Covid-19 Sentry

Contents

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

From Preprints

• SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe -

  People with pre-existing chronic health conditions are reportedly at high risk of getting the coronavirus disease (COVID-19) and of having a severe disease course but little data exist on rare diseases such as Primary Ciliary Dyskinesia (PCD). We studied risk and severity of SARS-CoV-2 infections among people with PCD using data from the COVID-PCD, a participatory study that collects data in real-time directly from people with PCD. Data was collected using online questionnaires. A baseline questionnaire collected information on demographic data, information about the PCD diagnosis and severity. A short weekly questionnaire collected information about current symptoms and incident SARS-CoV-2 infections. 578 people participated in the COVID-PCD by December 7, 2020, with a median number of follow-up weeks of 9 (interquartile range: 4-19 weeks). 256 (45%) of the participants had been tested for SARS-CoV-2 and 12 tested positive prior to study entry or during study follow up (2.1% of the total included population, 95% confidence interval (CI) 1.1-3.6%). 4 people tested positive during the study follow-up, corresponding to an incidence rate of 2.5 per 100 person-years (95% CI: 0.9-6.5). Overall, reported severity was mild with two reporting no symptoms, eight reporting mild symptoms, one reporting severe symptom without hospitalisation, and one reporting hospitalisation for 9 days. The study suggests that with careful personal protection, people with PCD do not seem to have an increased risk of infection with SARS-COV-2, nor an especially severe disease course.

  🖺 Full Text HTML: SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe
• Defective NETs Clearance contributes to sustained FXII Activation in COVID-19-associated Pulmonary Thrombo-Inflammation -
  Coagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) and are associated with increased mortality. The mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. Here, we report a role of the NETs/ Factor XII (FXII) axis for initiating procoagulant and proinflammatory reactions in COVID-19. Proteomic analysis revealed enrichment of FXII in postmortem lung tissue from COVID-19 patients. Immunofluorescence analysis of COVID-19 lung tissue showed that FXII is activated in the lung parenchyma, within the pulmonary vessel walls and in fibrin-rich alveolar spaces. In particular, activated FXII (FXIIa) colocalized with NETs in COVID-19 lung tissue, indicating that NETs accumulation leads to FXII contact activation in COVID-19. We further showed that an accumulation of NETs is partially caused by impaired NETs clearance via extracellular DNases. In contrast, addition of DNase I improved NETs clearance and reduced FXII activation in vitro. We propose that targeting both, FXIIa and the FXII activator NETs, is therapeutically effective in mitigating thrombo-inflammation in COVID-19.
  🖺 Full Text HTML: Defective NETs Clearance contributes to sustained FXII Activation in COVID-19-associated Pulmonary Thrombo-Inflammation
• Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence -
  Passive immunisation using monoclonal antibodies will play a vital role in the fight against COVID-19. Until now, the majority of anti-SARS-CoV-2 antibody discovery efforts have relied on screening B cells of patients in the convalescent phase. Here, we describe deep-mining of the antibody repertoires of hospitalised COVID-19 patients using a combination of phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralising antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded potent neutralising antibodies with distinct mechanisms of action, including the identification of a novel non-ACE2 receptor blocking antibody that is not expected to be affected by any of the major viral variants reported. The study highlighted the presence of potent neutralising antibodies with near germline sequences within both the IgG and IgM pools at early stages of infection. Furthermore, we highlight a highly convergent antibody response with the same sequences occurring both within this study group and also within the responses described in previously published anti-SARS-CoV-2 studies.
  🖺 Full Text HTML: Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence
• Paired SARS CoV-2 Spike Protein Mutations Observed During Ongoing SARS-CoV-2 Viral Transfer from Humans to Minks and Back to Humans -
  A mutation analysis of a collection of SARS-CoV-2 genomes around the world via sequence, date, geographic location, and species has revealed a large number of variants from the initial reference sequence in Wuhan. It also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations often in combination, in the spike protein receptor binding domain (RBD) has apparently transferred back into humans. The viral genomic mutations in minks observed in the Netherlands and Denmark show the potential for new mutations on the SARS-CoV-2 spike protein RBD to be introduced into humans by zoonotic transfer. Our data suggests that close attention to viral transfer from humans to farm animals and pets will be required to prevent build-up of a viral reservoir for future zoonotic transfer.
  🖺 Full Text HTML: Paired SARS CoV-2 Spike Protein Mutations Observed During Ongoing SARS-CoV-2 Viral Transfer from Humans to Minks and Back to Humans
• Neutralising antibodies drive Spike mediated SARS-CoV-2 evasion -

  SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2, and amino acid variation in Spike is increasingly appreciated. Given both vaccines and therapeutics are designed around Wuhan-1 Spike, this raises the theoretical possibility of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days. Although little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days, N501Y in Spike was transiently detected at day 55 and V157L in RdRp emerged. However, following convalescent plasma we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and 𝚫H69/𝚫V70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing 𝚫H69/𝚫V70 and D796H conferred decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility, but incurred an infectivity defect. The 𝚫H69/𝚫V70 single mutant had two-fold higher infectivity compared to wild type and appeared to compensate for the reduced infectivity of D796H. Consistent with the observed mutations being outside the RBD, monoclonal antibodies targeting the RBD were not impacted by either or both mutations, but a non RBD binding monoclonal antibody was less potent against 𝚫H69/𝚫V70 and the double mutant. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with reduced susceptibility to neutralising antibodies.

  🖺 Full Text HTML: Neutralising antibodies drive Spike mediated SARS-CoV-2 evasion
• The effective reproductive number (Rt) of COVID-19 and its relationship with social distancing -

  The expansion of the new coronavirus disease (COVID-19) triggered a renewed public interest in epidemiological models and on how parameters can be estimated from observed data. Here we investigated the relationship between average number of transmissions though time, the reproductive number Rt, and social distancing index as reported by mobile phone data service inloco, for Goias State, Brazil, between March and June 2020. We calculated Rt values using EpiEstim package in R-plataform for confirmed cases incidence curves. We found a correlation equal to -0.72 between Rt values for confirmed cases and isolation index at a time lag of 8 days. As the Rt values were paired with center of the moving window of 7 days, the delay matches the mean incubation period of the virus. Our findings reinforce that isolation index can be an effective surrogate for modeling and epidemiological analyses and, more importantly, can be an useful metrics for anticipating the need for early interventions, a critical issue in public health.

  🖺 Full Text HTML: The effective reproductive number (Rt) of COVID-19 and its relationship with social distancing
• Epitopes targeted by T cells in convalescent COVID-19 patients -
  Knowledge of the epitopes of SARS-CoV-2 that are targeted by T cells in convalescent patients is important for understanding T cell immunity against COVID-19. This information can aid the design, development and assessment of COVID-19 vaccines, and inform novel diagnostic technologies. Here we provide a unified description and meta-analysis of emerging data of SARS-CoV-2 T cell epitopes compiled from 15 independent studies of cohorts of convalescent COVID-19 patients. Our analysis demonstrates the broad diversity of T cell epitopes that have been collectively recorded for SARS-CoV-2, while also identifying a selected set of immunoprevalent epitopes that induced consistent T cell responses in multiple cohorts and in a large fraction of tested patients. The landscape of SARS-CoV-2 T cell epitopes that we describe can help guide future immunological studies, including those related to vaccines and diagnostics. A web-based platform has been developed to help complement these efforts.
  🖺 Full Text HTML: Epitopes targeted by T cells in convalescent COVID-19 patients
• Information concerning others more than individual variables modulates interpersonal distance in the times of COVID-19 pandemic: a bayesian analysis approach -
  Creating and maintaining bonds in humans typically comes with interactions occurring at close social distances which are usually shorter than the one (of at least 1.5 meters) recommended as a relevant measure of COVID-19 contagion containment. In a web-based experimental study conducted during the first pandemic wave (mid-April 2020), we asked 242 participants to regulate their preferred distance towards confederates who did or did not wear protective mask/gloves and who could have tested positive or negative to COVID-19 or whose test results are unknown. Information concerning the dispositional factors (perceived vulnerability to disease, moral attitudes and prosocial tendencies) and situational factors (perceived severity of the situation in the country, frequency of physical and virtual social contacts and attitudes toward quarantine) that may modulate compliance with safety prescriptions was also acquired. A bayesian analysis approach was adopted. Individual differences did not modulate the interpersonal distance. We found strong evidence in favor of a reduction of interpersonal distance towards characters wearing protective equipment and who tested negative to Covid-19. Importantly, shorter interpersonal distances were kept towards confederates wearing protections, even when their test result was unknown or turned out positive to Covid-19. The protective equipment-related regulation of interpersonal distance may reflect an underestimation of the perceived vulnerability to the infection, which has to be discouraged when pursuing individual and collective safety.
  🖺 Full Text HTML: Information concerning others more than individual variables modulates interpersonal distance in the times of COVID-19 pandemic: a bayesian analysis approach
• REBIRTH Epistemological Paradigm as a transformational tool for individuals and organizations post COVID-19 outbreak: a new normal adaptation model -
  COVID-19 has impacted how organisations function the world over. Adaptation models that will bring sustainability in the new normal will need to integrate humanistic perspectives beyond the five normal dimensions of emotional intelligence to inculcating the cultural perspectives and indegenous methods of community engagement and inquiry. This article is one of a series produced by authors, pursuant to an intense doctoral study by one of the authors which culminated in a Rebirth model. The setting of the study was at one of the largest banking groups in South Africa, whereby collective engagement for Organisational Change and Development (OCD) using multiple methods within the intepretivist ontological phylosophy was investigated. The study resulted in the establishment of Rebirth first as a paradigm for enquiry, complemented by phenomenological research strategy in conjuction with the Integral Research Approach (IRA) using both Feminist Transformative theories in a Participatory Action Research (PAR) mode for data collection. This paper provides basic steps into undertanding Rebirth philosophy through explication of its six (6) pillars, namely; Ubuntu-Botho, Nature, Dialogue, Story-telling, Symbols and Tribal Circle. Core to the Rebirth philosophy are the eight (8) human factors of behavior, classified as quotients in a spiral direction representing the womb as a place of seed germination to birth and ultimate attainment of knoledge that leads to productive execution.
  🖺 Full Text HTML: REBIRTH Epistemological Paradigm as a transformational tool for individuals and organizations post COVID-19 outbreak: a new normal adaptation model
• Containing the Spread of Infectious Disease on College Campuses -

  College campuses are highly vulnerable to infectious diseases outbreaks, and there is a mounting need to develop strategies that best mitigate their size and duration, particularly as colleges consider reopening their campuses in the midst of the COVID-19 pandemic. Towards addressing this need, we applied a stochastic transmission model to quantify the impact of university-level responses to past outbreaks on their campuses and used it to determine which control interventions are most effective. The model aims to simultaneously overcome three crucial issues: stochastic variation in small populations, missing or unobserved case data, and changes in disease transmission rates post-intervention. We tested the model and assessed various interventions using data from the 2014 and 2016 mumps outbreaks at Ohio State University and Harvard University, respectively. Our results suggest that universities should design more aggressive diagnostic procedures and stricter isolation policies to decrease infectious disease incidence on campus. Our model can be applied to data from other outbreaks in college campuses and similar small- population settings.

  🖺 Full Text HTML: Containing the Spread of Infectious Disease on College Campuses
• Propensity to reappraise promotes resilience to stress-induced negativity bias -
  Stress exposure is associated with an increased tendency to appraise ambiguous social stimuli as negative. However, it remains unknown whether tendencies to use emotion regulation strategies—such as cognitive reappraisal, which involves altering the meaning of affective stimuli—can buffer these stress effects on social evaluations. Here, we examined whether increased reappraisal use confers resilience against stress-induced negativity bias. In Study 1, healthy participants (n=43) rated the valence of emotionally ambiguous (surprised) faces before and after an acute stress or control manipulation and reported reappraisal habits. Increased negativity ratings were milder for stressed individuals that reported more habitual reappraisal use. In Study 2 (n=97), we extended this investigation to real-world perceived stress before and during the COVID-19 pandemic. We found that reappraisal tendency moderates the relationship between perceived stress and increased negativity bias. Collectively, these findings suggest that the propensity to reappraise attenuates stress-induced negativity bias when evaluating others under uncertainty.
  🖺 Full Text HTML: Propensity to reappraise promotes resilience to stress-induced negativity bias
• Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond? -
  Definitive antiviral properties are evidenced for niacin, i.e., nicotinic acid (NA), as coronavirus disease 2019 (COVID-19) therapy for both disease recovery and prevention, to the level that reversal or progression of its pathology follows as an intrinsic function of NA supply. This detailed investigation provides a thorough disentanglement of how the downstream inflammatory propagation of ensuing severe acute respiratory virus 2 (SARS-CoV-2) infection is entirely prohibited or reversed upstream out the body to expeditiously restore health with well-tolerated dynamic supplementation of sufficient NA (i.e., ~1-3 grams per day). Culmination of this research leads to realization of the potentially ubiquitous therapeutic and preventive powers of NA against inflammatory disease, in general.
  🖺 Full Text HTML: Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond?
• The COVID-19 Pandemic’s Impact on OCD Symptoms Varies Widely -
  We conducted a survey of adults with OCD during COVID-19, but found a much higher rate of OCD symptom worsening than similar studies did. Here, we describe our study and discuss potential reasons for these differing patterns of results.
  🖺 Full Text HTML: The COVID-19 Pandemic’s Impact on OCD Symptoms Varies Widely
• An Ultrasensitive Biosensor for Quantifying the Interaction of SARS-CoV-2 and Its Receptor ACE2 in Cells and in vitro -
  The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus-host interaction in order to quickly evaluate infectious ability of mutant virus and develop or validate virus-inhibiting drugs. Here we have developed an ultrasensitive bioluminescent biosensor to evaluate virus-cell interaction by quantifying the interaction between SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants, and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid and HTP biosensor tool will significantly expedite detection of viral mutants and anti-COVID-19 drug discovery processes.
  🖺 Full Text HTML: An Ultrasensitive Biosensor for Quantifying the Interaction of SARS-CoV-2 and Its Receptor ACE2 in Cells and in vitro
• Rapid expression of COVID-19 proteins by transient expression in tobacco. -
  In 2020 we suffered from a major global pandemic caused by the SARS-CoV-2 coronavirus. Efforts to contain the virus include the development of rapid tests and vaccines, which require a ready supply of viral proteins. Here we report the production of two SARS-CoV-2 proteins by transient transformation of tobacco, leading to high expression within three days, and subsequent purification of the intact proteins. Such efforts may help to develop testing resources to alleviate the major impacts of this global pandemic.
  🖺 Full Text HTML: Rapid expression of COVID-19 proteins by transient expression in tobacco.

From Clinical Trials

• Dendritic Cell Vaccine to Prevent COVID-19 - Condition:   COVID-19
  Intervention:   Biological: AV-COVID-19
  Sponsors:   Indonesia-MoH;   Aivita Biomedical, Inc.;   PT AIVITA Biomedika Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia;   RSUP Dr. Kariadi Semarang, indonesia;   Faculty of Medicine University of Diponegoro, Indonesia
  Recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in 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, SCIENCE AND APPLIED TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• Inhaled Ivermectin and COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Ivermectin Powder
  Sponsor:   Mansoura University
  Not yet recruiting

• AZD1222 Vaccine in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   AstraZeneca;   R-Pharm
  Not yet recruiting

• Study in Adults to Determine the Safety and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, Given in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19. - Condition:   COVID-19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   R-Pharm;   AstraZeneca
  Not yet recruiting

• Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Colchicine;   Drug: Standard COVID-19 care
  Sponsors:   Ayub Teaching Hospital;   Universidad de Murcia
  Recruiting

• Dendritic Cell Vaccine, AV-COVID-19, to Prevent COVID-19 Infection - Condition:   COVID-19
  Interventions:   Biological: AV-COVID-19;   Other: GM-CSF
  Sponsors:   Aivita Biomedical, Inc.;   PT AIVITA Biomedika Indonesia;   Indonesia Ministry of Health;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
  Recruiting

• Efficacy and Safety of hzVSF-v13 in Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Interventions:   Drug: hzVSF-v13;   Drug: Placebo (Normal saline solution)
  Sponsor:   ImmuneMed, Inc.
  Recruiting

• Efficacy and Safety of hzVSFv13 in Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Interventions:   Drug: hzVSF-v13;   Drug: Placebo (Normal saline solution)
  Sponsor:   ImmuneMed, Inc.
  Not yet recruiting

• Efficacy and Safety of hzVSF-v13 in Moderate to Severe Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Interventions:   Drug: hzVSF-v13;   Drug: Placebo (Normal saline solution)
  Sponsor:   ImmuneMed, Inc.
  Not yet recruiting

• A Controlled Phase 2/3 Study of Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Vaccine (SCB-2019) for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AS03-adjuvanted SCB-2019 vaccine;   Biological: Placebo; 0.9% saline
  Sponsors:   Clover Biopharmaceuticals AUS Pty Ltd;   The Coalition for Epidemic Preparedness Innovations;   International Vaccine Institute
  Not yet recruiting

• Evaluation of the Efficacy of High Doses of Methylprednisolone in SARS-CoV2 ( COVID-19) Pneumonia Patients - Condition:   Covid19
  Intervention:   Drug: Methylprednisolone, Placebo
  Sponsor:   Azienda Unità Sanitaria Locale Reggio Emilia
  Not yet recruiting

• Risk of Infection of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), COVID-19, in a Massive Musical Show With Transmission Prevention Measures - Condition:   COVID-19 (SARS-CoV-2)
  Intervention:   Behavioral: Participate in a massive musical event
  Sponsors:   Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia;   Dr. Bonaventura Clotet Sala;   Dr. Josep Mª LLibre Codina;   Dr. Boris Revollo Barriga;   Dra. Lidia Ruiz Tabuenca;   Dr. Ignacio Blanco Guillermo;   Dra. Andrea Alemany Ortiz;   Dr. Roger Paredes Deiros
  Active, not recruiting

• Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Hydroxychloroquine;   Behavioral: personal protective Measures
  Sponsor:   Benha University
  Completed

• Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19 - Condition:   Covid19
  Interventions:   Drug: Dalcetrapib;   Other: Placebo
  Sponsors:   DalCor Pharmaceuticals;   The Montreal Health Innovations Coordinating Center (MHICC);   Covance
  Not yet recruiting

From PubMed

• Conus venom fractions inhibit the adhesion of Plasmodium falciparum erythrocyte membrane protein 1 domains to the host vascular receptors - Using high-throughput BioPlex assays, we determined that six fractions from the venom of Conus nux inhibit the adhesion of various recombinant PfEMP-1 protein domains (PF08_0106 CIDR1α3.1, PF11_0521 DBL2β3, and PFL0030c DBL3X and DBL5e) to their corresponding receptors (CD36, ICAM-1, and CSA, respectively). The protein domain-receptor interactions permit P. falciparum-infected erythrocytes (IE) to evade elimination in the spleen by adhering to the microvasculature in various organs including the...

• Uncovering Flexible Active Site Conformations of SARS-CoV-2 3CL Proteases through Protease Pharmacophore Clusters and COVID-19 Drug Repurposing - The infectious SARS-CoV-2 causes COVID-19, which is now a global pandemic. Aiming for effective treatments, we focused on the key drug target, the viral 3C-like (3CL) protease. We modeled a big dataset with 42 SARS-CoV-2 3CL protease-ligand complex structures from ∼98.7% similar SARS-CoV 3CL protease with abundant complex structures. The diverse flexible active site conformations identified in the dataset were clustered into six protease pharmacophore clusters (PPCs). For the PPCs with distinct...

• In silico analysis of phytochemicals as potential inhibitors of proteases involved in SARS-CoV-2 infection - In silico analysis of six phytochemicals, flabelliferin, marmelosin, piperine, ocimin, curcumin and leucoanthocyanin, along with three drug compounds, nelfinavir, remdesivir and hydroxychloroquine, as positive control against drug targets of one SARS-CoV-2 viral protease, COVID-19 main protease (SARS CoV-2 3CL^(pro)/M(pro)), two coronavirus proteases, SARS-CoV main peptidase (SARS CoV M^(pro)), SARS-CoV main proteinase (SARS CoV 3CL^(pro)), and one human cellular transmembrane serine proteinase...

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread worldwide and has affected more than 10 million individuals. A typical feature of COVID-19 is the suppression of type I and III interferon (IFN)-mediated antiviral immunity. However, the molecular mechanism by which SARS-CoV-2 evades antiviral immunity remains elusive. Here, we reported that the SARS-CoV-2 membrane (M) protein inhibits the production of type I and III...

• The potential mechanism of N-acetylcysteine in treating COVID-19 - N-Acetylcysteine (NAC) has been proposed and used to treat coronavirus disease 2019 (COVID-19). By reviewing the existing pathological studies of COVID-19, it was found that abundant mucus secretion, formation of a hyaline membrane (supportive of acute respiratory distress syndrome), and interstitial fibrous exudation may be important characteristics of COVID-19 and may be pathological targets of drug therapy. In addition, multiple extrapulmonary organ injuries in COVID-19 may be associated with...

• The fight against human viruses: how NMR can help - CONCLUSION: Considering the NMR-based work conducted on different viruses, we believe that in the close future much more NMR efforts will be devoted to discover novel anti SARS-CoV-2 agents.

• A Review of Treatment of Coronavirus Disease 2019 (COVID-19): Therapeutic Repurposing and Unmet Clinical Needs - For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that in vitro inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of...

• Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: signifying strong drug-drug interactions - Remdesivir was recently approved to treat COVID-19. While this antiviral agent delivers clinical benefits, several safety concerns in many cases have been raised. This study reports that remdesivir at nanomolar concentrations inhibits carboxylesterase-2 (CES2) through covalent modifications. CES2 is a major drug-metabolizing enzyme. The combination of high potency with irreversible inhibition concludes that cautions must be exercised when remdesivir is used along with drugs hydrolyzed by CES2.

• Might proton pump or sodium-hydrogen exchanger inhibitors be of value to ameliorate SARs-CoV-2 pathophysiology? - Discovering therapeutics for COVID-19 is a priority. Besides high-throughput screening of compounds, candidates might be identified based on their known mechanisms of action and current understanding of the SARs-CoV-2 life cycle. Using this approach, proton pump (PPIs) and sodium-hydrogen exchanger inhibitors (NHEIs) emerged, because of their potential to inhibit the release of extracellular vesicles (EVs; exosomes and/or microvesicles) that could promote disease progression, and to directly...

• Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS-CoV-2 in the respiratory tract - As the death toll of Coronavirus disease 19 (COVID-19) continues to rise worldwide, it is imperative to explore novel molecular mechanisms for targeting SARS-CoV-2. Rather than looking for drugs that directly interact with key viral proteins inhibiting its replication, an alternative and possibly add-on approach is to dismantle the host cell machinery that enables the virus to infect the host cell and spread from one cell to another. Excellent examples of such machinery are host cell proteases...

• Spatial and temporal roles of SARS-CoV PL(pro) -A snapshot - SARS-CoV and SARS-CoV-2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C-like cysteine protease (3CL^(pro) ) and papain-like protease (PL^(pro) ) into 16 nonstructural proteins (nsps). PL^(pro) is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2, between nsp2/3 and between nsp3/4 with recognition motif of LXGG, and the sites in...

• Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin - The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here,...

• Therapeutic Approach Against 2019-nCoV by Inhibition of the ACE-2 receptor - The continued spread of the 2019 novel coronavirus (2019-nCoV) has prompted global concern. The formal name given to 2019-nCoV by the World Health Organization is COVID-19, while the International Committee on Taxonomy has named it severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to this viral attack, nations around the world have issued lockdown restrictions. Presently, there is no effective way to control the spread of 2019-nCoV, except through social distancing and hygienic...

• Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic - Neutrophil extracellular traps (NETs) contribute to immunothrombosis and have been associated with mortality in Coronavirus Disease 2019 (COVID-19). We stimulated donor neutrophils with plasma from patients with COVID-19 and demonstrate that R406 can abrogate the release of NETs. These data provide evidence for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.

• Identification of Small Molecule Inhibitors of the Deubiquitinating Activity of the SARS-CoV-2 Papain-Like Protease: in silico Molecular Docking Studies and in vitro Enzymatic Activity Assay - COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 virus with important political, socio-economic, and public health consequences. Inhibiting replication represents an important antiviral approach, and in this context two viral proteases, the SARS-CoV-2 main and papain-like proteases (PL^(pro)), which cleave pp1a and pp1ab polypeptides, are critical. Along with protease activity, the PL^(pro) possesses deubiquitinating activity, which is important in immune regulation. Naphthalene-based...

From Patent Search

• Covid 19 - Chewing Gum - - link

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• "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. - link

• 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물 - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염; 및 글루카곤 수용체 작용제(glucagon receptor agonist), 위 억제 펩타이드(gastric inhibitory peptide, GIP), 글루카곤-유사 펩타이드 1(glucagon-like peptide 1, GLP-1) 및 글루카곤 수용체/위 억제 펩타이드/글루카곤-유사 펩타이드 1(Glucagon/GIP/GLP-1) 삼중 완전 작용제(glucagon receptors, gastric inhibitory peptide and glucagon-like peptide 1 (Glucagon/GIP/GLP-1) triple full agonist)로 이루어진 군으로부터 선택된 1종 이상;을 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. - link

• 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. - link

• SARS-CoV-2 RBD共轭纳米颗粒疫苗 - 本发明涉及免疫医学领域，具体而言，涉及一种SARS‑CoV‑2 RBD共轭纳米颗粒疫苗。该疫苗包含免疫原性复合物，所述免疫原性复合物包含：a）与SpyCatcher融合表达的载体蛋白自组装得到的纳米颗粒载体；b）与SpyTag融合表达的SARS‑CoV‑2病毒的RBD抗原；所述载体蛋白选自Ferritin、mi3和I53‑50；所述载体蛋白与所述抗原之间通过SpyCatcher‑SpyTag共价连接。 - link

• Устройство электронного контроля и дистанционного управления аппарата искусственной вентиляции легких - Полезная модель относится к медицинской технике, а именно к устройствам для воздействия на дыхательную систему пациента смесью различных газов, в частности, к устройствам для проведения искусственной вентиляции легких (ИВЛ). Технический результат предлагаемой полезной модели заключается в решении технической проблемы, состоящей в необходимости расширения арсенала технических средств, предназначенных для электронного контроля и управления ИВЛ, путем реализации возможности дистанционного управления аппаратами ИВЛ в медицинских учреждениях, не оборудованных кабельными вычислительными сетями. Указанный технический результат достигается благодаря тому, что в известное устройство электронного контроля и дистанционного управления аппарата ИВЛ, содержащее центральный микроконтроллер, а также программно-аппаратные средства управления функциями доставки воздушной смеси пациенту и многоуровневой тревожной сигнализации об отклонениях от нормативных условий и технических неполадках в аппарате ИВЛ, введены связанные друг с другом микроконтроллер связи и дистанционного управления и радиомодем, выполненный с возможностью связи с точками доступа радиканальной сети, при этом центральный микроконтроллер устройства выполнен с дополнительными входом/выходом, которые связаны с управляющими выходом/входом микроконтроллера связи и дистанционного управления, а, в зависимости от типа применяемой в медицинском учреждении радиоканальной сети связи и передачи данных, радиомодем может быть выполнен в виде интерфейсного аудиомодуля Bluetooth 4.0 BLE, приемопередающего модуля Wi-Fi либо устройства "малого радиуса действия", работающего по технологии LoRa на нелицензируемых частотах мегагерцового диапазона, например, в диапазоне 868 МГц. 3 з.п. ф-лы, 1 ил. - link