Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• “Saving lives, protecting livelihoods, and safeguarding nature”: risk-based wildlife trade policy for sustainable development outcomes post-COVID-19 -
  The COVID‐19 pandemic has caused huge loss of life, and immense social and economic harm. Wildlife trade has become central to discourse on COVID-19, zoonotic pandemics, and related policy responses, which must focus on “saving lives, protecting livelihoods, and safeguarding nature”. Proposed policy responses have included extreme measures such as banning all use and trade of wildlife, or blanket measures for entire Classes. However, different trades pose varying degrees of risk for zoonotic pandemics, while some trades also play critical roles in delivering other aspects of sustainable development, particularly related to poverty, hunger, decent work, responsible consumption and production, and life on land and below water. Here we describe how wildlife trade contributes to the UN Sustainable Development Goals (SDGs) in diverse ways, with synergies and trade-offs within and between the SDGs. In doing so, we show that prohibitions could result in severe trade-offs against some SDGs, with limited benefits for public health via pandemic prevention. This complexity necessitates context-specific policies, with multi-sector decision-making that goes beyond simple top-down solutions. We encourage decision-makers to adopt a risk-based approach to wildlife trade policy post-COVID-19, with policies formulate via participatory, evidence-based approaches, which explicitly acknowledge uncertainty, complexity and conflicting values across different components of the SDGs. This could help to ensure that future use and trade of wildlife is safe, environmentally-sustainable and socially-just.
  🖺 Full Text HTML: “Saving lives, protecting livelihoods, and safeguarding nature”: risk-based wildlife trade policy for sustainable development outcomes post-COVID-19
• High affinity modified ACE2 receptors protect from SARS-CoV-2 infection in hamsters -
  The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor via receptor binding domain (RBD) to enter into the cell and inhibiting this interaction is a main approach to inhibit SARS-CoV-2 infection. We engineered ACE2 to enhance the affinity with directed evolution in 293T cells. Three cycles of random mutation and cell sorting achieved 100-fold higher affinity to RBD than wild-type ACE2. The extracellular domain of modified ACE2 fused to the human IgG1-Fc region had stable structure and neutralized SARS-CoV-2 without the emergence of mutational escape. Therapeutic administration protected hamsters from SARS-CoV-2 infection, decreasing lung virus titers and pathology. Engineering ACE2 decoy receptors with human cell-based directed evolution is a promising approach to develop a SARS-CoV-2 neutralizing drug that has affinity comparable to monoclonal antibodies yet displaying resistance to escape mutations of virus.
  🖺 Full Text HTML: High affinity modified ACE2 receptors protect from SARS-CoV-2 infection in hamsters
• First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain -

  Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.

  🖺 Full Text HTML: First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain
• Emotions, reasoning, and mental health as predictors of behavior during three phases of the COVID-19 pandemic -
  The COVID-19 pandemic has required people worldwide to adjust their behavior for several months in response to a crisis of rare proportions. Little is known about the specific factors that affected the progression of the public’s reactions during the pandemic. Individual factors associated with pandemic-related behavior in general, and compliance with public health measures in particular, are not firmly established. We undertook a survey of behavior, emotions, reasoning style, and mental health in the province of Quebec at the beginning, the peak, and the aftermath of the first wave of the COVID-19 pandemic. We recruited 530 responders from a convenience sample; 154 responders participated in all three surveys. Emotions were most intense at the beginning of the first wave of the pandemic, not at its peak. Responders’ compliance with three public health measures decreased between the peak and the aftermath of the first wave of the pandemic; however, mask wearing also became more common. Pandemic-related behavior in general, and compliance with public health measures specifically, were predicted by avoidance-related emotions evoked by the pandemic. Approach-related emotions linked to the societal response contributed specifically to the prediction of compliance with public health measures. In contrast, reasoning style and mental health did not as consistently predict behavior during the pandemic. Our research may help inform public health policy during other waves of the COVID-19 pandemic and future global health crises.
  🖺 Full Text HTML: Emotions, reasoning, and mental health as predictors of behavior during three phases of the COVID-19 pandemic
• Study of relationship between optimism and resilience in the times of COVID-19 among university students -
  The purpose of present research is to study the effect of COVID-19 Pandemic on the relationship between Optimism and Resilience among the university students. Optimism and Resilience of 100 university students (36 males and 64 females) were assessed by using optimism pessimism scale and a brief resilience scale. Digital survey method was adopted to reach out to the university students between 18-23 yrs. of age group and Pearson correlation coefficient method was used to establish the relationship between the variables. As a result, it was found that optimism and resilience share a positive relationship (0.507) not only otherwise but in the challenging times too. Findings revealed that to increase the resilience one has to increase the positive and optimistic thoughts. The research can add value to the detailed study on optimism and its relation with resilience and psychological well-being during unforeseen period. This study also gives further opportunity for a comparative study between the optimism and resilience among different age groups.
  🖺 Full Text HTML: Study of relationship between optimism and resilience in the times of COVID-19 among university students
• Impact of mass testing during an epidemic rebound of SARS-CoV-2: A modelling study -

  We used a mathematical model to evaluate the impact of mass testing in the control of SARS-CoV-2. Conditions required to control a quickly growing epidemic with mass testing appear impossible to achieve. Mass testing should therefore not be seen as a silver bullet that will ensure other control measures can be removed. Even under a set of optimistic assumptions, this strategy is most relevant when epidemic growth remains limited, thanks to a combination of interventions.

  🖺 Full Text HTML: Impact of mass testing during an epidemic rebound of SARS-CoV-2: A modelling study
• Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among Hospital Workers - a multicentre cross-sectional study -

  Objectives Protecting healthcare workers (HCW) from Coronavirus Disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) seropositivity in this population. Methods Between June 22nd and August 15th 2020, HCW from institutions in Northern/Eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity. Results Among 4664 HCW from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR=54, 95%-CI: 31-97) and stay in a COVID 19 hotspot (aOR=2.2, 95%-CI: 1.1-3.9). Blood group 0 vs. non-0 (aOR=0.4, 95%-CI: 0.3-0.7), active smoking (aOR=0.5, 95%-CI: 0.3-0.9) and living with children <12 years (aOR=0.3, 95%-CI: 0.2-0.6) were associated with decreased risk. Occupational risk factors were close contact to COVID-19 patients (aOR=2.8, 95%-CI: 1.5-5.5), exposure to COVID-19-positive co-workers (aOR=2.0, 95%-CI: 1.2-3.1), poor knowledge of standard hygiene precautions (aOR=2.0, 95%-CI: 1.3-3.2), and frequent visits to the hospital canteen (aOR=1.9, 95%-CI: 1.2-3.1). Conclusions Living with COVID-19-positive households showed by far the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable risk factors, which might allow mitigation of the COVID-19 risk among HCW. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study.

  🖺 Full Text HTML: Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among Hospital Workers - a multicentre cross-sectional study
• Social and racial inequalities in COVID-19 risk of hospitalisation and death across Sao Paulo state, Brazil -

  Background: Little evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in Sao Paulo state, Brazil and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities. Methods: We conducted a cross-sectional study using hospitalised severe acute respiratory infections (SARI) notified from March to August 2020, in the Sistema de Monitoramento Inteligente de Sao Paulo (SIMI-SP) database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple datasets for individual-level and spatio-temporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour, and comorbidities. Findings: Throughout the study period, patients living in the 40% poorest areas were more likely to die when compared to patients living in the 5% wealthiest areas (OR: 1.60, 95% CI: 1.48 - 1.74) and were more likely to be hospitalised between April and July, 2020 (OR: 1.08, 95% CI: 1.04 - 1.12). Black and Pardo individuals were more likely to be hospitalised when compared to White individuals (OR: 1.37, 95% CI: 1.32 - 1.41; OR: 1.23, 95% CI: 1.21 - 1.25, respectively), and were more likely to die (OR: 1.14, 95% CI: 1.07 - 1.21; 1.09, 95% CI: 1.05 - 1.13, respectively). Interpretation: Low-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to healthcare, adherence to social distancing, and the higher prevalence of comorbidities.

  🖺 Full Text HTML: Social and racial inequalities in COVID-19 risk of hospitalisation and death across Sao Paulo state, Brazil
• Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies -
  SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.
  🖺 Full Text HTML: Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies
• SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome -
  Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.
  🖺 Full Text HTML: SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
• Generation of a SARS-CoV-2 Replicon as a Model System to Dissect Virus Replication and Antiviral Inhibition -
  SARS-CoV-2 research and antiviral discovery are hampered by the lack of a cell-based virus replication system that can be readily adopted without biosafety level 3 (BSL-3) restrictions. Here, the construction of a non-infectious SARS-CoV-2 reporter replicon and its application in deciphering viral replication mechanisms and evaluating SARS-CoV-2 inhibitors are presented. The replicon genome is replication competent but does not produce progeny virions. Its replication can be inhibited by RdRp mutations or by known SARS-CoV-2 antiviral compounds. Using this system, a high-throughput antiviral assay has also been developed. Significant differences in potencies of several SARS-CoV-2 inhibitors in different cell lines were observed, which highlights the challenges of discovering antivirals capable of inhibiting viral replication in vivo and the importance of testing compounds in multiple cell culture models. The generation of a SARS-CoV-2 replicon provides a powerful platform to expand the global research effort to combat COVID-19.
  🖺 Full Text HTML: Generation of a SARS-CoV-2 Replicon as a Model System to Dissect Virus Replication and Antiviral Inhibition
• A novel cell culture system modeling the SARS-CoV-2 life cycle -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the global pandemic of COVID-19, and no effective antiviral agents and vaccines are available. SARS-CoV-2 is classified as a biosafety level-3 (BLS-3) agent, impeding the basic research into its biology and the development of effective antivirals. Here, we developed a biosafety level-2 (BSL-2) cell culture system for production of transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). This trVLP expresses a reporter gene (GFP) replacing viral nucleocapsid gene (N), which is required for viral genome packaging and virion assembly (SARS-CoV-2-GFP/{Delta}N trVLP). The complete viral life cycle can be achieved and exclusively confined in the cells ectopically expressing SARS-CoV or SARS-CoV-2 N proteins, but not MERS-CoV N. Genetic recombination of N supplied in trans into viral genome was not detected, as evidenced by sequence analysis after one-month serial passages in the N-expressing cells. Moreover, intein-mediated protein trans-splicing approach was utilized to split the viral N gene into two independent vectors, and the ligated viral N protein could function in trans to recapitulate entire viral life cycle, further securing the biosafety of this cell culture model. Based on this BSL-2 SARS-CoV-2 cell culture model, we developed a 96-well format high throughput screening for antivirals discovery. We identified salinomycin, tubeimoside I, monensin sodium, lycorine chloride and nigericin sodium as potent antivirals against SARS-CoV-2 infection. Collectively, we developed a convenient and efficient SARS-CoV-2 reverse genetics tool to dissect the virus life cycle under a BSL-2 condition. This powerful tool should accelerate our understanding of SARS-CoV-2 biology and its antiviral development.
  🖺 Full Text HTML: A novel cell culture system modeling the SARS-CoV-2 life cycle
• Evaluation of in vitro activity of copper gluconate against SARS-CoV-2 using confocal microscopy-based high content screening -
  Context: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that emerged late in 2019 is the etiologic agent of coronavirus disease 2019 (Covid-19). There is an urgent need to develop curative and preventive therapeutics to limit the current pandemic and to prevent the re-emergence of Covid-19. This study aimed to assess the in vitro activity of copper gluconate against SRAS-CoV-2. Methods: Vero E6 cells were treated with copper gluconate 18 hours before infection. Cells were infected with a recombinant GFP expressing SARS-CoV-2. Infected cells were maintained in fresh medium containing copper gluconate for an additional 48-hour period. The infection level was measured by the confocal microscopy-based high content screening method. The cell viability in presence of copper gluconate was assessed by XTT assay. Results: The viability of Vero E6 cells treated with copper gluconate up to 200 M was found to be similar to that of untreated cells, but it dropped below 40% with 400 M of this agent. The infection rate was 23.8%, 18.9%, 20.6%, 6.9%, 5.3%,5.2% in cells treated with 0, 2, 10, 25, 50 and 100 M of copper gluconate respectively. As compared to untreated cells, the number of infected cells was reduced by 71%, 77%, and 78% with 25, 50, and 100 M of copper gluconate respectively (p < 0.05). Conclusion: Copper gluconate was found to mitigate SARS-CoV-2 infection in Vero E6 cells. Furthers studies are needed to determine whether copper homeostasis could play a role in SARS-CoV-2 infection.
  🖺 Full Text HTML: Evaluation of in vitro activity of copper gluconate against SARS-CoV-2 using confocal microscopy-based high content screening
• The Potential for SARS-CoV-2 to Evade Both Natural and Vaccine-induced Immunity -
  SARS-CoV-2 attaches to the surface of susceptible cells through extensive interactions between the receptor binding domain (RBD) of its spike protein and angiotensin converting enzyme type 2 (ACE2) anchored in cell membranes. To investigate whether naturally occurring mutations in the spike protein are able to prevent antibody binding, yet while maintaining the ability to bind ACE2 and viral infectivity, mutations in the spike protein identified in cases of human infection were mapped to the crystallographically-determined interfaces between the spike protein and ACE2 (PDB entry 6M0J), antibody CC12.1 (PDB entry 6XC2), and antibody P2B-2F6 (PDB entry 7BWJ). Both antibody binding interfaces partially overlap with the ACE2 binding interface. Among 16 mutations that map to the RBD:CC12.1 interface, 11 are likely to disrupt CC12.1 binding but not ACE2 binding. Among 12 mutations that map to the RBD:P2B-2F6 interface, 8 are likely to disrupt P2B-2F6 binding but not ACE2 binding. As expected, none of the mutations observed to date appear likely to disrupt the RBD:ACE2 interface. We conclude that SARS-CoV-2 with mutated forms of the spike protein may retain the ability to bind ACE2 while evading recognition by antibodies that arise in response to the original wild-type form of the spike protein. It seems likely that immune evasion will be possible regardless of whether the spike protein was encountered in the form of infectious virus, or as the immunogen in a vaccine. Therefore, it also seems likely that reinfection with a variant strain of SARS-CoV-2 may occur among people who recover from Covid-19, and that vaccines with the ability to generate antibodies against multiple variant forms of the spike protein will be necessary to protect against variant forms of SARS-CoV-2 that are already circulating in the human population.
  🖺 Full Text HTML: The Potential for SARS-CoV-2 to Evade Both Natural and Vaccine-induced Immunity
• Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis -

  Background: Antipsychotics suppress expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID versus COVID RNA-Seq samples (CRA002390 project in GSA database) and drug-naive patients with psychosis at baseline and after three months of aripiprazole treatment was identified. An integrative analysis between COVID and aripiprazole immunomodulatory antagonist effects was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher9s Exact Test, two tail; P value=3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated schizophrenia patients (P adj<0.05). The most significant pathways were associated to the immune system such as the inflammatory bowel disease (IBD) (the most significant pathway with a P adj of 0.00021), Th1 and Th2 cell differentiation and B cell receptor signaling pathway, all three related to the defense against infections. Interpretation: This exploratory investigation may provide further support to the notion that protective effect is exerted by phenylpiperazine by modulating the immunological dysregulation associated to COVID-19. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.

  🖺 Full Text HTML: Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis

From Clinical Trials

• Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19 - Condition:   Covid19
  Interventions:   Drug: Silmitasertib;   Drug: SOC
  Sponsor:   Chris Recknor, MD
  Recruiting

• Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 convalescent plasma;   Other: Standard of care
  Sponsors:   Joakim Dillner;   Karolinska Institutet;   Danderyd Hospital;   Falu Hospital
  Not yet recruiting

• Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19) - Condition:   COVID-19
  Interventions:   Biological: Group A (AG0302-COVID19);   Biological: Group A (Placebo);   Biological: Group B (AG0302-COVID19);   Biological: Group B (Placebo)
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Recruiting

• Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers - Condition:   COVID 19 Vaccine
  Intervention:   Biological: BCG vaccine
  Sponsors:   Universidade Federal do Rio de Janeiro;   Ministry of Science and Technology, Brazil
  Recruiting

• At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19 - Condition:   Covid19
  Intervention:   Drug: bamlanivimab
  Sponsors:   Daniel Griffin, MD PhD;   Eli Lilly and Company;   Optum, Inc.
  Not yet recruiting

• Changes in Viral Load in COVID-19 After Probiotics - Condition:   COVID-19
  Intervention:   Dietary Supplement: Dietary supplementation with probiotic GASTEEL PLUS in patients with covid disease admitted to hospital
  Sponsors:   Hospital de Sagunto;   Biopolis S.L.;   Laboratorios Heel España
  Recruiting

• Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19) - Condition:   COVID-19
  Interventions:   Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment
  Sponsor:   Xi'an International Medical Center Hospital
  Active, not recruiting

• IFN-beta 1b and Remdesivir for COVID19 - Condition:   Covid19
  Interventions:   Drug: Interferon beta-1b;   Drug: Remdesivir
  Sponsor:   The University of Hong Kong
  Recruiting

• COVID-19 And Geko Evaluation: The CAGE Study - Condition:   Covid19
  Intervention:   Device: geko T3
  Sponsor:   Lawson Health Research Institute
  Not yet recruiting

• A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection - Condition:   Covid19
  Intervention:   Biological: AT-100
  Sponsor:   Airway Therapeutics, Inc.
  Not yet recruiting

• LYT-100 in Post-acute COVID-19 Respiratory Disease - Condition:   Covid19
  Interventions:   Drug: LYT-100;   Other: Placebo
  Sponsors:   PureTech;   Clinipace Worldwide;   Novotech (Australia) Pty Limited
  Not yet recruiting

• Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids - - Condition:   COVID-19
  Interventions:   Drug: Omegaven®;   Drug: Sodium chloride
  Sponsor:   Karolinska University Hospital
  Recruiting

• WHO COVID-19 Solidarity Trial for COVID-19 Treatments - Condition:   Covid19
  Interventions:   Drug: Remdesivir;   Drug: Acalabrutinib;   Drug: Interferon beta-1a;   Other: Standard of Care
  Sponsor:   The University of The West Indies
  Not yet recruiting

• COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis - Condition:   Covid19
  Interventions:   Drug: Apixaban 2.5 MG;   Drug: Placebo
  Sponsors:   Thomas Ortel, M.D., Ph.D.;   National Heart, Lung, and Blood Institute (NHLBI)
  Not yet recruiting

• Mushroom-based Product for COVID-19 - Condition:   COVID-19
  Intervention:   Drug: FoTv
  Sponsors:   Gordon Saxe;   University of California, Los Angeles;   University of California, Irvine
  Recruiting

From PubMed

• Candidate Binding Sites for Allosteric Inhibition of the SARS-CoV-2 Main Protease from the Analysis of Large-Scale Molecular Dynamics Simulations - We analyzed a 100 μs MD trajectory of the SARS-CoV-2 main protease by a non-parametric data analysis approach which allows characterizing a free energy landscape as a simultaneous function of hundreds of variables. We identified several conformations that, when visited by the dynamics, are stable for several hundred nanoseconds. We explicitly characterize and describe these metastable states. In some of these configurations, the catalytic dyad is less accessible. Stabilizing them by a suitable...

• Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha/-beta inhibitor chelerythrine -possible therapeutic implication - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. Until now, diverse drugs have been used for the treatment of COVID-19. These drugs are associated with severe side effects, e.g. induction of erythrocyte death, named eryptosis. This massively affects the oxygen (O(2)) supply of the organism. Therefore, three elementary aspects should be considered simultaneously: (1) a potential drug should directly attack the virus, (2) eliminate virus-infected host cells and (3)...

• First Report of Tocilizumab Use in a Cohort of Latin American Patients Hospitalized for Severe COVID-19 Pneumonia - Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8...

• Repurposing Known Drugs as Covalent and Non-covalent Inhibitors of the SARS-CoV-2 Papain-Like Protease - In the absence of an approved vaccine, developing effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals is essential to tackle the current pandemic health crisis due to the coronavirus disease 2019 (COVID-19) spread. As any traditional drug discovery program is a time-consuming and costly process requiring more than one decade to be completed, in silico repurposing of existing drugs is the preferred way for rapidly selecting promising clinical candidates. We present a...

• Proton pump inhibitors and the risk of severe COVID-19: a post-hoc analysis from the Korean nationwide cohort - No abstract

• Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies - CONCLUSION: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.

• Natural Products Homoharringtonine and Emetine Alkaloids for SARSCoV-2 Treatment Options - CONCLUSION: This review specifically focuses on the recent findings of these alkaloids against coronaviruses and possible treatment options for SARS-CoV-2. It is expected that natural products as alkaloids from herbal plants could be considered as novel and valuable candidates for the new antiviral drugs against SARS-CoV-2.

• Protease-activated receptor 1 as a potential therapeutic target for COVID-19 - Acute respiratory disease caused by a novel coronavirus (SARS-CoV-2) has spread all over the world, since its discovery in 2019, Wuhan, China. This disease is called COVID-19 and already killed over 1 million people worldwide. The clinical symptoms include fever, dry cough, dyspnea, headache, dizziness, generalized weakness, vomiting, and diarrhea. Unfortunately, so far, there is no validated vaccine, and its management consists mainly of supportive care. Venous thrombosis and pulmonary embolism...

• Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus belonging to the Coronavirus family, is now known to cause Coronavirus Disease (Covid-19) which was first recognized in December 2019. Covid-19 leads to respiratory illnesses ranging from mild infections to pneumonia and lung failure. Strikingly, within a few months of its first report, Covid-19 has spread worldwide at an exceptionally high speed and it has caused enormous human casualties. As yet, there is no specific...

• Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models - The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation...

• Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures - The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding of coronavirus biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects of virus replication and to serve as leads for antiviral therapeutic development. The RNA-biased amiloride scaffold was recently tuned to target a viral RNA structure critical for translation in enterovirus 71, ultimately uncovering a novel mechanism to modulate positive-sense...

• Ca (2+) -dependent mechanism of membrane insertion and destabilization by the SARS-CoV-2 fusion peptide - Cell penetration after recognition of the SARS-CoV-2 virus by the ACE2 receptor, and the fusion of its viral envelope membrane with cellular membranes, are the early steps of infectivity. A region of the Spike protein (S) of the virus, identified as the "fusion peptide" (FP), is liberated at its N-terminal site by a specific cleavage occurring in concert with the interaction of the receptor binding domain of the Spike. Studies have shown that penetration is enhanced by the required binding of Ca...

• Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms - SARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola virus and demonstrated activity against SARS-CoV-2 in vivo . Most notably the RNA polymerase targeting...

• A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections - Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N1), HIV-1, and...

• Emerging role of artificial intelligence in therapeutics for COVID-19: a systematic review - To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and pre-print original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug...

From Patent Search

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex.

• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.

• 疫苗融合蛋白 - 本申请涉及一种融合蛋白，所述融合蛋白包括SARS‑CoV‑2抗原多肽和鞭毛蛋白或其片段。本申请还提供了所述融合蛋白的制备方法和用途。本申请所述的融合蛋白能够诱导机体产生针对SARS‑CoV类病毒的抗原的细胞免疫反应。

• AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19 -

• 一种SARS-CoV-2假病毒小鼠体内包装系统及其制备方法 - 本发明提供了一种假病毒小鼠体内包装系统的制备方法，包括以下步骤：S1基于慢病毒包装质粒系统和睡美人转座子系统构建SARS‑CoV‑2假病毒包装质粒系统，S2将步骤S1中SARS‑CoV‑2假病毒包装质粒系统与睡美人转座酶表达质粒混合通过水动力注射的方式转染小鼠肝细胞，然后睡美人转座子系统将SARS‑CoV‑2假病毒包装所需序列以剪切粘贴的方式整合到小鼠肝细胞的基因组。本发明可在小鼠体内持续制造分泌SARS‑CoV‑2假病毒，可模拟靶器官被SARS‑CoV‑2病毒持续侵入攻击的过程，从而可模拟出新冠肺炎（COVID‑19）的病理特征。基于SARS‑CoV‑2假病毒小鼠体内包装系统的动物模型安全性高，不需要P3级实验室就能开展研究。利用水动力注射的方式引入SARS‑CoV‑2假病毒包装质粒系统操作简单，成本低。

• 柴胡解毒药物组合物及其制备方法和应用 - 本发明属于中药领域，具体涉及一种柴胡解毒药物组合物及其制备方法和应用，所述柴胡解毒药物组合物以质量份计由如下原料组分制成：柴胡30_{60份，黄芩15}30份，法半夏15_{30份，生姜15}30份，大枣5_{10份，枳实20}40份，大黄10_{20份，桃仁10}20份，白芍15~30份。本发明的柴胡解毒药物组合物能够显著改善普通型COVID‑19引起的咳嗽；能改善疫毒闭肺型重型COVID‑19引起的咳嗽，显著改善疫毒闭肺型重型COVID‑19引起的胸闷、气短和乏力等主要症状。另外经大量临床观察，本发明的柴胡解毒药物组合物能够显著改善疫毒闭肺型重型COVID‑19引起的发热面红，咳嗽，痰黄粘少，或痰中带血，喘憋气促，疲乏倦怠，口干苦粘，大便不畅，小便短赤等症状。

• 一种新型冠状病毒RBD核苷酸序列、优化方法与应用 - 本发明公开了一种新型冠状病毒RBD核苷酸序列、优化方法与应用。属于基因工程技术领域。优化步骤：（1）对野生型新型冠状病毒RBD核苷酸序列进行初步优化；（2）将宿主细胞特异性高表达分泌蛋白信号肽序列进行优化；（3）将人IgG1‑Fc核苷酸序列进行优化；（4）将步骤（2）优化后的宿主细胞特异性高表达分泌蛋白信号肽核苷酸序列、步骤（1）得到的初步优化新型冠状病毒RBD核苷酸序列、连接子核苷酸序列和步骤（3）优化后的人IgG1‑Fc核苷酸序列依次连接即可。与现有技术相比，本发明的有益效果：产生的克隆表达效率比野生新型冠状病毒RBD序列提高了约12倍，比中国仓鼠密码子偏性优化序列克隆表达效率提高了2倍。

• ASSISTING COMPLEX FOR TAKING OF BIOMATERIAL FROM MOUTH IN PANDEMIC CONDITIONS - FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to methods for contactless taking of biomaterial in tested person. Taking the biomaterial in the tested person is carried out in a room located in a dirty zone and separated by a partition from the clean zone, in which there is a laboratory assistant performing the procedure using a robotic complex. Complex includes digital controller, manipulator with tool unit, small manipulator, camera, monitor, control system of digital controller, manipulator, small manipulator, and complex control system. In the partition there are two holes: one – for installation and passage of the swab, the other – for the test tube installation. In the dirty zone there is a small manipulator having two actuators: one for movement of a test tube with a swab, and the second for positioning and placing a disposable mouthpiece. EFFECT: reduced risk of laboratory assistant and tested person infection by avoiding their direct contact. 17 cl, 1 dwg

• Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -

  Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.

• Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -

  Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.