Covid-19 Sentry

Contents

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

From Preprints

• COVID-19 experience and challenges from a referral hospital in East Borneo, Indonesia: a case series -
  Coronavirus disease 2019 (COVID-19) is a multifaceted disease and pandemic control requires a collaborative approach between various stakeholders from frontline doctors to governing bodies. Here we report the challenges faced in early COVID-19 cases that were admitted to Balikpapan General Hospital, East Borneo, Indonesia. We highlighted the insufficiencies in implementing the regulations endorsed by Indonesian Government in low resource settings.
  🖺 Full Text HTML: COVID-19 experience and challenges from a referral hospital in East Borneo, Indonesia: a case series
• Pyronaridine Protects Against SARS-CoV-2 in Mouse -
  There are currently relatively few small-molecule antiviral drugs that are either approved or emergency approved for use against SARS-CoV-2. One of these is remdesivir, which was originally repurposed from its use against Ebola and functions by causing early RNA chain termination. We used this as justification to evaluate three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg. Out of these we previously identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. Herein, the in vivo efficacy of pyronaridine has now been assessed in a K18-hACE transgenic mouse model of COVID-19. Pyronaridine treatment demonstrated a statistically significant reduction of viral load in the lungs of SARS CoV-2 infected mice. Furthermore, the pyronaridine treated group reduced lung pathology, which was also associated with significant reduction in the levels of pro-inflammatory cytokines/chemokine and cell infiltration. Notably, pyronaridine inhibited the viral PLpro activity in vitro (IC50 of 1.8 uM) without any effect on Mpro, indicating a possible molecular mechanism involved in its ability to inhibit SARS-CoV-2 replication. Interestingly, pyronaridine also selectively inhibits the host kinase CAMK1 (IC50 of 2.4 uM). We have also generated several pyronaridine analogs to assist in understanding the structure activity relationship for PLpro inhibition. Our results indicate that pyronaridine is a potential therapeutic candidate for COVID-19.
  🖺 Full Text HTML: Pyronaridine Protects Against SARS- CoV-2 in Mouse
• Ad26.COV2.S Prevents SARS-CoV-2 Induced Pathways of Inflammation and Thrombosis in Hamsters -
  Syrian golden hamsters exhibit features of severe disease after SARS-CoV-2 challenge and are therefore useful models of COVID-19 pathogenesis and prevention with vaccines. Recent studies have shown that SARS-CoV-2 infection stimulates type I interferon, myeloid, and inflammatory signatures similar to human disease, and that weight loss can be prevented with vaccines. However, the impact of vaccination on transcriptional programs associated with COVID-19 pathogenesis and protective adaptive immune responses is unknown. Here we show that SARS-CoV-2 challenge in hamsters stimulates antiviral, myeloid, and inflammatory programs as well as signatures of complement and thrombosis associated with human COVID-19. Notably, single dose immunization with Ad26.COV2.S, an adenovirus serotype 26 vector (Ad26)-based vaccine expressing a stabilized SARS-CoV-2 spike protein, prevents the upregulation of these pathways such that the gene expression profiles of vaccinated hamsters are comparable to uninfected animals. Finally, we show that Ad26.COV2.S vaccination induces T and B cell signatures that correlate with binding and neutralizing antibody responses. These data provide further insights into the mechanisms of Ad26.COV2.S based protection against severe COVID-19 in hamsters.

• SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies -
  SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from non-VOC COVID-19 patients and vaccinated individuals. Here, serum of Beta variant infected patients revealed reduced cross- neutralization of non-VOC virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of novel VOC-specific clonotypes and accommodation of VOC-defining amino acids into a major non-VOC antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with non-VOC-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge independent of VOC mutations. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics.
  🖺 Full Text HTML: SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies
• Durability of immune responses to the BNT162b2 mRNA vaccine -
  The development of the highly efficacious mRNA vaccines in less than a year since the emergence of SARS-CoV-2 represents a landmark in vaccinology. However, reports of waning vaccine efficacy, coupled with the emergence of variants of concern that are resistant to antibody neutralization, have raised concerns about the potential lack of durability of immunity to vaccination. We recently reported findings from a comprehensive analysis of innate and adaptive immune responses in 56 healthy volunteers who received two doses of the BNT162b2 vaccination. Here, we analyzed antibody responses to the homologous Wu strain as well as several variants of concern, including the emerging Mu (B.1.621) variant, and T cell responses in a subset of these volunteers at six months (day 210 post-primary vaccination) after the second dose. Our data demonstrate a substantial waning of antibody responses and T cell immunity to SARS- CoV-2 and its variants, at 6 months following the second immunization with the BNT162b2 vaccine. Notably, a significant proportion of vaccinees have neutralizing titers below the detection limit, and suggest a 3rd booster immunization might be warranted to enhance the antibody titers and T cell responses.
  🖺 Full Text HTML: Durability of immune responses to the BNT162b2 mRNA vaccine
• Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice -
  The COVID-19 pandemic dramatically demonstrated the need for improved vaccination strategies and therapeutic responses to combat infectious diseases. However, the efficacy of vaccines has not yet been demonstrated in combination with commonly used immunosuppressive drug regimens. We sought to determine how common pharmaceutical drugs used in autoimmune disorders can alter immune responses to the SARS-CoV-2 spike protein vaccination. We treated mice with five immunosuppressant drugs (cyclophosphamide, leflunomide, methotrexate, methylprednisolone, and mycophenolate mofetil), each with various mechanisms of action prior to and following immunization with SARS-CoV-2 spike protein. We assessed the functionality of antibody responses to spike protein and compared immune cell populations in mice that received no treatment with those that received continuous or temporarily suspended immune suppressive therapy. All tested immunosuppressants significantly reduced the antibody titers in serum and functional antibody response against SARS- CoV-2 spike protein in immunized mice. Temporarily halting selected immunosuppressants (methylprednisolone and methotrexate, but not cyclophosphamide) improved antibody responses significantly. Through proof-of-principle experiments utilizing a mouse model, we demonstrated that immune suppression in autoimmune disorders through pharmaceutical treatments may impair vaccine response to SARS-CoV-2, and temporary suspension of immunosuppressant treatment may be necessary to mount an effective antibody vaccine response. This work provides feasibility for future clinical assessment of the impact of immunosuppressants on vaccine efficacy in humans.
  🖺 Full Text HTML: Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice
• Face masks impair reconstruction of acoustic speech features and higher-level segmentational features in the presence of a distractor speaker -
  Face masks have become a prevalent measure during the Covid-19 pandemic to counteract the transmission of SARS-CoV

2. An unintended ‘side-effect’ of face masks is their adverse influence on speech perception especially in challenging listening situations. So far, behavioural studies have not pinpointed exactly which feature(s) of speech processing face masks affect in such listening situations. We conducted an audiovisual (AV) multi-speaker experiment using naturalistic speech (i.e. an audiobook). In half of the trials, the target speaker wore a (surgical) face mask, while we measured the brain activity of normal hearing participants via magnetoencephalography (MEG). A decoding model on the clear AV speech (i.e. no additional speaker and target speaker not wearing a face mask) was trained and used to reconstruct crucial speech features in each condition. We found significant main effects of face masks on the reconstruction of acoustic features, such as the speech envelope and spectral speech features (i.e. pitch and formant frequencies), while reconstruction of higher level features of speech segmentation (phoneme and word onsets) were especially impaired through masks in difficult listening situations, i.e. when a distracting speaker was also presented. Our findings demonstrate the detrimental impact face masks have on listening and speech perception, thus extending previous behavioural results. Supporting the idea of visual facilitation of speech is the fact that we used surgical face masks in our study, which only show mild effects on speech acoustics. This idea is in line with recent research, also by our group, showing that visual cortical regions track spectral modulations. Since hearing impairment usually affects higher frequencies, the detrimental effect of face masks might pose a particular challenge for individuals who likely need the visual information about higher frequencies (e.g. formants) to compensate.
   🖺 Full Text HTML: Face masks impair reconstruction of acoustic speech features and higher-level segmentational features in the presence of a distractor speaker

• SARS-CoV-2 Beta Variant Substitutions Alter Spike Glycoprotein Receptor Binding Domain Structure and Stability -
  The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the subsequent COVID-19 pandemic has visited a terrible cost on the world in the forms of disease, death, and economic turmoil. The rapid development and deployment of extremely effective vaccines against SARS-CoV-2 have seemingly brought within reach the end of the pandemic. However, the virus has acquired mutations; and emerging variants of concern (VOC) are more infectious and reduce the efficacy of existing vaccines. While promising efforts to combat these variants are underway, the evolutionary pressures leading to these variants are poorly understood. To that end, here we have studied the effects on the structure and function of the SARS-CoV-2 spike glycoprotein receptor-binding domain of three amino-acid substitutions found in several variants of concern, including alpha (B.1.1.7), beta (B.1.351), and gamma (P.1). We found that these substitutions alter the RBD structure, stability, and ability to bind to ACE2, in such a way as to possibly have opposing and compensatory effects. These findings provide new insights into how these VOC may have been selected for infectivity while maintaining the structure and stability of the receptor binding domain.
  🖺 Full Text HTML: SARS-CoV-2 Beta Variant Substitutions Alter Spike Glycoprotein Receptor Binding Domain Structure and Stability
• SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before the Delta surge, March-June 2021 -

  In a representative serosurvey conducted March-June 2021, 64.1% (95%CrI 60.0-68.1%) of Sitakunda subdistrict (Bangladesh) had anti-SARS-CoV-2 IgG antibodies after adjusting for age, sex, household clustering and test performance. Before the surge of Delta, most of the population had been infected despite low incidence of virologically-confirmed COVID-19.

  🖺 Full Text HTML: SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before the Delta surge, March-June 2021
• Security motives and personal well-being during the early months of the COVID-19 pandemic -
  Objective: Past research suggests that having a stronger ability to regulate feelings and behaviors can help individuals cope during stressful events, but little is known about why and when this might be the case. We examined if being more focused on prevention (i.e., health security motives) impacted personal well-being during the COVID-19 pandemic. We also examined possible underlying mechanisms for this effect, and whether perceived social support buffered it. Design: We conducted a pre-registered longitudinal study over one month (N = 1,269). Main outcome measures: Regulatory focus, worry for health (T1), adherence to preventive measures (T2, two weeks after T1), loneliness, negative and positive affect, frequency of social interactions, and perceived social support (T3, two weeks after T2). Results: Prevention scores (T1) increased the adherence to health behaviors (T2), which then predicted negative affect (T3). Exploratory results further showed that prevention scores predicted more loneliness and more negative affect (T3), but only for individuals with fewer social interactions and less perceived social support. Conclusions: Security motives in threatening times can be a double edge sword, with benefits for health behaviors and negative consequences for personal well-being. Having a strong social network during these times appears to alleviate these consequences.
  🖺 Full Text HTML: Security motives and personal well-being during the early months of the COVID-19 pandemic
• The Impact of Intolerance of Uncertainty on Reappraisal and Suppression -
  The uncertainty of the COVID-19 pandemic highlights the importance of understanding how attitudes towards uncertainty affect well-being. Intolerance of uncertainty is a trait associated with anxiety, worry, and mood disorders. As adaptive emotion regulation supports well-being and mental health, it is possible that intolerance of uncertainty decreases the capacity to use adaptive emotion regulation and increases the use of maladaptive strategies. However, little research exists on the relationship between intolerance of uncertainty and use of cognitive emotion regulation strategies, such as reappraisal and suppression. Study 1 demonstrated that scores on the Intolerance of Uncertainty Scale were associated with greater worry related to the COVID-19 pandemic, decreased capacity to implement reappraisal, and greater self-reported use of suppression in daily life. Study 2 provided a preregistered replication of these findings. These results suggest that intolerance of uncertainty may impact mental health by reducing the capacity and tendency to use adaptive emotion regulation.
  🖺 Full Text HTML: The Impact of Intolerance of Uncertainty on Reappraisal and Suppression
• Anxiety, Knowledge, Misconceptions, and Health-Seeking Behavioral Intentions in Brazil COVID-19 Pandemic: A network psychometric approach -
  SARS-CoV-2 pandemic has spread rapidly worldwide, causing life-changing and affecting anxiety, misconceptions, knowledge, and people’s health behavioral intentions, which need adhering to COVID-19 prevention practices. Thus, it is relevant to develop psychometric measures for those variables on different populations. The goal of the present research is to seek evidence of validity and reliability of the Fear and Health-Seeking Behavioral Intentions Scales in a Brazilian sample. To do so, this research used recent developments in the field of network psychometrics. Using a sample of 476 Brazilians collected at the beginning of the pandemic, we found a four-dimensional structure in the reflective variables, forming a sound structure with good psychometric properties. In addition, using the novel approach to see the relationship between those variables, novel findings are discussed. We highlighted the importance of COVID-19 anxiety in the network structure, as it can be a possible alternative to increase adherence to prevent COVID-19 infection.

• Mental health of adults in Ireland during the first year of the COVID-19 pandemic: Results from a nationally representative, longitudinal study -
  Objective: Emerging evidence indicates that the mental health consequences of COVID-19 may not be as deleterious as initially feared. We analyzed the levels of symptom expression and rates of Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and COVID-19 related Posttraumatic Stress Disorder (C19-PTSD) in the adult population of Ireland at different points during the first year of the pandemic. Methods: Data were collected from a nationally representative sample of 1041 adults across five waves from March/April 2020 to March/April 2021. New participants were recruited at follow-up waves to maintain nationally representative cross-sectional estimates. Cross- sectional estimates of each and any disorder were calculated, and longitudinal changes in means and prevalence estimates of MDD, GAD, and C19-PTSD were assessed using structural equation modelling. Results: Cross-sectional estimates of meeting criteria for MDD, GAD, or C19-PTSD were 34.7% in March/April 2020 (Wave 1) and 33.7% in March/April 2021 (Wave 5). Longitudinal analyses revealed no significant change in symptoms of MDD, a significant decrease in GAD symptoms, and a significant increase in C19-PTSD symptoms. There were significant decreases in prevalence estimates of MDD (by 4.9%) and GAD (by 6.3%), and no significant change in C19-PTSD. Overall, 4.7% fewer people met criteria for any disorder at Wave 5 than at Wave 1. Conclusion: There was no evidence of an increase in mental health problems in the adult population during the first year of the pandemic in Ireland. Analyses of longitudinal data indicated a small but significant decrease in the proportion of people suffering from a mental health disorder.
  🖺 Full Text HTML: Mental health of adults in Ireland during the first year of the COVID-19 pandemic: Results from a nationally representative, longitudinal study
• Video-based messages to reduce COVID-19 vaccine hesitancy and nudge uptake -
  Vaccines are highly effective for curbing the spread of SARS-CoV-2. Yet, millions of Americans remain hesitant about getting vaccinated, jeopardizing the collective benefits from potential herd immunity and our ability to end the COVID-19 pandemic. We show that brief video-based messages of encouragement addressing specific COVID-19 vaccine concerns increase vaccination intentions. Intentions, in turn, predict future vaccine uptake in our data. Our experiment also reveals that increased confidence in COVID-19 vaccines and perceived behavioral control to get vaccinated are the key psychological drivers influencing willingness to get vaccinated. Importantly, our messages only increased vaccination intentions among people who identify as conservative or moderates, while liberals are unaffected due to high levels of pre-existing vaccine acceptability. Our findings corroborate the real-world behavioral significance of vaccination intentions, and devise how even short, scalable online messages can provide governments and health authorities an inexpensive, yet effective tool for increasing COVID-19 vaccinations among populations most reluctant to get them.
  🖺 Full Text HTML: Video-based messages to reduce COVID-19 vaccine hesitancy and nudge uptake
• The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2 -
  VIR-7831 and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VIR-7831 and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an LS mutation in the Fc region to prolong serum half-life and potentially enhance distribution to the respiratory mucosa. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. VIR-7831 and VIR-7832 potently neutralize wild-type and variant authentic virus in vitro as well as variant pseudotyped viruses. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to currently authorized mAbs. The VIR-7831/VIR-7832 epitope does not overlap with mutational sites in current variants of concern and continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with VIR-7831 had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that VIR-7831 and VIR-7832 are promising new agents in the fight against COVID-19.

From Clinical Trials

• Prophylaxis of COVID-19 Disease With Ivermectin in COVID-19 Contact Persons [German: Prophylaxe Der COVID-19-Erkrankung Mit Ivermectin Bei COVID-19 Kontaktpersonen] - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Placebo
  Sponsors:  
  Infectopharm Arzneimittel GmbH;   GKM Gesellschaft für Therapieforschung mbH
  Not yet recruiting

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of COVID-19 Vaccine, CT-COV-21 Extension Study - Condition:   Covid19 Vaccine
  Intervention:   Biological: MVC-COV1901(S protein with adjuvant)
  Sponsor:   Medigen Vaccine Biologics Corp.
  Enrolling by invitation

• Safety and Immunogenicity Study of AdCLD-CoV19-1: A COVID-19 Preventive Vaccine in Healthy Volunteers - Condition:   Covid19
  Intervention:   Biological: AdCLD-CoV19-1
  Sponsor:  
  Cellid Co., Ltd.
  Recruiting

• A Post-Exposure Prophylaxis Study of PF-07321332/Ritonavir in Adult Household Contacts of an Individual With Symptomatic COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Placebo for PF-07321332;   Drug: Placebo for Ritonavir;   Drug: Ritonavir
  Sponsor:   Pfizer
  Recruiting

• A Study of AZD1222, a Vaccine for the Prevention of COVID-19 in Immunocompromised Adults - Condition:   COVID-19, SARS-CoV-2
  Intervention:   Biological: AZD1222
  Sponsor:  
  AstraZeneca
  Not yet recruiting

• “Efesovir” (FS-1) for COVID-19, Phase 2 - Condition:   Covid19
  Intervention:   Drug: Efesovir
  Sponsor:   Scientific Center for Anti-infectious Drugs, Kazakhstan
  Not yet recruiting

• SARS-CoV-2 Infection in COVID-19 Vaccinated Patients - Condition:   COVID-19
  Intervention:   Diagnostic Test: COVID-19 vaccinated people
  Sponsor:   Hospices Civils de Lyon
  Recruiting

• The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores - Condition:   COVID-19 Pneumonia
  Intervention:   Biological: Bacillus subtilis
  Sponsor:   DreamTec Research Limited
  Recruiting

• Factors Influencing the COVID-19 Vaccine Immune Response According to Age and Presence or Not of a Past History of COVID-19 - Condition:   Covid19
  Interventions:   Biological: COVID-19 vaccine Pfizer (2 doses);   Biological: COVID-19 vaccine Pfizer (1 dose);   Biological: COVID-19 mRNA Vaccine Moderna (2 doses);   Biological: COVID-19 mRNA Vaccine Moderna (1 dose)
  Sponsors:   Centre Hospitalier Universitaire de Saint Etienne;   Sanofi Pasteur, a Sanofi Company;   Bioaster
  Not yet recruiting

• Relate to the Virus That Causes COVID-19, Known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Condition:   Covid19
  Intervention:   Other: Rapid antigen testing kit
  Sponsors:  
  Mahidol University;   Yuvabadhana foundation;   Zero COVID Thailand
  Not yet recruiting

• Test to Stay in School: COVID-19 Testing Following Exposure in School Communities - Condition:   Covid19
  Intervention:   Other: COVID-19 Testing
  Sponsor:  
  Duke University
  Not yet recruiting

• FLuticasone in cOvid Treatment (FLOT) - Condition:   Covid19
  Intervention:   Drug: Fluticasone Propionate
  Sponsor:  
  University of Medicine and Pharmacy at Ho Chi Minh City
  Recruiting

• Efficacy and Safety of Baricitinib in Patients With Moderate and Severe COVID-19 - Condition:   Covid19
  Interventions:   Drug: Baricitinib;   Drug: Placebo
  Sponsor:  
  Incepta Pharmaceuticals Ltd
  Not yet recruiting

• Randomized Trial of COVID-19 Booster Vaccinations (Cobovax Study) - Condition:   COVID-19 Vaccination
  Interventions:   Biological: BNT162b2;   Biological: CoronaVac
  Sponsor:   The University of Hong Kong
  Not yet recruiting

• RCT on the Efficacy of Dexamethasone Versus Methyl Prednisolone in Covid-19 Infected Patients With High Oxygen Flow - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Dexamethasone;   Drug: Methylprednisolone
  Sponsor:   Cairo University
  Recruiting

From PubMed

• COVID-19 and Adult-onset Still’s Disease as part of Hyperferritinemic Syndromes - The coronavirus disease (COVID-19) is known to cause hyperferritinemia and hemophagocytic lymphohistiocytosis (HLH). Including this laboratory parameter, clinical symptoms similar to COVID-19 have been observed in adult-onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (CAPS), macrophage activation syndrome (MAS), and septic shock, which has led to the proposal of a concept called ‘hyperferritinemic syndromes.’ Additionally, high levels of some clinical markers in both…

• Mucus targeting as a plausible approach to improve lung function in COVID-19 patients - COVID-19 (SARS-CoV-2) has emerged as one of the worst pandemics that have tormented the globe due to its highly contagious nature. Even if the disease manifests fever-like symptoms mostly, the disease may progress to the pulmonary- hyper inflammatory phase, with severe pneumonia, hypoxia and subsequent multiple organ infection. This subsequently creates a huge burden to the health care systems across the globe for an immediate arrangement of ventilator facilities, oxygen supply and advanced…

• Repurposing fusion inhibitor peptide against SARS-CoV-2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for this viral pathogen due to their efficacy, safety, and specificity. In this study, seventeen antiviral peptides which were known to inhibit SARS-CoV-1 are collected and computationally screened against…

• Repurposing the antibacterial drugs for inhibition of SARS-CoV2-PLpro using molecular docking, MD simulation and binding energy calculation - Papain-like protease (nsp-3; non-structural protein) of novel corona virus is an ideal target for developing drugs as it plays multiple important functions for viral growth and replication. For instance, role of nsp-3 has been recognized in cleavage of viral polyprotein; furthermore, in infected host it weakens the immune system via downregulating the production of type I interferon. This downregulation is promoted by removal of ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from…

• Identification of potent inhibitors against transmembrane serine protease 2 for developing therapeutics against SARS-CoV-2 - In viral binding and entry, the Spike(S) protein of SARS-CoV-2 uses transmembrane serine protease 2 (TMPRSS2) for priming to cleavage themselves. In this study, we have screened ‘drug-like’ 7476 ligands and found that over thirty ligands can effectively inhibit the TMPRSS-2 better than the control ligand. Finally, the three best drug agents L1, L2, and L6 were selected according to their average binding affinities and fitting score. These ligands interact with Asp435, Cys437, Ser436, Trp461, and…

• Chronic circadian phase advance in male mice induces depressive-like responses and suppresses neuroimmune activation - Altered working and sleeping schedules during the COVID-19 pandemic likely impact our circadian systems. At the molecular level, clock genes form feedback inhibition loops that control 24-hr oscillations throughout the body. Importantly, core clock genes also regulate microglia, the brain resident immune cell, suggesting circadian regulation of neuroimmune function. To assess whether circadian disruption induces neuroimmune and associated behavioral changes, we mimicked chronic jetlag with a…

• Inhibitors of anti-apoptotic Bcl-2 family proteins exhibit potent and broad-spectrum anti-mammarenavirus activity via cell cycle arrest at G0/G1 phase - Targeting host factors is a promising strategy to develop broad-spectrum antiviral drugs. Drugs targeting anti-apoptotic Bcl-2 family proteins that were originally developed as tumor suppressors have been reported to inhibit multiplication of different types of viruses. However, the mechanisms whereby Bcl-2 inhibitors exert their antiviral activity remain poorly understood. In this study, we have investigated the mechanisms by which obatoclax (OLX) and ABT-737 Bcl-2 inhibitors exhibited a potent…

• Porcine deltacoronavirus enters porcine IPI-2I intestinal epithelial cells via macropinocytosis and clathrin- mediated endocytosis dependent on pH and dynamin - Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes serious diarrhoea in suckling piglets and has the potential for cross-species transmission. Although extensive studies have been reported on the biology and pathogenesis of PDCoV, the mechanisms by which PDCoV enters cells are not well characterized. In this study, we investigated how PDCoV enters IPI-2I cells, a line of porcine intestinal epithelial cells derived from pig ileum. Immunofluorescence assays, siRNA…

• Inhibitory Effects and Surface Plasmon Resonance-Based Binding Affinities of Dietary Hydrolyzable Tannins and Their Gut Microbial Metabolites on SARS-CoV-2 Main Protease - Severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (Mpro) inhibitors are considered as potential treatments for coronavirus disease 2019, and dietary polyphenols show promise in SARS-CoV-2 Mpro inhibition based on in silico studies. In the present study, we utilize a combination of biochemical-, surface plasmon resonance-, and docking- based assays to evaluate the inhibition and binding affinities of a series of tannins and their gut microbial metabolites on SARS-CoV-2 Mpro….

• Roadmap for the Management of Acute Undifferentiated Febrile Illness: An Expert Discussion and Review of Available Guidelines - Acute undifferentiated febrile illnesses (AUFIs) are associated with specific characterizations like fever of less than two weeks’ duration with no organ-specific symptoms at onset. These range from mild and self-limiting disease to progressive, life-threatening illness. Acute undifferentiated febrile illnesses are classified into malaria and non- malarial illnesses on the basis of microscopy or malariadiagnostic tests. Various challenges, such as comorbidities, geriatrics, pregnancy, and…

• Instant determination of the artemisinin from various Artemisia annua L. extracts by LC-ESI-MS/MS and their in- silico modelling and in vitro antiviral activity studies against SARS-CoV-2 - CONCLUSION: Further studies of these extracts for COVID-19 treatment will shed light to seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.

• Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium - Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic- COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature’-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC…

• Inhibition Mechanism of SARS-CoV-2 Main Protease with Ketone-Based Inhibitors Unveiled by Multiscale Simulations. Insights for Improved Designs - We present the results of classical and QM/MM simulations for the inhibition of SARS-CoV-2 3CL protease by a hydroxymethylketone inhibitor, PF-00835231. In the noncovalent complex the carbonyl oxygen atom of the warhead is placed in the oxyanion hole formed by residues 143 to 145, while P1-P3 groups are accommodated in the active site with similar interactions to those observed for the peptide substrate. According to alchemical free energy calculations, the P1’ hydroxymethyl group also…

• Extraction and characterization of metabolites from Olea europaea pulp and their molecular docking against SARS- CoV-2 main-protease (M(pro)) - The present study is the first to extract the bioactive metabolites from Olea europaea fruit using the Soxhlet- maceration extraction method. The preliminary phytochemical; Fourier transform-infrared spectroscopy (FT-IR); gas chromatography-mass spectrometry (GC-MS) analyses, and their potential against SARS-CoV-2 M^(pro) through molecular docking were studied. The preliminary qualitative phytochemical analyses showed coumarin glycosides, tannins, terpenoids, cholesterol, carbohydrates, and…

• Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication - Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is a virus-induced inflammatory disease of the airways and lungs that leads to severe multi-organ damage and death. Here we show that cellular lipid synthesis is required for SARS-CoV-2 replication and offers an opportunity for pharmacological intervention. Screening a short- hairpin RNA sublibrary that targets metabolic genes, we identified genes that either inhibit or promote SARS-CoV-2 viral infection, including…

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

• 治疗或预防新冠病毒的靶点 - 本发明提供一种蛋白片段，是如下至少一种：A1)氨基酸酸序列如SEQ ID NO.1所示；A2）氨基酸序列如SEQ ID NO.1第12位‑34位所示；A3）将A1)的蛋白片段的第18、19、28和29位中的任意一个或几个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A1)所示的蛋白片段具有90％以上的同一性的蛋白片段；A4）氨基酸酸序列如SEQ ID NO.2所示；A5）氨基酸序列如SEQ ID NO.2第32‑41位所示；A6）将A4)的蛋白片段的第35和36位中的任意1个或2个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A4)所示的蛋白片段具有90％以上的同一性的蛋白片段。 - 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

• 一种S1F-AXL复合物、试剂盒和检测该复合物的方法及应用 - 本发明公开了一种S1F‑AXL复合物、试剂盒和检测该复合物的方法及应用。所述试剂盒包含S1F多肽和AXL多肽，以S1F多肽、AXL多肽中的一种作为包被底物；所述S1F多肽和所述AXL多肽中至少一种为具有缀合标签的糖基化多肽，还包括具有微孔的微量滴定板、标记底物标记的抗标签特异性抗体、HRP偶联的二抗、洗涤缓冲液、标记底物反应液、反应终止液。所述检测S1F‑AXL复合物的试剂盒，通过测量标记的信号特征，检测S1F‑AXL复合物的结合亲和力，还可以用于检测来自怀疑感染了SARS‑CoV‑2(Covid‑19)的受试者的生物样品中的病毒。 - link

• 一种检测新型冠状病毒的引物探针组合及其应用 - 本发明提供了一种检测新型冠状病毒的引物探针组合及其应用，所述检测新型冠状病毒的引物探针组合包括特异性扩增并检测2019‑nCoV的ORF1ab基因、核壳蛋白N基因和刺突蛋白S基因N501Y突变位点的特异性引物对和探针。本发明还提供了一种检测新型冠状病毒的试剂盒及其以非疾病诊断和/或治疗为目的的使用方法。本发明所述检测新型冠状病毒的引物探针组合具有良好的特异性与灵敏度，配合优化后的检测体系，可以对待测样本进行快速准确的检测，并可以对整个实验流程进行监控，降低假阳性以及假阴性检测结果的出现概率，具有重要的意义。 - 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