to papers written before the pandemic. Study 2 (N = 74,744 published PLoS One papers) observed consistent emotion results, but analytic thinking patterns were reversed. Papers written specifically about COVID-19 were also more emotional than those not written about COVID-19. Finally, Study 3 (N = 361,189 published papers) replicated the Study 2 emotion results across more diverse journals. These data suggest emotional upheavals are associated with psychological correlates reflected in the language of scientists at scale. Implications for psychology of language research and trauma are discussed.

🖺 Full Text HTML: Psychological Trauma and Emotional Upheaval as Revealed in Academic Writing

An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice -

Development of affordable and effective vaccines that can also protect vulnerable populations such as the elderly from COVID-19-related morbidity and mortality is a public health priority. Here we took a systematic and iterative approach by testing several SARS-CoV-2 protein antigens and adjuvants to identify a combination that elicits neutralizing antibodies and protection in young and aged mice. In particular, SARS-CoV-2 receptor-binding domain (RBD) displayed as a protein nanoparticle (RBD-NP) was a highly effective antigen, and when formulated with an oil-in-water emulsion containing Carbohydrate fatty acid MonoSulphate derivative (CMS) induced the highest levels of cross- neutralizing antibodies compared to other oil-in-water emulsions or AS01B. Mechanistically, CMS induced antigen retention in the draining lymph node (dLN) and expression of cytokines, chemokines and type I interferon-stimulated genes at both injection site and dLN. Overall, CMS:RBD-NP is effective across multiple age groups and is an exemplar of a SARS-CoV-2 subunit vaccine tailored to the elderly.

🖺 Full Text HTML: An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice

A virus-encoded microRNA contributes to evade innate immune response during SARS-CoV-2 infection -

SARS-CoV-2 infection results in impaired interferon response in severe COVID-19 patients. However, how SARS-CoV-2 interferes with host immune response is incompletely understood. Here, we sequenced small RNAs from SARS-CoV-2-infected human cells and identified a micro RNA (miRNA) encoded in a recently evolved region of the viral genome. We show that the virus-encoded miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer and they are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3’UTR of interferon-stimulated genes and represses their expression in a miRNA-like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID-19 patients. We propose that SARS-CoV-2 employs a virus-encoded miRNA to hijack the host miRNA machinery and evade the interferon-mediated immune response.

🖺 Full Text HTML: A virus-encoded microRNA contributes to evade innate immune response during SARS-CoV-2 infection

Targeting Stem-loop 1 of the SARS-CoV-2 5’UTR to suppress viral translation and Nsp1 evasion -

SARS-CoV-2 is a highly pathogenic virus that evades anti-viral immunity by interfering with host protein synthesis, mRNA stability, and protein trafficking. The SARS-CoV-2 nonstructural protein 1 (Nsp1) uses its C-terminal domain to block the mRNA entry channel of the 40S ribosome to inhibit host protein synthesis. However, how SARS-CoV-2 circumvents Nsp1-mediated suppression for viral protein synthesis and if the mechanism can be targeted therapeutically remain unclear. Here we show that N- and C-terminal domains of Nsp1 coordinate to drive a tuned ratio of viral to host translation, likely to maintain a certain level of host fitness while maximizing replication. We reveal that the SL1 region of the SARS-CoV-2 5’ UTR is necessary and sufficient to evade Nsp1-mediated translational suppression. Targeting SL1 with locked nucleic acid antisense oligonucleotides (ASOs) inhibits viral translation and makes SARS-CoV-2 5’ UTR vulnerable to Nsp1 suppression, hindering viral replication in vitro at a nanomolar concentration. Thus, SL1 allows Nsp1 to switch infected cells from host to SARS-CoV-2 translation, presenting a therapeutic target against COVID-19 that is conserved among immune-evasive variants. This unique strategy of unleashing a virus’ own virulence mechanism against itself could force a critical trade off between drug resistance and pathogenicity.

🖺 Full Text HTML: Targeting Stem-loop 1 of the SARS-CoV-2 5’UTR to suppress viral translation and Nsp1 evasion

SARS-CoV-2 triggers DNA damage response in Vero E6 cells -

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the current COVID-19 pandemic and has now infected more than 200 million people with more than 4 million deaths globally. Recent data suggest that symptoms and general malaise may continue long after the infection has ended in recovered patients, suggesting that SARS-CoV-2 infection has profound consequences in the host cells. Here we report that SARS-CoV-2 infection can trigger a DNA damage response (DDR) in African green monkey kidney cells (Vero E6). We observed a transcriptional upregulation of the Ataxia telangiectasia and Rad3 related protein (ATR) in infected cells. In addition, we observed enhanced phosphorylation of CHK1, a downstream effector of the ATR DNA damage response, as well as H2AX. Strikingly, SARS-CoV-2 infection lowered the expression of TRF2 shelterin-protein complex, and reduced telomere lengths in infected Vero E6 cells. Thus, our observations suggest SARS-CoV-2 may have pathological consequences to host cells beyond evoking an immunopathogenic immune response.

🖺 Full Text HTML: SARS-CoV-2 triggers DNA damage response in Vero E6 cells

Digital Spatial Profiling of Collapsing Glomerulopathy -

Collapsing glomerulopathy is a histologically distinct variant of focal and segmental glomerulosclerosis that presents with heavy proteinuria and portends a poor prognosis. Collapsing glomerulopathy can be triggered by viral infections such as HIV and SARS-CoV-2. Transcriptional profiling of collapsing glomerulopathy lesions is difficult since only a few glomeruli may exhibit this histology within a kidney biopsy and the mechanisms driving this heterogeneity are unknown. Therefore, we used recently developed digital spatial profiling (DSP) technology which permits quantification of mRNA at the level of individual glomeruli. Using DSP, we profiled 1,852 transcripts in glomeruli from HIV and SARS-CoV-2 infected patients with biopsy confirmed collapsing glomerulopathy. The increased resolution of DSP uncovered heterogeneity in glomerular transcriptional profiles that were missed in early laser capture microdissection studies of pooled glomeruli. Focused validation using immunohistochemistry and RNA in situ hybridization showed good concordance with DSP results. Therefore, DSP represents a powerful method to dissect transcriptional programs of pathologically discernible kidney lesions.

🖺 Full Text HTML: Digital Spatial Profiling of Collapsing Glomerulopathy

Heat efficiently inactivates coronaviruses inside vehicles -

Heat is an established method to inactivate coronaviruses, and there is utility in using heat to reduce viral load on common touch points in vehicles exposed to a person shedding SARS-CoV-2. As SARS-CoV-2 is a Biosafety level (BSL)-3 pathogen, real-world testing of heat as a sanitation method for public and private vehicles becomes a challenge, requiring a surrogate coronavirus that can be handled safely outside of a BSL-3 facility. In this study, we used Bovine Coronavirus (BCoV) as a surrogate for SARS-CoV-2 to test the efficacy of heat-based betacoronavirus inactivation. In vitro, a 30-minute exposure to 56{degrees}C completely inactivated BCoV in solution, and a 15-minute exposure reduced recovery of BCoV >1000-fold. When heated to 56{degrees}C for 15 minutes, the infectivity of BCoV spotted and dried on typical porous and non-porous automobile interior materials was reduced by 99 - 99.99%. When BCoV was spotted and dried on hard plastic (seat) material placed inside an out of service transit bus, 56{degrees}C heat for 30 minutes reduced BCoV infectivity 85 - 99.5%. Thus, 56{degrees}C is an accessible, rapid, and effective method to inactivate coronaviruses inside motor vehicles.

🖺 Full Text HTML: Heat efficiently inactivates coronaviruses inside vehicles

A thermostable oral SARS-CoV-2 vaccine induces mucosal and protective immunity -

An ideal protective vaccine against SARS-CoV-2 should not only be effective in preventing disease, but also in preventing virus transmission. It should also be well accepted by the population and have a simple logistic chain. To fulfill these criteria, we developed a thermostable, orally administered vaccine that can induce a robust mucosal neutralizing immune response. We used our platform based on retrovirus-derived enveloped virus-like particles (e-VLPs) harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia, affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration. We made e-VLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with or without membrane protein (M) expression. We found that prime-boost administration of VSP-decorated e-VLPs expressing a pre-fusion stabilized form of S and M triggers robust mucosal responses against SARS-CoV-2 in mice and hamsters, which translate into complete protection from a viral challenge. Moreover, they dramatically boosted the IgA mucosal response of intramuscularly injected vaccines. We conclude that our thermostable orally administered e-VLP vaccine could be a valuable addition to the current arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategy or as a boost for existing vaccines.

🖺 Full Text HTML: A thermostable oral SARS-CoV-2 vaccine induces mucosal and protective immunity

Circulating multimeric immune complexes drive immunopathology in COVID-19 -

A dysregulated immune response with high levels of SARS-CoV-2 specific IgG antibodies characterizes patients with severe or critical COVID-19. Although a robust IgG response is traditionally considered to be protective, excessive triggering of activating Fc-gamma-receptors (Fc{gamma}Rs) could be detrimental and cause immunopathology. Here, we document that patients who develop soluble circulating IgG immune complexes (sICs) during infection are subject to enhanced immunopathology driven by Fc{gamma}R activation. Utilizing cell-based reporter systems we provide evidence that sICs are predominantly formed prior to a specific humoral response against SARS-CoV-2. sIC formation, together with increased afucosylation of SARS-CoV-2 specific IgG eventually leads to an enhanced CD16 (Fc{gamma}RIII) activation of immune cells reaching activation levels comparable active systemic lupus erythematosus (SLE) disease. Our data suggest a vicious cycle of escalating immunopathology driven by an early formation of sICs in predisposed patients. These findings reconcile the seemingly paradoxical findings of high antiviral IgG responses and systemic immune dysregulation in severe COVID-19.

🖺 Full Text HTML: Circulating multimeric immune complexes drive immunopathology in COVID-19

LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants -

LY-CoV1404 (also known as bebtelovimab) is a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient sample, obtained approximately 60 days after symptom onset. In pseudovirus studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.617.2, B.1.1.7, B.1.351, B.1.427/B.1.429, P.1, and B.1.526, binding to these variants in the presence of their underlying RBD mutations (which include K417N, L452R, E484K, and N501Y). LY-CoV1404 also neutralizes multiple isolates of the authentic SARS-CoV-2 virus in two different assays. The RBD positions comprising the LY-CoV1404 epitope are highly conserved, with the exception of N439 and N501; notably the binding and neutralizing activity of LY- CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). New variant-resistant treatments such as LY-CoV1404 are desperately needed, given that some of the existing therapeutic antibodies are less effective or ineffective against certain variants and the impact of variants on vaccine efficacy is still poorly understood. The breadth of variant binding, potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 is one in a panel of well-characterized, clinically developable antibodies that could be deployed as potentially long-term solutions to address current and emerging variants.

🖺 Full Text HTML: LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants

Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants -

Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2G{Delta}HR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with the same potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2G{Delta}HR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in mice. Compared with the soluble spike, the I3-01v9 SApNP showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold stronger germinal center reactions in lymph node follicles.

🖺 Full Text HTML: Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

A Learning Health System Randomized Trial of Monoclonal Antibodies for Covid-19 -

ABSTRACT Background: Neutralizing monoclonal antibodies (mAb) targeting SARS CoV2 decrease hospitalization and death in patients with mild to moderate Covid 19. Yet, their clinical use is limited, and comparative effectiveness is unknown. Methods: We present the first results of an ongoing, learning health system adaptive platform trial to expand mAb treatment to all eligible patients and evaluate the comparative effectiveness of available mAbs. The trial launched March 10, 2021. Results are reported as of June 25, 2021 due to the U.S. federal decision to pause distribution of bamlanivimab etesevimab; patient follow-up concluded on July 23, 2021. Patients referred for mAb who met Emergency Use Authorization criteria were provided a random mAb allocation of bamlanivimab, bamlanivimab etesevimab, or casirivimab imdevimab with a therapeutic interchange policy. The primary outcome was hospital-free days (days alive and free of hospital) within 28 days, where patients who died were assigned -1 day. The primary analysis was a Bayesian cumulative logistic model of all patients treated at an infusion center or emergency department, adjusting for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio < 1. Equivalence was defined as a 95% posterior probability that the odds ratio is within a given bound. Results: Prior to trial launch, 3.1%

of 16,345 patients who were potentially eligible by an automated electronic health record (EHR) screen received mAb. During the trial period, 23.2% (1,201) of 5,173 EHR-screen eligible patients were treated, a 7.5-fold increase. After including additional referred patients from outside the health system, a total of 1,935 study patients received mAb therapy (128 bamlanivimab, 885 bamlanivimab etesevimab, 922 casirivimab imdevimab). Mean age ranged from 55 to 57 years, half were female (range, 53% to 54%), and 17% were Black (range, 12% to 19%). Median hospital free days were 28 (IQR, 28 to 28) for each mAb group. Hospitalization varied between groups (bamlanivimab, 12.5%; bamlanivimab etesevimab, 14.7%, casirivimab imdevimab, 14.3%). Relative to casirivimab-imdevimab, the median adjusted odds ratios were 0.58 (95% credible interval (CI), 0.30 to 1.16) and 0.94 (95% CI, 0.72 to 1.24) for the bamlanivimab and bamlanivimab-etesevimab groups, respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab etesevimab and casirivimab imdevimab respectively, and an 86% probability of equivalence between bamlanivimab etesevimab and casirivimab imdevimab, at the prespecified odds ratio bound of 0.25. Twenty one infusion related adverse events occurred in 0% (0/128), 1.4% (12/885), and 1.0% (9/922) of patients treated with bamlanivimab, bamlanivimab etesevimab, and casirivimab imdevimab, respectively. Conclusion: In non-hospitalized patients with mild to moderate Covid-19, bamlanivimab, compared to bamlanivimab etesevimab and casirivimab imdevimab, resulted in 91% and 94% probabilities of inferiority with regards to odds of improvement in hospital free days within 28 days. There was an 86% probability of equivalence between bamlanivimab etesevimab and casirivimab imdevimab at an odds ratio bound of 0.25. However, the trial was unblinded early due to federal distribution decisions, and no mAb met prespecified criteria for statistical inferiority or equivalence. (ClinicalTrials.gov, NCT04790786).

🖺 Full Text HTML: A Learning Health System Randomized Trial of Monoclonal Antibodies for Covid-19

The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 Beta (B.1.351) and other variants of concern in preclinical studies. -

There is an ongoing global effort, to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations that negatively impact the role of neutralising antibodies. In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine against the variant of concern B.1.351 (AZD2816). We demonstrate AZD2816 is immunogenic after a single dose and when used as a booster dose in animals primed with original vaccine AZD1222, we see no evidence of original antigenic sin but high titre antibodies against a number of variant spike proteins. In addition, neutralisation titres against B.1.351 (Beta), B.1.617.1 (Kappa) and B.1.617.2 (Delta), are induced in these boost regimens. These data support the ongoing clinical development and testing of this new variant vaccine.

🖺 Full Text HTML: The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 Beta (B.1.351) and other variants of concern in preclinical studies.

Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2 -

The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single- cell RNA sequencing and proteomics to a primary cell model of human nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrated widespread tropism for nasal epithelial cell types. The host response was dominated by type I and III IFNs and interferon-stimulated gene products. This response was notably delayed in onset relative to viral gene expression and compared to other respiratory viruses. Nevertheless, once established, the paracrine IFN response began to impact on SARS-CoV-2 replication. When provided prior to infection, recombinant IFN{beta} or IFN{lambda}1 induced an efficient antiviral state that potently restricted SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data suggest that the IFN-I/III response to SARS-CoV-2 initiates in the nasal airway and suggest nasal delivery of recombinant IFNs to be a potential chemoprophylactic strategy.

🖺 Full Text HTML: Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS- CoV-2

From Clinical Trials

High-dose Intravenous Vitamin C (HDIVC) as Adjuvant Therapy in Critical Patients With Positive COVID-19. A Pilot Randomized Controlled Dose-comparison Trial. - Condition: Covid19
Interventions: Drug: High doses of intravenous vitamin C; Drug: Dextrose 500 mL
Sponsor: Hugo Galindo
Not yet recruiting

Developing and Testing a COVID-19 Vaccination Acceptance Intervention - Condition: COVID-19 Vaccination
Intervention: Behavioral: Moving to COVID-19 Vaccine Acceptance Intervention
Sponsors: VA Office of Research and Development; VA Bedford Healthcare System
Not yet recruiting

Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected) - Condition: COVID-19
Interventions: Drug: AZVUDINE; Drug: AZVUDINE placebo
Sponsors: HRH Holdngs Limited; GALZU INSTITUTE OF RESEARCH, TEACHING, APPLIED SCIENCE AND TECHNOLOGY, Brazil; SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil; UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
Not yet recruiting

COVID-19 Morbidity in Healthcare Workers and Vitamin D Supplementation - Condition: COVID-19 Respiratory Infection
Intervention: Drug: Vitamin D
Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Completed

Text Message Nudges for COVID-19 Vaccination - Condition: Covid19
Intervention: Behavioral: Text message
Sponsor:
Ascension South East Michigan
Not yet recruiting

Quercetin in the Prevention of Covid-19 Infection - Condition: Covid19
Interventions: Dietary Supplement: Quercetin; Combination Product: Placebo
Sponsor: Azienda di Servizi alla Persona di Pavia
Completed

A Study to Evaluate Change in Viral Load After OPN-019 in Adults With COVID-19 - Condition: Covid19
Intervention: Drug: OPN-019
Sponsor: Optinose US Inc.
Recruiting

Physical Activity and Smell Trainings to Help Individuals With Coronavirus Disease (COVID-19) Recover From Persistent Smell and Taste Impairments - A Pilot Study - Condition: Covid19
Interventions: Behavioral: Physical activity; Other: Smell training
Sponsor: Université de Montréal
Not yet recruiting

Evaluation of the Efficacy, Safety and Immunogenicity of Inactivated COVID 19 Vaccine(TURKOVAC) in Healthy Population of 18 and 64 Years of Age (Both Inclusive):a Randomized, Double-blind, Phase IIb Clinical Trial - Condition: Covid19
Intervention: Biological: Triple dose vaccination by inactivated Covid19 vaccine
Sponsors: Health Institutes of Turkey; TC Erciyes University; Kocak Farma; Mene Research
Not yet recruiting

Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue - Condition: COVID-19 Respiratory Infection
Intervention:
Other: Cardiopulmonary exercise training
Sponsor: Louis Bherer
Recruiting

Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions: COVID-19 Pneumonia; Coronavirus Infections
Interventions: Biological: Recombinant COVID-19 Vaccine (CHO cell); Biological: COVID-19 vaccine (Vero cells)
Sponsors:
National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd
Not yet recruiting

Study to Evaluate the Efficacy and Safety of Colchicine Tablets in Patients With COVID-19 - Conditions: Covid19; Colchicine
Interventions: Drug: Colchicine Tablets; Drug: Standard therapy
Sponsors: Shanghai Public Health Clinical Center; Kunming Pharmaceuticals, Inc.
Not yet recruiting

Comparison of Detection of SARS-CoV2 (COVID-19) Between Nasopharyngeal Swab Specimens and Those Obtained by Salivary Sputum - Condition: Covid19
Intervention: Diagnostic Test: Salivary test for COVID19
Sponsor: Centre Hospitalier de Cayenne
Active, not recruiting

Phase 2a MIB-626 vs. Placebo COVID-19 - Conditions: Covid19; Stage 1 Acute Kidney Injury
Interventions: Drug: MIB-626; Drug: Placebo; Other: Home Treatment
Sponsor: Metro International Biotech, LLC
Not yet recruiting

Clinical Study of the Safety and Immunogenicity of a Recombinant Viral Vector AAV5 (Adeno-Associated Virus Type 5 )-RBD (Receptor Binding Domain)-S Vaccine for the Prevention of Coronavirus Infection (COVID-19) - Conditions: Coronavirus Infection; COVID-19
Interventions:
Biological: Low dose BCD-250 injection; Biological: High dose BCD-250 injection; Biological: Low dose or high dose BCD-250 injection; Other: Placebo injection
Sponsor: Biocad
Recruiting

From PubMed

Remdesivir and EIDD-1931 Interact with Human Equilibrative Nucleoside Transporters 1 and 2: Implications for Reaching SARS-CoV-2 Viral Sanctuary Sites - Equilibrative nucleoside transporters (ENTs) are present at the blood-testis barrier (BTB), where they can facilitate antiviral drug disposition to eliminate a sanctuary site for viruses detectable in semen. The purpose of this study was to investigate ENT-drug interactions with three nucleoside analogs remdesivir, molnupiravir and its active metabolite, EIDD-1931 and four non-nucleoside molecules repurposed as antivirals for COVID-19. The study used 3D pharmacophores for ENT1 and ENT2…

Identifying FDA-approved drugs with multimodal properties against COVID-19 using a data-driven approach and a lung organoid model of SARS-CoV-2 entry - CONCLUSIONS: Small clinical studies reported that general statin use, and specifically, atorvastatin use, are associated with protective effects against COVID-19. Our study corroborrates these findings and supports the investigation of atorvastatin in larger clinical studies. Ultimately, our framework demonstrates one promising way to fast-track the identification of compounds for COVID-19, which could similarly be applied when tackling future pandemics.

Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease - The SARS-CoV-2 main protease (M^(pro)) is one of the molecular targets for drug design. Effective vaccines have been identified as a long-term solution but the rate at which they are being administered is slow in several countries, and mutations of SARS-CoV-2 could render them less effective. Moreover, remdesivir seems to work only with some types of COVID-19 patients. Hence, the continuous investigation of new treatments for this disease is pivotal. This study investigated the inhibitory role…

Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90 - SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the causative agent of the COVID19 pandemic. The SARS- CoV-2 genome encodes for a small accessory protein termed Orf9b, which targets the mitochondrial outer membrane protein TOM70 in infected cells. TOM70 is involved in a signaling cascade that ultimately leads to the induction of type I interferons (IFN-I). This cascade depends on the recruitment of Hsp90-bound proteins to the N-terminal domain of TOM70. Binding of Orf9b to TOM70…

Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, M(pro) and PL(pro) of SARS-CoV-2: Protein-Protein Interactions, Dynamics Simulations and Free Energy Calculations - The emergence of COVID-19 continues to pose severe threats to global public health. The pandemic has infected over 171 million people and claimed more than 3.5 million lives to date. We investigated the binding potential of antiviral cyanobacterial proteins including cyanovirin-N, scytovirin and phycocyanin with fundamental proteins involved in attachment and replication of SARS-CoV-2. Cyanovirin-N displayed the highest binding energy scores (-16.8 ± 0.02 kcal/mol, -12.3 ± 0.03 kcal/mol and…

In silico evaluation of COVID-19 main protease interactions with honeybee natural products for discovery of high potential antiviral compounds - This research investigates antiviral potential of extracted honeybee products against COVID-19 main protease (Mpro) by computational methods. The crystal structure of COVID-19 Mpro was obtained from the protein data bank. Six synthetic drugs with antiviral properties were used as control samples in order to compare the results with those of natural ligands. The six honeybee components, namely 3,4,5-Tricaffeoylquinic acid, Kaempferol-3-O-glucoside, (E)-2’-Geranyl-3’,4’,7-Trihydroxyflavanone,…

Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread - COVID-19 is caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2). The virus is responsible for an ongoing pandemic and concomitant public health crisis around the world. While vaccine development is proving to be highly successful, parallel drug development approaches are also critical in the response to SARS-CoV-2 and other emerging viruses. Coronaviruses require Ca^(2+) ions for host cell entry, and we have previously shown that Ca^(2+)…

A novel competition ELISA for the rapid quantification of SARS-CoV-2 neutralizing antibodies in convalescent plasma - CONCLUSION: The competition ELISA screens for neutralizing antibodies in CCP by competition for just a single epitope. It exerts a sensitivity of 61% with no false identifications. These ELISA designs can be used for epitope mapping or for selection of CCP.

Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease - We present a detailed computational analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against the SARS-CoV-2 3CL protease. Alchemical free energy calculations suggest that positions P3 and P4 could be susceptible to improvement in order to get a larger binding strength. QM/MM simulations unveil the reaction mechanism for covalent inhibition, showing that the nitrile warhead facilitates the recruitment of a water molecule for the proton transfer step.

Transcriptomic Signatures of Airway Epithelium Infected With SARS-CoV-2: A Balance Between Anti-infection and Virus Load - COVID-19 pneumonia requires effective medical therapies. However, it is a challenge to find therapeutic drugs that not only inhibit viral replication, but also inhibit the accompanying cytokine storm and maintain an appropriate immune response. In this study, the effects of SARS-CoV-2 on gene expression in lung epithelial cells from patients with COVID-19 were systematically evaluated with bioinformatics analysis methods. Transcriptome expression specific to bystander (exposed but uninfected)…

The Antiviral Roles of Hydrogen Sulfide by Blocking the Interaction between SARS-CoV-2 and Its Potential Cell Surface Receptors - The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is posing a great threat to the global economy and public health security. Together with the acknowledged angiotensin-converting enzyme 2, glucose-regulated protein 78, transferrin receptor, AXL, kidney injury molecule-1, and neuropilin 1 are also identified as potential receptors to mediate SARS-CoV-2 infection. Therefore, how to inhibit or delay the binding of…

Long-Term Persistence and Relevant Therapeutic Impact of High-Titer Viral-Neutralizing Antibody in a Convalescent COVID-19 Plasma Super-Donor: A Case Report - A convalescent, non-severe, patient with COVID-19 was enrolled as a hyper-immune plasma voluntary donor by the Immuno- Hematology and Transfusion Unit of the Regina Elena National Cancer Institute in Rome, under the TSUNAMI national study criteria. During a nearly 6-month period (May-October 2020), the patient was closely monitored and underwent four hyperimmune plasma collections. Serum SARS-CoV-2 (anti-S + anti-N) IgG and IgM, anti-S1 IgA, and neutralizing titers (NTs) were measured….

mTOR-Inhibition and COVID-19 in Kidney Transplant Recipients: Focus on Pulmonary Fibrosis - Kidney transplant recipients are at high risk of developing severe COVID-19 due to the coexistence of several transplant-related comorbidities (e.g., cardiovascular disease, diabetes) and chronic immunosuppression. As a consequence, a large part of SARS-CoV-2 infected patients have been managed with a reduction of immunosuppression. The mTOR-I, together with antimetabolites, have been often discontinued in order to minimize the risk of pulmonary toxicity and to antagonize pharmacological…

Interactions of anti-COVID-19 drug candidates with hepatic transporters may cause liver toxicity and affect pharmacokinetics - Transporters in the human liver play a major role in the clearance of endo- and xenobiotics. Apical (canalicular) transporters extrude compounds to the bile, while basolateral hepatocyte transporters promote the uptake of, or expel, various compounds from/into the venous blood stream. In the present work we have examined the in vitro interactions of some key repurposed drugs advocated to treat COVID-19 (lopinavir, ritonavir, ivermectin, remdesivir and favipiravir), with the key drug transporters…

In vitro efficacy of Artemisia extracts against SARS-CoV-2 - CONCLUSIONS: Some plant extracts show inhibitory activity against FCoV and SARS-CoV-2. However, it remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral infection following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment of patients.

From Patent Search

MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

Anti-Sars-Cov-2 Neutralizing Antibodies - - link

Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

SARS-COV-2 BINDING PROTEINS - - link

COVID-19胸部CT图像识别方法、装置及电子设备 - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像，并针对胸部CT图像的特点，构建新冠肺炎CT识别网络，对该网络进行训练得到COVID‑19胸部CT图像识别模型，并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子，减少冗余参数；采用并行结构连接方式，实现多尺度特征融合、降低模型复杂度；采用下采样方式，使用最大模糊池化以减少锯齿效应，保持信号的平移不变性；采用通道混洗操作，减少参数量与计算量，提高分类准确率，引入坐标注意力机制，使空间坐标信息与通道信息被关注，抑制不重要的信息，以解决资源匹配问题。 - link

A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link

IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link

一种脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂 - 本发明属于基因治疗技术领域，具体涉及一系列脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂。本发明提供的具有式（I）结构的化合物，可与其它脂质化合物共同制备脂质载体，展现出pH响应性，对核酸药物的包封效率高，大大提升了核酸药物在体内的递送效率；而且，可根据核酸药物需要富集的器官而选用特定结构的脂质化合物作为脂质载体，具有良好的市场应用前景。 - link

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