Covid-19 Sentry

Contents

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

From Preprints

• Background rates of all-cause mortality, hospitalizations, and emergency department visits among nursing home residents in Ontario, Canada to inform COVID-19 vaccine safety assessments -

  Background. Nursing home (NH) residents are prioritized for COVID-19 vaccination. We report monthly mortality, hospitalizations, and emergency department (ED) visit incidence rates (IRs) during 2010-2020 to provide context for COVID-19 vaccine safety assessments. Methods. We observed outcomes among NH residents using administrative databases. IRs were calculated by month, sex, and age group. Comparisons between months were assessed using one-sample t-tests; comparisons by age and sex were assessed using chi-squared tests. Results. From 2010-2019, there were 83,453 (SD: 652.4) NH residents per month, with an average of 2.3 (SD: 0.28) deaths, 3.1 (SD: 0.16) hospitalizations, and 3.6 (SD: 0.17) ED visits per 100 residents per month. From March to December 2020, mortality IRs were increased, but hospitalization and ED visit IRs were reduced (p<0.05). Conclusion. We identified consistent monthly mortality, hospitalization, and ED visit IRs during 2010-2019. Marked differences in these rates were observed during 2020, coinciding with the COVID-19 pandemic. Keywords: long-term care, mortality, hospitalization, baseline rates, COVID-19 vaccine safety

  🖺 Full Text HTML: Background rates of all-cause mortality, hospitalizations, and emergency department visits among nursing home residents in Ontario, Canada to inform COVID-19 vaccine safety assessments
• A Novel Smart City Based Framework on Perspectives for application of Machine Learning in combatting COVID-19 -

  The spread of COVID-19 across the world continues as efforts are being made from multi-dimension to curtail its spread and provide treatment. The COVID-19 triggered partial and full lockdown across the globe in an effort to prevent its spread. COVID-19 causes serious fatalities with United States of America recording over 3,000 deaths within 24 hours, the highest in the world for a single day and as of October 2020 has recorded a total of 270,642 death tolls. In this paper, we present a novel framework that intelligently combines machine learning models and internet of things (IoT) technology-specific in combatting COVID-19 in smart cities. The purpose of the study is to promote the interoperability of machine learning algorithms with IoT technology in interacting with a population and its environment with the aim of curtailing COVID-19. Furthermore, the study also investigates and discusses some solution frameworks, which can generate, capture, store and analyze data using machine learning algorithms. These algorithms are able to detect, prevent, and trace the spread of COVID-19, and provide better understanding of the virus in smart cities. Similarly, the study outlined case studies on the application of machine learning to help in the fight against COVID-19 in hospitals across the world. The framework proposed in the study is a comprehensive presentation on the major components needed for the integration of machine learning approaches with other AI-based solutions. Finally, the machine learning framework presented in this study has the potential to help national healthcare systems in curtailing the COVID-19 pandemic in smart cities. In addition, the proposed framework is poised as a point for generating research interests that will yield outcomes capable of been integrated to form an improved framework.

  🖺 Full Text HTML: A Novel Smart City Based Framework on Perspectives for application of Machine Learning in combatting COVID-19
• Monitoring SARS-CoV-2 variants alterations in Nice neighborhoods by wastewater nanopore sequencing -

  Background: Wastewater surveillance has been proposed as an epidemiological tool to define the prevalence and evolution of the SARS-CoV-2 epidemics. However, most implemented SARS-CoV-2 wastewater surveillance projects were relying on qPCR measurement of virus titers and did not address the mutational spectrum of SARS-CoV-2 circulating in the population. Methods: We have implemented a nanopore RNA sequencing monitoring system in the city of Nice (France, 550,000 inhabitants). Between October 2020 and March 2021, we monthly analyzed the SARS-CoV-2 variants in 113 wastewater samples collected in the main wastewater treatment plant and 20 neighborhoods. Findings: We initially detected the lineages predominant in Europe at the end of 2020 (B.1.160, B.1.177, B.1.367, B.1.474, and B.1.221). In January, a localized emergence of a variant (Spike:A522S) of the B.1.1.7 lineage occurred in one neighborhood. It rapidly spread and became dominant all over the city. Other variants of concern (B.1.351, P.1) were also detected in some neighborhoods, but at low frequency. Comparison with individual clinical samples collected during the same week showed that wastewater sequencing correctly identified the same lineages as those found in COVID-19 patients. Interpretation: Wastewater sequencing allowed to document the diversity of SARS-CoV-2 sequences within the different neighborhoods of the city of Nice. Our results illustrate how sequencing of sewage samples can be used to track pathogen sequence diversity in the current pandemics and in future infectious disease outbreaks.

  🖺 Full Text HTML: Monitoring SARS-CoV-2 variants alterations in Nice neighborhoods by wastewater nanopore sequencing
• Three-step rhythmic breathing exercise and COVID-19: A cross-sectional study -

  Introduction: The present study assessed the prevalence of COVID-19 among people practicing three-step rhythmic breathing (3SRB) exercise and those who were not practicing any breathing exercises, including 3SRB exercise. Methods: A community-based cross-sectional observational study was conducted. Data was collected using a self-constructed online google survey tool from July 2020 to August 2020. Results: Out of a total 1083 sample, a higher proportion of the participants (41.3%) belonged to the 34-49 years age group, followed by the age group of 50-65 (32.5%). The sample was almost equally distributed; about 51.9% of the population was male, and 48.4% were female. The COVID-19 positivity was recorded almost double (3.1%) in groups not practicing 3SRB exercises compared to a group (1.3%) practicing 3SRB exercises. Furthermore, the practice of 3SRB was significantly associated with a lower percentage of COVID-19 infection (p=0.046). Conclusions: Practice of 3SRB is significantly associated with a lower percentage of COVID-19 infection. A future study with a robust methodology is warranted to validate the findings of this study and determine the effects of 3SRB on physiological and biological markers.

  🖺 Full Text HTML: Three-step rhythmic breathing exercise and COVID-19: A cross-sectional study
• Myeloid-derived suppressor cells in the blood of Iranian COVID-19 patients -

  Abstract Background: A cytokine storm and lymphopenia are reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection associated with coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs) that both suppress T-cell function. Serum IL-6 and IL-8 levels seem to correlate with the number of blood MDSCs. Objective: To determine the frequency of MDSCs in severe COVID-19 patients from Iran and their correlations with serum IL-8 levels. Methods: 37 severe (8 on ventilation, 29 without ventilation) and 13 moderate COVID-19 patients together with 8 healthy subjects were enrolled at the Masih Daneshvari Hospital, Tehran-Iran between 10th April 2020- 9th March 2021. Clinical and biochemical features, serum and whole blood were obtained. CD14, CD15, CD11b and HLA-DR expression on MDSCs was measured by flow cytometry. Results: M-MDSCs (P≤0.0001) and G-MDSCs (P≤0.0001) frequency were higher in Iranian COVID-19 patients compared to healthy subjects. M-MDSC frequency was higher in non-ventilated compared to moderate COVID-19 subjects (P=0.004). Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (P=0.03). IL8 level was significant difference in ventilated, non-ventilated and moderate patients (P=0.005). The frequency of G-MDSCs correlated negatively with INR (r=-0.39, P=0.02). Conclusion: Serum IL-8 levels did not correlate with the number of systemic MDSCs in COVID-19 patients. The highest levels of M-MDSCs were seen in the blood of severe non-ventilated patients. MDSC frequency in blood in the current study did not predict the survival and severity of COVID-19 patients. Keywords: MDSC, IL-8, COVID-19, peripheral blood

  🖺 Full Text HTML: Myeloid-derived suppressor cells in the blood of Iranian COVID-19 patients
• COVID-19 Serology Control Panel Using the Dried Tube Specimen Method -

  We used the dried tube specimen (DTS) procedure to develop the COVID-19 Serology Control Panel ( CSCP). The CSCP contains five well-characterized SARS-CoV-2 pooled plasma samples made available for labs around the world to compare test kits, use for external quality assurance, harmonize laboratory testing, and train laboratory workers.

• Decoding Clinical Biomarker Space of COVID-19: Exploring Matrix Factorization-based Feature Selection Methods -

  One of the most critical challenges in managing complex diseases like COVID-19 is to establish an intelligent triage system that can optimize the clinical decision-making at the time of a global pandemic. The clinical presentation and patients9 characteristics are usually utilized to identify those patients who need more critical care. However, the clinical evidence shows an unmet need to determine more accurate and optimal clinical biomarkers to triage patients under a condition like the COVID-19 crisis. Here we have presented a machine learning approach to find a group of clinical indicators from the blood tests of a set of COVID-19 patients that are predictive of poor prognosis and morbidity. Our approach consists of two interconnected schemes: Feature Selection and Prognosis Classification. The former is based on different Ma- trix Factorization (MF)-based methods, and the latter is performed using Random Forest algorithm. Our model reveals that Arterial Blood Gas (ABG) O2 Saturation and C-Reactive Protein (CRP) are the most important clinical biomarkers determining the poor prognosis in these patients. Our approach paves the path of building quantitative and optimized clinical management systems for COVID-19 and similar diseases.

  🖺 Full Text HTML: Decoding Clinical Biomarker Space of COVID-19: Exploring Matrix Factorization-based Feature Selection Methods
• Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2 -
  P.1. or gamma variant also known as the Brazil variant, is one of the variants of concern (VOC) which appears to have high transmissibility and mortality. To explore the potency of the CT-P59 monoclonal antibody against P.1 variant, we tried to conduct binding affinity, in vitro neutralization, and in vivo animal tests. In in vitro assays revealed that CT-P59 is able to neutralize P.1 variant in spite of reduction in its binding affinity against a RBD (receptor binding domain) mutant protein including K417T/E484K/N501Y and neutralizing activity against P.1 pseudoviruses and live viruses. In contrast, in vivo hACE2 (human angiotensin-converting enzyme 2)-expressing TG (transgenic) mouse challenge experiment demonstrated that a clinically relevant or lower dosages of CT-P59 is capable of lowering viral loads in the respiratory tract and alleviates symptoms such as body weight losses and survival rates. Therefore, a clinical dosage of CT-P59 could compensate for reduced in vitro antiviral activity in P.1-infected mice, implying that CT-P59 has therapeutic potency for COVID-19 patients infected with P.1 variant.
  🖺 Full Text HTML: Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2
• Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine -
  Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.
  🖺 Full Text HTML: Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine
• A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses -
  The SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane as demonstrated by cryo-electron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses, and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2 contaminated surfaces.
  🖺 Full Text HTML: A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses
• Impact of temperature on the affinity of SARS-CoV-2 Spike for ACE2 -
  The seasonal nature in the outbreaks of respiratory viral infections with increased transmission during low temperatures has been well established. The current COVID-19 pandemic makes no exception, and temperature has been suggested to play a role on the viability and transmissibility of SARS-CoV-2. The receptor binding domain (RBD) of the Spike glycoprotein binds to the angiotensin-converting enzyme 2 (ACE2) to initiate viral fusion. Studying the effect of temperature on the receptor-Spike interaction, we observed a significant and stepwise increase in RBD-ACE2 affinity at low temperatures, resulting in slower dissociation kinetics. This translated into enhanced interaction of the full Spike to ACE2 receptor and higher viral attachment at low temperatures. Interestingly, the RBD N501Y mutation, present in emerging variants of concern (VOCs) that are fueling the pandemic worldwide, bypassed this requirement. This data suggests that the acquisition of N501Y reflects an adaptation to warmer climates, a hypothesis that remains to be tested.
  🖺 Full Text HTML: Impact of temperature on the affinity of SARS-CoV-2 Spike for ACE2
• Host cell membrane capture by the SARS CoV-2 spike protein fusion intermediate -
  Cell entry by SARS-CoV-2 is accomplished by the S2 subunit of the spike S protein on the virion surface by capture of the host cell membrane and fusion with the viral envelope. Capture and fusion require the prefusion S2 to transit to its potent, fusogenic form, the fusion intermediate (FI). However, the FI structure is unknown, detailed computational models of the FI are unavailable, and the mechanisms and timing of membrane capture and fusion are not established. Here, we constructed a full-length model of the CoV-2 FI by extrapolating from known CoV-2 pre- and postfusion structures. In atomistic and coarse-grained molecular dynamics simulations the FI was remarkably flexible and executed large bending and extensional fluctuations due to three hinges in the C-terminal base. Simulations suggested a host cell membrane capture time of ~ 2 ms. Isolated fusion peptide simulations identified an N-terminal helix that directed and maintained binding to the membrane but grossly underestimated the binding time, showing that the fusion peptide environment is radically altered when attached to its host fusion protein. The large configurational fluctuations of the FI generated a substantial exploration volume that aided capture of the target membrane, and may set the waiting time for fluctuation-triggered refolding of the FI that draws the viral envelope and host cell membrane together for fusion. These results describe the FI as a machinery designed for efficient membrane capture and suggest novel potential drug targets.
  🖺 Full Text HTML: Host cell membrane capture by the SARS CoV-2 spike protein fusion intermediate
• Endothelial cell-activating antibodies in COVID-19 -

  Objectives: Patients with coronavirus disease 19 (COVID-19) are at high risk for fibrin-based occlusion of vascular beds of all sizes. Considering endothelial cell activation has regularly been described as part of the COVID-19 thrombo-inflammatory storm, we aimed to find upstream mediators of this activation. Methods: Cultured endothelial cells were exposed to sera or plasma from 244 patients hospitalized with COVID-19 or plasma from 100 patients in the intensive care unit with sepsis. Cell adhesion molecules E-selectin, VCAM-1, and ICAM-1 were detected by in-cell ELISA. Soluble E-selectin was measured in serum. Results: As compared with healthy controls, sera and plasma from patients with COVID-19, and to a lesser extent plasma from patients with sepsis, increased expression of E-selectin, VCAM-1, and ICAM-1 on cultured endothelial cells. We found modest correlations between serum neutrophil extracellular trap (NET) remnants and upregulation of cell adhesion molecules on endothelial cells. A stronger marker of the ability of COVID-19 serum to activate endothelial cells was the presence of circulating antiphospholipid antibodies, specifically anticardiolipin IgG and IgM and anti-phosphatidlyserine/prothrombin (anti-PS/PT) IgG and IgM. Depletion of total IgG from anticardiolipin-positive and anti-PS/PT-positive samples markedly restrained upregulation of E-selectin, VCAM-1, and ICAM-1. At the same time, supplementation of control serum with patient IgG was sufficient to trigger endothelial cell activation. Conclusions: These data are the first to suggest that some patients with COVID-19 have potentially diverse antibodies that drive endothelial cell activation in COVID-19. The data also add important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.

  🖺 Full Text HTML: Endothelial cell-activating antibodies in COVID-19
• Rationally designed immunogens enable immune focusing to the SARS-CoV-2 receptor binding motif -
  Eliciting antibodies to surface-exposed viral glycoproteins can lead to protective responses that ultimately control and prevent future infections. Targeting functionally conserved epitopes may help reduce the likelihood of viral escape and aid in preventing the spread of related viruses with pandemic potential. One such functionally conserved viral epitope is the site to which a receptor must bind to facilitate viral entry. Here, we leveraged rational immunogen design strategies to focus humoral responses to the receptor binding motif (RBM) on the SARS-CoV-2 spike. Using glycan engineering and epitope scaffolding, we find an improved targeting of the serum response to the RBM in context of SARS- CoV-2 spike imprinting. Furthermore, we observed a robust SARS-CoV-2-neutralizing serum response with increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses and represents an adaptable design approach for targeting conserved epitopes on other viral glycoproteins.
  🖺 Full Text HTML: Rationally designed immunogens enable immune focusing to the SARS-CoV-2 receptor binding motif
• Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses -
  Exposure to a pathogen elicits an adaptive immune response aimed to control and eradicate. Interrogating the abundance and specificity of the naive B cell repertoire contributes to understanding how to potentially elicit protective responses. Here, we isolated naive B cells from 8 seronegative human donors targeting the SARS-CoV-2 receptor-binding domain (RBD). Single B cell analysis showed diverse gene usage with no restricted complementarity determining region lengths. We show that recombinant antibodies engage SARS-CoV-2 RBD, circulating variants, and pre- emergent coronaviruses. Representative antibodies signal in a B cell activation assay and can be affinity matured through directed evolution. Structural analysis of a naive antibody in complex with spike shows a conserved mode of recognition shared with infection-induced antibodies. Lastly, both naive and affinity-matured antibodies can neutralize SARS-CoV-2. Understanding the naive repertoire may inform potential responses recognizing variants or emerging coronaviruses enabling the development of pan-coronavirus vaccines aimed at engaging germline responses.
  🖺 Full Text HTML: Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses

From Clinical Trials

• Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: NTR-441;   Drug: Placebo
  Sponsor:  
  Neutrolis
  Recruiting

• COVID-19 Vaccinations With a Sweepstakes - Condition:   Covid19
  Intervention:   Behavioral: Philly Vax Sweepstakes
  Sponsors:  
  University of Pennsylvania;   Philadelphia Department of Public Health
  Active, not recruiting

• Covid-19 Virtual Recovery Study - Condition:   Covid19
  Interventions:   Behavioral: Strength RMT;   Behavioral: Strength RMT and nasal breathing;   Behavioral: Endurance RMT;   Behavioral: Endurance RMT and nasal breathing;   Behavioral: Low dose RMT
  Sponsor:   Mayo Clinic
  Not yet recruiting

• A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents - Condition:   Covid19 Vaccine
  Interventions:   Biological: MVC-COV1901(S protein with adjuvant);   Biological: MVC-COV1901(Saline)
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine;   Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   CanSino Biologics Inc.
  Not yet recruiting

• Efficacy of Amantadine Treatment in COVID-19 Patients - Condition:   Patients With Moderate or Severe COVID-19
  Intervention:   Drug: Amantadine
  Sponsors:   Noblewell;   Medical Research Agency (ABM);   Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
  Recruiting

• Covid-19 Patients Management During Home Isolation - Condition:   Covid19
  Interventions:   Procedure: Oxygen therapy and physical therapy;   Device: Oxygen therapy
  Sponsor:   Cairo University
  Recruiting

• A Different Use of The Aerosol Box in COVID-19 Patients; Internal Jugular Vein Cannulation - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: Internal jugular vein cannulation
  Sponsor:   Bakirkoy Dr. Sadi Konuk Research and Training Hospital
  Completed

• Remdesivir- Ivermectin Combination Therapy in Severe Covid-19 - Condition:   Covid19
  Intervention:   Drug: Ivermectin
  Sponsor:   Assiut University
  Not yet recruiting

• Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition:   Covid19
  Intervention:   Drug: cholecalciferol 6 lakh IU
  Sponsor:  
  Postgraduate Institute of Medical Education and Research
  Not yet recruiting

• Immunogenicity and Safety of an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: 23-valent pneumococcal polysaccharide vaccine;   Biological: Inactivated Hepatitis A Vaccine
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• The Role of Chlorhexidine in Minimizing the Viral Load Among COVID-19 Patients - Condition:   COVID-19
  Intervention:   Drug: Chlorhexidine digluconate, povidone iodine
  Sponsor:   King Abdulaziz University
  Not yet recruiting

• Phase 1 Intranasal Parainfluenza Virus Type 5-SARS CoV-2 S Vaccine in Healthy Adults - Condition:   Covid19
  Interventions:   Biological: CVXGA1 low dose;   Biological: CVXGA1 high dose
  Sponsor:   CyanVac LLC
  Not yet recruiting

• “CHANGE COVID-19 Severity” - Condition:   COVID-19 Infection
  Intervention:   Drug: Magnesium Citrate plus probiotic
  Sponsor:   Vanderbilt University Medical Center
  Recruiting

• Efficacy, Immunogenicity, and Safety of the Inactivated COVID-19 Vaccine (TURKOVAC) Versus the CoronaVac Vaccine - Condition:   Covid19
  Interventions:   Biological: TURCOVAC;   Biological: CoronaVac
  Sponsor:   Health Institutes of Turkey
  Recruiting

From PubMed

• MPI8 is Potent Against SARS-CoV-2 by Inhibiting Dually and Selectively the SARS-CoV-2 Main Protease and the Host Cathepsin L - A number of inhibitors have been developed for the SARS-CoV-2 main protease (MPro) as potential COVID-19 medications but little is known about their selectivity. Using enzymatic assays, we characterized inhibition of TMPRSS2, furin, and cathepsins B/K/L by more than a dozen of previously developed MPro inhibitors including MPI1-9, GC376, 11a, 10-1, 10-2, and 10-3. MPI1-9, GC376 and 11a all contain an aldehyde for the formation of a reversible covalent hemiacetal adduct with the MPro active site…

• Peptidomimetic alpha-Acyloxymethylketone Warheads with Six-Membered Lactam P1 Glutamine Mimic: SARS-CoV-2 3CL Protease Inhibition, Coronavirus Antiviral Activity, and in Vitro Biological Stability - Recurring coronavirus outbreaks, such as the current COVID-19 pandemic, establish a necessity to develop direct-acting antivirals that can be readily administered and are active against a broad spectrum of coronaviruses. Described in this Article are novel α-acyloxymethylketone warhead peptidomimetic compounds with a six-membered lactam glutamine mimic in P1. Compounds with potent SARS-CoV-2 3CL protease and in vitro viral replication inhibition were identified with low cytotoxicity and good…

• Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients - CONCLUSIONS: The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

• Targeting autophagy in disease: established and new strategies - Macroautophagy/autophagy is an evolutionarily conserved pathway responsible for clearing cytosolic aggregated proteins, damaged organelles or invading microorganisms. Dysfunctional autophagy leads to pathological accumulation of the cargo, which has been linked to a range of human diseases, including neurodegenerative diseases, infectious and autoimmune diseases and various forms of cancer. Cumulative work in animal models, application of genetic tools and pharmacologically active compounds, has…

• In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses - Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs…

• Targeting liquid-liquid phase separation of SARS-CoV-2 nucleocapsid protein promotes innate antiviral immunity by elevating MAVS activity - Patients with Coronavirus disease 2019 exhibit low expression of interferon-stimulated genes, contributing to a limited antiviral response. Uncovering the underlying mechanism of innate immune suppression and rescuing the innate antiviral response remain urgent issues in the current pandemic. Here we identified that the dimerization domain of the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is required for SARS2-NP to undergo liquid-liquid phase separation with RNA, which inhibits Lys63-linked…

• A bivalent protein targeting glycans and HR1 domain in spike protein potently inhibited infection of SARS-CoV-2 and other human coronaviruses - CONCLUSIONS: Since GL25E showed highly potent and broad-spectrum inhibitory activity against infection of SARS-CoV-2 and its mutants, as well as other HCoVs, it is a promising candidate for further development as a broad-spectrum anti-HCoV therapeutic and prophylactic to treat and prevent COVID-19 and other emerging HCoV diseases.

• Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization - The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India^(1-5). It has since then become dominant in some indian regions and UK and further spread to many countries⁶. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), harbouring diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2, also termed variant Delta, is believed to spread faster than other…

• Multifunctional inhibitors of SARS-CoV-2 by MM/PBSA, essential dynamics, and molecular dynamic investigations - The ongoing COVID-19 pandemic demands a novel approach to combat and identify potential therapeutic targets. The SARS- CoV-2 infection causes a hyperimmune response followed by a spectrum of diseases. Limonoids are a class of triterpenoids known to prevent the release of IL-6, IL-15, IL-1α, IL-1β via TNF and are also known to modulate PI3K/Akt/GSK-3β, JNK1/2, MAPKp38, ERK1/2, and PI3K/Akt/mTOR signaling pathways and could help to avoid viral infection, persistence, and pathogenesis. The present…

• AIEgen-loaded nanofibrous membrane as photodynamic/photothermal antimicrobial surface for sunlight-triggered bioprotection - The outbreak of infectious diseases such as COVID-19 causes an urgent need for abundant personal protective equipment (PPE) which leads to a huge shortage of raw materials. Additionally, the inappropriate disposal and sterilization of PPE may result in a high risk of cross-contamination. Therefore, the exploration of antimicrobial materials possessing both microbe interception and self-decontamination effects to develop reusable and easy-to-sterilize PPE is of great importance. Herein, an…

• PROTECTIVE ROLE OF CORTISTATIN IN PULMONARY INFLAMMATION AND FIBROSIS - CONCLUSION AND IMPLICATIONS: We identify to cortistatin as an endogenous break of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor-prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin- based therapies emerge as attractive candidates to treat severe ALI/ARDS, including SARS-Cov-2-associated ARDS.

• Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics - Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries. The active compounds isolated from T. riparia are known to possess various biological…

• Efficacy of tocilizumab in COVID-19: A review of the current evidence - As cases of coronavirus 2019 (COVID-19) keep rising, reported deaths are increasing. Public health measures have been implemented with mixed efficacy. As vaccines are becoming more widely available and accessible globally, treating critically ill COVID-19 patients remains an issue with only dexamethasone found to be therapeutically effective to date. However, trials studying the efficacy of IL-6 inhibitors, namely tocilizumab have been underway with promising results. This paper is a narrative…

• Therapeutic potential of phytoconstituents of edible fruits in combating emerging viral infections - Plant-derived bioactive molecules display potential antiviral activity against various viral targets including mode of viral entry and its replication in host cells. Considering the challenges and search for antiviral agents, this review provides substantiated data on chemical constituents of edible fruits with promising antiviral activity. The bioactive constituents like naringenin, mangiferin, α-mangostin, geraniin, punicalagin, and lectins of edible fruits exhibit antiviral effect by…

• Inhibition of the 3CL Protease and SARS-CoV-2 Replication by Dalcetrapib - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3CL protease is a promising target for inhibition of viral replication by interaction with a cysteine residue (Cys145) at its catalytic site. Dalcetrapib exerts its lipid- modulating effect by binding covalently to cysteine 13 of a cholesteryl ester transfer protein. Because 12 free cysteine residues are present in the 3CL protease, we investigated the potential of dalcetrapib to inhibit 3CL protease activity and SARS-CoV-2…

From Patent Search

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• SARS-CoV-2 anti-viral therapeutic - - link

• A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link

• 新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域，具体而言，提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒，具体包括（a）或（b）两种方案：（a）示踪物标记的RBD三聚体抗原，包被在固体支持物上的ACE2，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；（b）示踪物标记的ACE2，包被在固体支持物上的RBD三聚体抗原，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；其中，RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度，提升阳性样本平均发光强度，缩短检测时间。 - link

• 一种检测SARS-CoV-2的引物组合物及其应用 - 本发明涉及一种检测SARS‑CoV‑2的引物组合物及其应用。所述引物组合物包括SEQ ID NO:1~SEQ ID NO:12所示的核酸序列。本发明利用所述引物组合物进行逆转录巢式PCR，并结合Sanger测序，能够快速、准确地获取SARS‑CoV‑2基因信息，从而能够实现快速检测SARS‑CoV‑2以及判断SARS‑CoV‑2突变株，且具备良好的准确性、灵敏度、特异性以及重复性。 - link

• 一种新冠病毒肺炎重症化预测系统及方法 - 本发明涉及疾病预测技术领域，公开了一种新冠病毒肺炎重症化预测系统及方法，包括以下步骤：步骤一，采集患者血常规信息和用户信息；步骤二，将患者血常规信息按照用户信息进行等级分类；步骤三，将已经等级分类的患者血常规信息与对应等级的标准信息进行比较；步骤四，当患者血常规信息在标准信息范围内则判定患者为轻症患者，当患者血常规信息在标准信息范围外则判定患者为重症患者。本发明能够准确快速地区分轻症和重症。 - link

• MEDIDOR DE SATURACION - - link

• 폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link

• 백신 냉각 및 해동 기능을 갖는 백신 보관장치 - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - link