Covid-19 Sentry

Contents

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

From Preprints

• Inflammasome Treatment against Adverse Events of Special Interest -
  Background Adverse events of special interest (AESI) are associated with an elevated risk of myocarditis, lymphadenopathy, and death. Main body of the abstract We found a supplement that might reduce the risk of AESI induced by SARS-CoV-2 spike protein. The number of cases of AESI was reported to have the same patterns in the UK, South Korea, and Trials of mRNA vaccines among nine countries. The spike protein of SARS-CoV-2 damages hematopoietic stem/progenitor cells in an NLRP3 inflammasome-dependent manner. AESI might come from inflammasomes induced by mRNA vaccines expressing the full-length prefusion spike glycoprotein of SARS-CoV-2. Inflammasomes induced by the mRNA vaccine can induce AESI or biopsy‑proven lymphocytic myocarditis. Dapsone has been used to treat stroke, infective endocarditis, immune thrombocytopenia, Alzheimer’s disease, seizure, and COVID-19 ARDS. As an inflammasome competitor, dapsone can reduce inflammasome reactions. Conclusion Inflammasomes induced by mRNA vaccines can induce AESI or other inflammasome diseases, such as COVID-19. As an inflammasome competitor, dapsone can reduce inflammasome reactions.
  🖺 Full Text HTML: Inflammasome Treatment against Adverse Events of Special Interest
• SARS-CoV-2 evolution and patient immunological history shape the breadth and potency of antibody-mediated immunity -
  Since the emergence of SARS-CoV-2, humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody- mediated neutralisation responses against SARS-CoV-2 Wuhan, SARS-CoV-2a, SARS-CoV-2d and SARS-CoV-2o pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2 Wuhan, SARS-CoV-2a or SARS-CoV-2d, and vaccinated/infected individuals. We show that the breadth and potency of the antibody- mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.
  🖺 Full Text HTML: SARS-CoV-2 evolution and patient immunological history shape the breadth and potency of antibody-mediated immunity
• Modelling the within-host spread of SARS-CoV-2 infection, and the subsequent immune response, using a hybrid, multiscale, individual-based model. Part I: Macrophages. -
  Individual responses to SARS-CoV-2 infection vary significantly, ranging from mild courses of infection that do not require hospitalisation to the development of disease which not only requires hospitalisation but can be fatal. Whilst many immunological studies have revealed fundamental insights into SARS-CoV-2 infection and COVID-19, mathematical and computational modelling can offer an additional perspective and enhance understanding. The majority of mathematical models for the within-host spread of SARS-CoV-2 infection are ordinary differential equations, which neglect spatial variation. In this article, we present a hybrid, multiscale, individual-based model to study the within-host spread of SARS-CoV-2 infection. The model incorporates epithelial cells (each containing a dynamical model for viral entry and replication), macrophages and a subset of cytokines. We investigate the role of increasing initial viral deposition, increasing delay in type I interferon secretion from epithelial cells (as well as the magnitude of secretion), increasing macrophage virus internalisation rate and macrophage activation, on the spread of infection.
  🖺 Full Text HTML: Modelling the within-host spread of SARS-CoV-2 infection, and the subsequent immune response, using a hybrid, multiscale, individual-based model. Part I: Macrophages.
• GDF15 and ACE2 stratify COVID19 patients according to severity while ACE2 mutations increase infection susceptibility. -
  Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and healthy control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility.
  🖺 Full Text HTML: GDF15 and ACE2 stratify COVID19 patients according to severity while ACE2 mutations increase infection susceptibility.
• ORF6 protein of SARS-CoV-2 inhibits TRIM25 mediated RIG-I ubiquitination to mitigate type I IFN induction. -
  Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection confers a profound replication advantage on the virus and contributes to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host innate immune system and found that the ORF6 protein mitigated type-I IFN (interferon) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction and signaling. Here we show that ORF6 directly interacts with RIG-I and blocks downstream type-I IFN induction and signaling by inhibiting K-63 linked ubiquitination of RIG-I by the E3 Ligase TRIM25. This involves ORF6-mediated targeting of TRIM25 for degradation, also observed during SARS-CoV-2 infection. The type-I IFN antagonistic activity of ORF6 was mapped to its C-terminal cytoplasmic tail, specifically to amino acid residues 52-61. Overall, we provide new insights into how the SARS-CoV-2 ORF6 protein inhibits type I- IFN induction and signaling through distinct mechanisms.
  🖺 Full Text HTML: ORF6 protein of SARS-CoV-2 inhibits TRIM25 mediated RIG-I ubiquitination to mitigate type I IFN induction.
• Reaction Conditions Promoting the Specific Detection of SARS-CoV-2 NendoU Enzymatic Activity -
  Methods that enable rapid detection of SARS-CoV-2 provide valuable tools for detecting and controlling Covid-19 outbreaks and also facilitate more effective treatment of infected individuals. The predominant approaches developed use PCR to detect viral nucleic acids or immunoassays to detect viral proteins. Each approach has distinct advantages and disadvantages, but alternatives that do not share the same limitations could enable substantial improvements in outbreak detection and management. For instance, methods that have comparable sensitivity to PCR, but that are not prone to the false-positive results that stem from the tendency of PCR to detect molecular degradation products could improve accurate identification of infected individuals. An alternative approach with potential to achieve this entails harnessing the unique enzymatic properties of SARS-CoV-2 enzymes to generate SARS-Cov-2-specific signals that indicate the presence of the virus. This route benefits from the high sensitivity provided by enzymatic signal amplification and also the fact that signal is generated only by intact viral enzymes, not degradation products. Here, we demonstrate enzymatic reaction conditions that enable the preferential detection of NendoU of SARS-CoV-2, versus several of its orthologues, with a fluorogenic oligonucleotide substrate. These compositions provide a possible technical foundation for a novel approach for detecting SARS-CoV-2 that has distinct advantages from current approaches.
  🖺 Full Text HTML: Reaction Conditions Promoting the Specific Detection of SARS-CoV-2 NendoU Enzymatic Activity
• Immunological findings in a group of individuals who were non-responders to standard two-dose SARS-CoV-2 vaccines -
  Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic. The virus has infected more than 505 million people and caused more than 6 million deaths. However, data on non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of the study is to comprehensively compare the immunological characteristics of non-responders to SARS-CoV-2 vaccines in the 18-59 years with that in the 60 years and older using internationally recognized cutoff values. Participants included 627 individuals who received physical examinations and volunteered to participate in COVID-19 vaccination from the general population. The main outcome was an effective seroconversion characterized by anti-SARS-CoV-2 spike IgG level of at least 4-fold increase from baseline. Profiling of naive immune cells was analyzed prior to vaccination to demonstrate baseline immunity. Outcomes of effective seroconversion in the 18-59 years with that in the 60 years and older were compared. The quantitative level of the anti-spike IgG was significantly lower in the 60 years and older and in men among the 18-59 years. There were 7.5% of non-responders among the 18-59 years and 11.7% of non-responders in the 60 years and older using the 4-fold increase parameter. The effective seroconversion rate was significantly related to the level of certain immune cells before vaccination, such as CD4 cells, CD8 cells and B cells and the age. An individual with a titer of anti-SARS-CoV-2 spike IgG that is below 50 BAU/mL might be considered a non-responder between 14-90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended for non- responders as soon as possible to reduce disease severity and mortality.
  🖺 Full Text HTML: Immunological findings in a group of individuals who were non-responders to standard two-dose SARS-CoV-2 vaccines
• ACE2 nanoparticles prevent cell entry of SARS-CoV-2 -
  We have now been in the grip of the COVID-19 pandemic for over two years with devastating consequences. The continual evolution of the virus has challenged the efficacy of many vaccines and treatment options based on immunotherapies are compromised by this viral escape. One treatment strategy that averts viral escape is the use of constructs based on its entry receptor Angiotensin-Converting Enzyme 2 (ACE2) acting as decoys. Here, we combined full- length human ACE2 with viral vectors commonly used for gene therapy to form nanoparticles that present ACE2 on their surface analogous to human cells. Using cell-based assays and direct, multiscale imaging including cryogenic cellular tomography, we show that these ACE2 nanoparticles are highly efficient in preventing entry of SARS-CoV-2, the virus causing COVID-19, in model cell systems as well as human respiratory tract ex-vivo cultures. Thus, ACE2 nanoparticles have high potential as the next generation therapeutics for addressing the immediate needs of the current pandemic and possible future outbreaks.
  🖺 Full Text HTML: ACE2 nanoparticles prevent cell entry of SARS-CoV-2
• Repurposing BCG Vaccine to Protect my Parents, Children, and my Family against COVID-19: A Real-life Experience. -
  A first global family report, how a physician & scientist safely and effectively repurposed the very safe, very old, very economic live attenuated BCG vaccine to protect against COVID-19 complications for immunocompetent children, adults and geriatric participants.
  🖺 Full Text HTML: Repurposing BCG Vaccine to Protect my Parents, Children, and my Family against COVID-19: A Real-life Experience.
• Statistical Analysis Plan for the HydrOxychloroquine Prophylaxis Evaluation (HOPE) trial -
  HOPE is a prospective, multi-centre, parallel group, concealed, unblinded, randomized, controlled trial to determine whether combination of hydroxychloroquine and standard practice, that is, use of recommended personal protective equipment reduces the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers in hospitals in India as compared to standard practice. This detailed statistical analysis plan was prepared by trial statisticians and approved by the HOPE management committee prior to completion of data collection.
  🖺 Full Text HTML: Statistical Analysis Plan for the HydrOxychloroquine Prophylaxis Evaluation (HOPE) trial
• Explaining the existential: scientific and religious explanations play different functional roles -
  How did the universe come to exist? What happens after we die? Answers to existential questions tend to elicit both scientific and religious explanations, offering a unique opportunity to evaluate how these domains differ in their psychological roles. Across three studies (N = 1,215), one correlational, one experimental, and one capitalizing on a natural intervention (the onset of the COVID-19 pandemic), we find that scientific explanations tend to be attributed more epistemic virtues (such as evidential support and objectivity) and are more often generated to meet epistemic demands (Studies 1-2), whereas religious explanations tend to be attributed more non-epistemic virtues (such as offering emotional comfort and supporting moral behavior) and are more often generated to meet non-epistemic demands (Studies 1-3). Importantly, these effects are moderated by religiosity: religious believers attribute both epistemic and non- epistemic virtues to religious explanations, whereas those who are not religious attribute only epistemic virtues to scientific explanations. These findings inform theories of religious belief, the cognitive coexistence of supernatural and natural conceptions of life and death, and the relationship between epistemic and non-epistemic considerations.
  🖺 Full Text HTML: Explaining the existential: scientific and religious explanations play different functional roles
• SARS-CoV-2 Suppression and Early Closure of Bars and Restaurants : A Longitudinal Natural Experiment -

  Despite severe economic damage, full-service restaurants and bars have been closed in hopes of suppressing the spread of SARS-CoV-2 worldwide. This study explores whether the early closure of restaurants and bars in February 2021 reduced symptoms of SARS-CoV-2 in Japan. Using a large-scale nationally representative longitudinal survey, we found that the early closure of restaurants and bars decreased the utilization rate among young persons (OR 0.688; CI95 0.515?0.918) and those who visited these places before the pandemic (OR 0.754; CI95 0.594?0.957). However, symptoms such of SARS-CoV-2 did not decrease in these active and high-risk subpopulations. Among the more inactive and low-risk subpopulations, such as elderly persons, no discernible impacts are observed in both the utilization of restaurants and bars and the symptoms of SARS-CoV-2. These results suggest that the early closure of restaurants and bars without any other concurrent measures does not contribute to the suppression of SARS-CoV-2.

  🖺 Full Text HTML: SARS-CoV-2 Suppression and Early Closure of Bars and Restaurants : A Longitudinal Natural Experiment
• Validation of Reduced S-gene Target Performance and Failure for Rapid Surveillance of SARS-CoV-2 Variants -

  SARS-CoV-2, the virus that causes COVID-19, has many variants capable of rapid transmission causing serious illness. Timely surveillance of new variants is essential for an effective public health response. Ensuring availability and access to diagnostic and molecular testing is key to this type of surveillance. This study utilized reverse transcription polymerase chain reaction (RT-PCR) and whole genome sequencing results from COVID-19-positive patient samples obtained through a collaboration between Aegis Sciences Corporation and Walgreens Pharmacy that has conducted more than 8.5 million COVID-19 tests at ~5,200 locations across the United States and Puerto Rico. Viral evolution of SARS-CoV-2 can lead to mutations in the S-gene that cause reduced or failed S-gene amplification in diagnostic PCR tests. These anomalies, labeled reduced S-gene target performance (rSGTP) and S-gene target failure (SGTF), are characteristic of Alpha and Omicron (B.1.1.529, BA.1, and BA.1.1) lineages. This observation has been validated by whole genome sequencing and can provide presumptive lineage data following completion of diagnostic PCR testing in 24-48 hours from collection. Active surveillance of trends in PCR and sequencing results is key to the identification of changes in viral transmission and emerging variants. This study shows that rSGTP and SGTF can be utilized for near real- time tracking and surveillance of SARS-CoV-2 variants.

  🖺 Full Text HTML: Validation of Reduced S-gene Target Performance and Failure for Rapid Surveillance of SARS-CoV-2 Variants
• Predictors of all-cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS- CoV-2 -

  Background: Shared and divergent predictors of clinical severity across respiratory viruses may support clinical and community responses in the context of a novel respiratory pathogen. Methods: We conducted a retrospective cohort study to identify predictors of 30-day all-cause mortality following hospitalization with influenza (N=45,749; 2011-09 to 2019-05), respiratory syncytial virus (RSV; N=24,345; 2011-09 to 2019-04), or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; N=8,988; 2020-03 to 2020-12; pre-vaccine) using population- based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude, and confidence intervals of risk ratios to identify shared and divergent predictors of mortality. Results: 3,186 (7.0%), 697 (2.9%) and 1,880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS-CoV-2, respectively. Shared predictors of increased mortality included: older age, male sex, residence in a long-term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS-CoV-2. Few comorbidities were associated with mortality among patients with SARS-CoV-2 as compared to those with influenza or RSV. Conclusions: Our findings may help identify patients at greatest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local prevention and therapeutic strategies to communities with higher prevalence of risk factors.

  🖺 Full Text HTML: Predictors of all-cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS-CoV-2
• Time trends in social contacts of individuals according to comorbidity and vaccination status, before and during the COVID-19 pandemic: repeated cross-sectional population-based surveys -

  Background: As we are confronted with more transmissible/severe variants with immune escape and the waning of vaccine efficacy, it is particularly relevant to understand how the social contacts of individuals at greater risk of COVID-19 complications evolved over time. We described time trends in social contacts of individuals according to comorbidity and vaccination status before and during the first three waves of the COVID-19 pandemic in Quebec, Canada. Methods: We used data from CONNECT, a repeated cross-sectional population-based survey of social contacts conducted before (2018/2019) and during the pandemic (April 2020 to July 2021). We recruited non-institutionalized adults from Quebec, Canada, by random digit dialling. We used a self-administered web-based questionnaire to measure the number of social contacts of participants (two-way conversation at a distance ≤2 meters or a physical contact, irrespective of masking). We compared the mean number of contacts/day according to the comorbidity status of participants (pre-existing medical conditions with symptoms/medication in the past 12 months) and 1-dose vaccination status during the third wave. All analyses were performed using weighted generalized linear models with a Poisson distribution and robust variance. Results: A total of 1441 and 5185 participants with and without comorbidities, respectively, were included in the analyses. Contacts significantly decreased from a mean of 6.1 (95%CI 4.9-7.3) before the pandemic to 3.2 (95%CI 2.5-3.9) during the first wave among individuals with comorbidities, and from 8.1 (95%CI 7.3-9.0) to 2.7 (95%CI 2.2-3.2) among individuals without comorbidities. Individuals with comorbidities maintained fewer contacts than those without comorbidities in the second wave, with a significant difference before the Christmas 2020/2021 holidays (2.9 (95%CI 2.5-3.2) v 3.9 (95%CI 3.5-4.3); P<0.001). During the third wave, contacts were similar for individuals with (4.1, 95%CI 3.4-4.7) and without comorbidities (4.5, 95%CI 4.1-4.9; P=0.27). This could be partly explained by individuals with comorbidities vaccinated with their first dose who increased their contacts to the level of those without comorbidities. Conclusions: It will be important to closely monitor COVID-19-related outcomes and social contacts by comorbidity and vaccination status to inform targeted or population-based interventions (e.g., booster doses of the vaccine).

  🖺 Full Text HTML: Time trends in social contacts of individuals according to comorbidity and vaccination status, before and during the COVID-19 pandemic: repeated cross- sectional population-based surveys

From Clinical Trials

• Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial - Condition:   COVID-19
  Interventions:   Biological: Sinovac;   Biological: AZD1222;   Biological: BNT162b2
  Sponsors:   Albert B. Sabin Vaccine Institute;   Aga Khan University;   Oswaldo Cruz Foundation;   Stanford University
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E;   Biological: mRNA-1273
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19 - Condition:   COVID-19
  Intervention:   Drug: AmnioPul-02
  Sponsor:   Amniotics AB
  Not yet recruiting

• A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults. - Condition:   COVID-19
  Interventions:   Biological: 20 μg dose of SYS6006;   Biological: 30 μg dose of SYS6006;   Biological: 50 μg dose of SYS6006;   Drug: Placebo
  Sponsor:  
  CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
  Recruiting

• Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine - Condition:   Covid19
  Interventions:   Biological: A Lyophilized COVID-19 mRNA Vaccine;   Biological: Placebo
  Sponsor:   Jiangsu Rec-Biotechnology Co., Ltd.
  Not yet recruiting

• A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years. - Condition:   COVID-19
  Interventions:   Biological: 20 μg dose of SYS6006;   Biological: 30 μg dose of SYS6006;   Biological: 50 μg dose of SYS6006;   Drug: Placebo
  Sponsor:  
  CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
  Recruiting

• The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Chinese herbal medicine
  Sponsor:  
  Hong Kong Baptist University
  Not yet recruiting

• Home-based Exercise Program in Patients With the Post-COVID-19 Condition - Conditions:   Long COVID;   Post-acute COVID-19 Syndrome
  Intervention:   Other: Home- based physical training
  Sponsor:   University of Sao Paulo
  Not yet recruiting

• Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: NuSepin® 0.2 mg/kg;   Drug: NuSepin® 0.4 mg/kg;   Drug: Placebo
  Sponsor:   Shaperon
  Recruiting

• Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:   Drug: EXOFLO
  Sponsor:   Direct Biologics, LLC
  Not yet recruiting

• High Frequency Percussive Ventilation in COVID-19 Patients - Conditions:   COVID-19;   Acute Respiratory Failure
  Intervention:  
  Device: High frequency Percussive ventilation
  Sponsor:   University Magna Graecia
  Not yet recruiting

• VLA2001 Booster in Adult Participants After Natural SARS-CoV-2 Infection or Priming With an mRNA COVID-19 Vaccine - Condition:   SARS-CoV-2 Infection
  Intervention:   Biological: VLA2001
  Sponsor:  
  Valneva Austria GmbH
  Recruiting

• Knowledge Mobilization Activities to Support Decision-Making by Youth, Parents and Adults: Study Protocol - Condition:   COVID-19
  Interventions:   Other: Plain Language Recommendation (PLR);   Other: Standard Language Version (SLV)
  Sponsors:   McMaster University;   Western University;   The Hospital for Sick Children;   University of Alberta
  Not yet recruiting

• Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings - Conditions:   Covid19;   Diabetes Mellitus
  Intervention:   Device: continuous glucose monitoring
  Sponsor:   Tanureet K Arora
  Completed

• Study to Assess the Safety, Tolerability and Pharmacokinetics of STI-1558 in Healthy Volunteers - Condition:   COVID-19
  Interventions:   Drug: STI-1558;   Drug: Placebo
  Sponsor:  
  Sorrento Therapeutics, Inc.
  Not yet recruiting

From PubMed

• Biological activity of interferons in the novel coronavirus infection COVID-19 - CONCLUSION: The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.

• Bromhexine is a potential drug for COVID-19; From hypothesis to clinical trials - COVID-19 (novel coronavirus disease 2019), caused by the SARS-CoV-2 virus, has various clinical manifestations and several pathogenic pathways. Although several therapeutic options have been used to control COVID-19, none of these medications have been proven to be a definitive cure. Transmembrane serine protease 2 (TMPRSS2) is a protease that has a key role in the entry of SARS-CoV-2 into host cells. Following the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2…

• The problem of the use of interferons in the novel coronavirus disease COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) - By the end of 2021, about 200 studies on the effect of interferons (IFNs) on the incidence and course of the new coronavirus infection COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) have been reported worldwide, with the number of such studies steadily increasing. This review discusses the main issues of the use of IFN drugs in this disease. The literature search was carried out in the PubMed, Scopus, Cochrane Library, Web of Science, RSCI databases, as well as in the…

• Challenges for rapamycin repurposing as a potential therapeutic candidate for COVID-19: implications for skeletal muscle metabolic health in older persons - The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that has spread worldwide, resulting in over 6 million deaths as of March

2022. Older people have been disproportionately affected by the disease, as they have greater risk of hospitalization, are more vulnerable to severe infection, and have higher mortality than younger patients. Although effective vaccines have been rapidly developed…

• Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac - CONCLUSION: Low-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.

• Treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT) - Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel prothrombotic disorder characterized by thrombosis, thrombocytopenia, and disseminated intravascular coagulation identified in hundreds of recipients of ChAdOx1 nCoV-19 (Oxford/AstraZeneca), an adenovirus vector coronavirus disease 2019 (COVID-19) vaccine. VITT resembles heparin-induced thrombocytopenia (HIT) in that patients have platelet-activating anti-platelet factor 4 antibodies; however, whereas heparin typically enhances…

• Type I interferon regulates proteolysis by macrophages to prevent immunopathology following viral infection - The ability to treat severe viral infections is limited by our understanding of the mechanisms behind virus-induced immunopathology. While the role of type I interferons (IFNs) in early control of viral replication is clear, less is known about how IFNs can regulate the development of immunopathology and affect disease outcomes. Here, we report that absence of type I IFN receptor (IFNAR) is associated with extensive immunopathology following mucosal viral infection. This pathology occurred…

• Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies - CONCLUSION: IFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.

• 25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 M^pro and RdRp-: an insight from molecular docking and dynamics simulation approaches - The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (M^(pro)) of the virus mediate viral…

• Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an in silico perspective - During the past few months, mucormycosis has been associated with SARS-CoV-2 infections. Molecular docking combined with molecular dynamics simulation is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the…

• Potential Inhibitors of SARS-CoV-2 from Neocarya macrophylla (Sabine) Prance ex F. White: Chemoinformatic and Molecular Modeling Studies for Three Key Targets - CONCLUSION: The findings of this study have shown that N. macrophylla contains potential leads for SARS-CoV-2 inhibition and thus, should be studied further for development as therapeutic agents against COVID-19.

• IL-25 blockade augments antiviral immunity during respiratory virus infection - IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal…

• Megakaryocytes in pulmonary diseases - Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are…

• Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study - CONCLUSION: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.

• Artificial Neural Network-Based Study Predicts GS-441524 as a Potential Inhibitor of SARS-CoV-2 Activator Protein Furin: a Polypharmacology Approach - Furin, a pro-protein convertase, plays a significant role as a biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS-CoV-2, furin has become the center of attraction for researchers as the spike protein contains a polybasic furin cleavage site. In…

From Patent Search