- Evolutionary trajectory of the physicochemical mechanism of interaction of SARS-CoV-2 spike protein with ACE2 -
SARS-CoV-2 infects cells by attachment to its receptor the angiotensin converting enzyme 2 (ACE2). Regardless of the wealth of structural data, little is known about the physicochemical mechanism of interactions of the viral spike (S) protein with ACE2 and how this mechanism has evolved during the pandemic. Here, we applied experimental and computational approaches to characterize the molecular interaction of S proteins from SARS-CoV-2 variants of concern (VOC). Data on kinetics, activation- and equilibrium thermodynamics of binding of the receptor binding domain (RBD) from VOC with ACE2 as well as data from computational protein electrostatics revealed a profound remodeling of the physicochemical characteristics of the interaction during the evolution. Thus, as compared to RBDs from Wuhan strain and other VOC, Omicron RBD presented as a unique protein in terms of conformational dynamics and types of non-covalent forces driving the complex formation with ACE2. Viral evolution resulted in a restriction of the RBD structural dynamics, and a shift to a major role of electrostatic forces for ACE2 binding. Further, we investigated how the reshaping of the physicochemical qualities affect the functional properties of S proteins. Data from various binding assays revealed that SARS-CoV-2 Wuhan and Omicron RBDs manifest capacity for off-target (promiscuous) recognition of multiple unrelated proteins, but they harbor distinct reactivity patterns. This study provides mechanistic explanations for changes in the viral tropism, infectivity, and capacity to evade immune responses during evolution.
- The Effect of Perceived Workplace Bureaucracies on Self-Evaluated Efficacy, Job Satisfaction and Motivation in the Workplace during the COVID-19 Pandemic -
Workplace bureaucracies impact many areas of an employee’s life. Perceived high levels of bureaucracy can negatively impact employees’ job motivation, satisfaction, and performance. During the COVID-19 pandemic, infection containment measures may have contributed to the factors underlying the “great resignation” via the lack of self-efficacy from perceived bureaucracy. Recruiting 240 full-time employees in late 2021 to early 2022 across organisations in both private and public sectors in Singapore online with the Work Extrinsic Intrinsic Motivation Scale, the Workplace Bureaucracy Questionnaire and the General Self-Efficacy Scale among demographic parameters, 228 participants were analysed after removal of missing data. Salary range, education levels, employee self-efficacy and job motivation were found to be negatively associated with perceived workplace bureaucracies but not gender, age, and length of service. The findings of the study may provide insight into the mechanism of increased perceived bureaucracy during the COVID-19 pandemic on the employee experience that would be relevant to the workplace environment during in normal times.
- Un nuevo urbanismo para Europa: los fondos europeos de recuperación y su proyección en el futuro de las ciudades - A NEW URBANISM FOR EUROPE: THE EUROPEAN RECOVERY FUNDS, AND THEIR IMPACT ON THE FUTURE OF CITIES -
The Next Generation EU (NGEU) fund is a European Union economic recovery package to support member states adversely impacted by the COVID-19 pandemic. This program represents an unprecedented effort. Besides promoting a European Union more ecological, digital, and resilient, the recovery funds aim at financing projects of public-private partnership around a series of issues. Some especially related to urbanism, such as ecological transition, smart, sustainable, integrative growth, or social and territorial cohesion. In the first part of the present work, we analyze the evolution of urbanism in Europe since the 1972 European Soil Charter, adopted by the Council of Europe in Strasbourg. Secondly, we examine potential areas where urban projects could be promoted implementing European funds, in connection with the new Leipzig Charter and the European Territorial Agenda 2030, which support an urban environment more just, green, and productive.
- SARS-CoV-2 minor variant genomes at the start of the pandemic contained markers of VoCs -
SARS-CoV-2 emerged through limited zoonotic spillovers and was predicted to have constrained sequence diversity. The dominant consensus and minor variant genomes were determined from the earliest samples associated with the Huanan market and the start of the pandemic. The sequence data confirmed that the dominant consensus genomes shared very close homology. However, there were minor variant genomes present in each sample, which encompassed synonymous and non-synonymous changes. Fusion sequences characteristic of defective RNAs were identified that could be linked between patients. Several substitutions (but not deletions) associated with much later variants of concern (VoCs) were already present as minor variant genomes. This suggests it may be possible to predict futures variants at the start of a pandemic by examining where variability in sequence occurs.
- Inferring selection effects in SARS-CoV-2 with Bayesian Viral Allele Selection -
The global effort to sequence millions of SARS-CoV-2 genomes has provided an unprecedented view of viral evolution. Characterizing how selection acts on SARS-CoV-2 is critical to developing effective, long-lasting vaccines and other treatments, but the scale and complexity of genomic surveillance data make rigorous analysis challenging. To meet this challenge, we develop Bayesian Viral Allele Selection (BVAS), a principled and scalable probabilistic method for inferring the genetic determinants of differential viral fitness and the relative growth rates of viral lineages, including newly emergent lineages. After demonstrating the accuracy and efficacy of our method through simulation, we apply BVAS to 6.9 million SARS-CoV-2 genomes. We identify numerous mutations that increase fitness, including previously identified mutations in the SARS-CoV-2 Spike and Nucleocapsid proteins, as well as mutations in non-structural proteins whose contribution to fitness is less well characterized. In addition, we extend our baseline model to identify mutations whose fitness exhibits strong dependence on vaccination status as well as pairwise interaction effects, i.e. epistasis. Strikingly, both these analyses point to the pivotal role played by the N501 residue in the Spike protein. Our method, which couples Bayesian variable selection with a diffusion approximation in allele frequency space, lays a foundation for identifying fitness-associated mutations under the assumption that most alleles are neutral.
- Can starch-based diet or sugar water put an end to the COVID-19 pandemic? -
High valine plus glycine content is a feature of the proteins in SARS-CoV-2 and SARS viruses, and it causes the generation of aggregates between proteins and insoluble calcium salts via secondary chemical bonding. Starch-based diet or sugar water with adequate vitamins can go for many days without the generation of essential amino acids such as valine, creating bottlenecks in virion production in human body. Despite its potential carcinogenicity, modest lysine supplement can be favorable as lysine rich proteins gather chloride and solubilize stressful, insoluble and stiff calcium oxalate and calcium phosphate.
- The Prospective Relationship between Loneliness, Life Satisfaction, and Psychological Distress before and during the COVID-19 Pandemic in the UK -
Background Mental wellbeing in the UK seems to have deteriorated significantly during the COVID-19 pandemic, with the rates of loneliness, life satisfaction, and psychological distress taking longer to return to the pre-pandemic levels than elsewhere. Nevertheless, there is little knowledge about the interactions between these outcomes, or the factors that played a role. Methods Longitudinal data from Understanding Society (N=3475) were used to explore the changes in loneliness, life satisfaction, and psychological distress from pre-pandemic levels (2017-19) through November 2020, the interactions between these outcomes, and the role of individual differences in the rates of change, using multivariate latent growth curve model. Results Loneliness, life satisfaction, and psychological distress deteriorated minimally between April and November 2020, compared to the pre-pandemic levels (2017-2019), while the rate of change in each outcome influenced the rate of change in the other two. Key individual (age, gender, physical health), social (number of friends) and environmental (neighbourhood quality) variables influenced baseline scores and the rates of change. Conclusion Considering significant dynamic associations between loneliness, life satisfaction, and psychological distress, we argue that interventions to tackle any one of the outcomes may have beneficial effects on others, while highlighting individual and community-level interventions to tackle loneliness.
- Experiences of First Year University Students Regarding Institutional Mentoring Programme during COVID-19 Outbreak: A Qualitative Evidence Synthesis -
Universities had to ensure that students were well supported during the COVID-19 pandemic. Over the years, peer mentors have provided one-on-one psychosocial support to first-year students. Following the outbreak of COVID-19, it became difficult to provide face-to-face assistance. As a result, new forms of communities, networks, and interactions, that student can develop and participate in, emerged to cope with the crisis. The problem is that students encounter unexpected challenges from the moment they arrive at university, owing to the substantial shift in roles and complex responsibilities that comes with being a student at a university. The purpose of this study is to investigate students’ first-year experiences during the COVID-19 outbreak so as to provide insights that could be useful for institutional policy and practice. The study was undertake a Qualitative Evidence Systematic Review, which is a summary of research literature focused on a single subject that claims the role of systematic reviews in evidence-based practices. A qualitative meta-synthesis was conducted using the PICO framework (Population/Place; Intervention; Comparator; Outcome) so as to seek to answer the question: “What are the experiences of first-year university students regarding the institutional mentoring programme during the Covid-19 Outbreak?” Articles were critically reviewed for eligibility using the PRISMA flow diagram, with relevance screening and duplicate removal using the CASP assessment tool. This is a method that allows the researcher to evaluate data both deductively and interpretively to better understand phenomena. In total fifteen articles were selected for this study; they were chosen through purposive sampling and then subjected to thematic analysis. The findings of this study are expected to add to the existing body of knowledge on the first-year university student experience.
- The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis -
Objective This systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants. Methods The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). Results: The eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%). Conclusion There was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
- The impact of COVID-19 pandemic on influenza surveillance: a systematic review and meta-analysis -
Influenza activity was reported to be below the seasonal levels during the COVID-19 pandemic globally. However, during the SARS-CoV-2 outbreak, the routine real-time surveillance of influenza like illness (ILI) and acute respiratory infection (ARI) was adversely affected due to the changes in priorities, economic constraints, repurposing of hospitals for COVID care and closure of outpatient services. A systematic review and meta-analysis were carried out to assess the pooled proportion of symptomatic cases tested for influenza virus before the COVID-19 pandemic in 2019 and during the pandemic in 2020/2021. The study was designed based on PRISMA guidelines and the meta-analysis was performed to synthesise the pooled proportion of patients sampled for influenza surveillance before the COVID-19 pandemic in 2019 and during the pandemic in 2020/21 with 95% confidence interval (CI). The overall pooled proportion of symptomatic cases undergone influenza surveillance before and during the pandemic was 2.38% (95% CI 2.08%-2.67%) and 4.18% (95% CI 3.8%-4.52%) respectively. However, the pooled proportion of samples tested for influenza before the pandemic was 0.69% (95% CI 0.45-0.92%) and during the pandemic was 0.48% (95% CI 0.28-0.68%) when studies from Canada were excluded. The meta-analysis concludes that globally there was a decline in influenza surveillance during the COVID-19 pandemic except in Canada.
- **Spike-Induced Disturbances (SPAS*): An Analysis of Common Suspected Adverse Experiences Associated With Covid-19 Vaccines** -
This review/analysis gives a first impression of numerous adverse events related to Covid-19 vaccination, which have received little attention to date, are often unexplained, but are nevertheless very distressing. Frequently observed organ-related ADRs after Covid-19 vaccination were such of the nervous system, musculoskeletal system, gastrointestinal tract, and skin. The involvement of almost all organs in the side effect spectrum of Covid-19 vaccines demonstrates their systemic efficacy. As shown by the ADRs occurrence even after numerous days to weeks, the duration of spike production obviously lasts longer than claimed. The key role is played by the interaction between the spike subunit S1 and the membrane-bound enzyme ACE2, the receptor for SARS-CoV. Downregulation of ACE2 by spikes and following activation of RAAS can lead to numerous clinically relevant disorders, such as vasoconstriction, tissue ischemia, induction of proliferative processes, increased oxidative stress, inflammation, or coagulation disorders, as previously shown for cardiovascular reactions. It is proposed to use the collective term “SPAS” (in German: Spike ausgelöste Störungen) - spike induced disturbances for side effects based on this mode of action. The common mode of action and only slightly different frequencies of adverse events and fatal outcomes do not indicate any principal differences in adverse event profiles of the individual spike-based Covid-19 vaccines. A class-specific side effect profile can be assumed. Knowledge and awareness of the comprehensive adverse event profile of the novel Covid-19 vaccines and their potential dangerousness may improve vaccine safety.
- A cellular assay for spike/ACE2 fusion: quantification of fusion-inhibitory antibodies after COVID-19 and vaccination -
Not all antibodies against SARS-CoV-2 inhibit viral entry and hence infection. Neutralizing antibodies are more likely to reflect real immunity, however certain of these tests investigate protein/protein interaction rather than the fusion event. Viral and pseudoviral entry assays detect functionally active antibodies, however they are cumbersome and burdened by biosafety and standardization issues. We have developed a Spike/ACE2-dependant cell-to-cell fusion assay, based on a split luciferase. Hela cells stably transduced with Spike and a large fragment of luciferase were co-cultured with Hela cells transduced with ACE2 and the complementary small fragment of luciferase. Within 24h, cell fusion occured allowing the measurement of luminescence. Light emission was abolished in the absence of Spike and reduced in the presence of an inhibitor of Spike-processing proteases. Serum samples from COVID-19-negative, non-vaccinated individuals, or sera from patients at the moment of first symptoms did not lead to a significant reduction of fusion. In contrast, sera from COVID-19-positive patients as well as sera from vaccinated individuals reduced the fusion. In conclusion, we report a new method measuring fusion-inhibitory antibodies in serum, combining the advantage of a functional full Spike/ACE2 interaction with a high degree of standardization, easily allowing automation in a standard bio-safety environment.
- Tracking infectious entry routes of SARS-CoV-2 -
SARS-CoV-2 cell entry starts with membrane attachment and ends with spike-protein (S) catalyzed membrane fusion depending on two cleavage steps, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time 3D single virion tracking, we show fusion and genome penetration requires virion exposure to an acidic milieu of pH 6.2-6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2 overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2 expressing cells in the acidic milieu of the nasal cavity.
- Binding and unbinding pathways of peptide substrate on SARS-CoV-2 3CL protease -
Based on many crystal structures of ligand complexes, much study has been devoted to understanding the molecular recognition of SARS-CoV-2 3C-like protease (3CLpro), a potent drug target for COVID-19. In this research, to extend this present static view, we examined the kinetic process of binding/unbinding of an eight-residue substrate peptide to/from 3CLpro by evaluating the path ensemble with the weighted ensemble simulation. The path ensemble showed the mechanism of how a highly flexible peptide folded into the bound form. At the early stage, the dominant motion was the diffusion on the protein surface showing a broad distribution, whose centre was led into the cleft of the Chymotrypsin fold. We observed a definite sequential formation of the hydrogen bonds at the later stage occurring in the cleft, initiated between Glu166 (3CLpro) and P3_Val (peptide), followed by binding to the oxyanion hole and completed by the sequence-specific recognition at P1_Gln.
- SARS-CoV-2-neutralizing humoral IgA response occurs earlier but modest and diminishes faster compared to IgG response. -
Secretory immunoglobulin A (IgA) plays a crucial role in the mucosal immunity for preventing the invasion of the exogenous antigens, however, little has been understood about the neutralizing activity of serum IgA. Here, to examine the role of IgA antibodies against COVID-19 illnesses, we determined the neutralizing activity of serum/plasma IgG and IgA purified from previously SARS-CoV-2-infected and COVID-19 mRNA-vaccine-receiving individuals. We found that serum/plasma IgA possesses substantial but rather modest neutralizing activity against SARS-CoV-2 compared to IgG with no significant correlation with the disease severity. Neutralizing IgA and IgG antibodies achieved the greatest activity at approximately 25 and 35 days after symptom onset, respectively. However, neutralizing IgA activity quickly diminished and went down below the detection limit approximately 70 days after onset, while substantial IgG activity was observed till 200 days after onset. The total neutralizing activity in sera/plasmas of those with COVID-19 largely correlated with that in purified-IgG and purified-IgA and levels of anti-SARS-CoV-2-S1-binding IgG and anti-SARS-CoV-2-S1-binding IgA. In individuals who were previously infected with SARS-CoV-2 but had no detectable neutralizing IgA activity, a single dose of BNT162b2 or mRNA-1273 elicited potent serum/plasma neutralizing IgA activity but the second dose did not further strengthen the neutralization antibody response. The present data show that the systemic immune stimulation with natural infection and COVID-19 mRNA-vaccines elicit both SARS-CoV-2-specific neutralizing IgG and IgA response in serum, but the IgA response is modest and diminishes faster compared to IgG response.
Phase I Clinical Trial of GEN2-Recombinant COVID-19 Vaccine (CHO Cells) in Healthy People Aged 18 and Above - Condition: COVID-19 Pneumonia
Interventions: Biological: Experimental Vaccine 1; Biological: Experimental Vaccine 2; Biological: Experimental Vaccine 3; Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
COVID-19 Algorithm Treatment at Home - Condition: COVID-19
Interventions: Drug: Recommended treatment schedule; Drug: Usual care
Sponsor: Mario Negri Institute for Pharmacological Research
Not yet recruiting
Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19) - Condition: COVID-19
Interventions: Drug: Eucalyptus Oil; Drug: Standard COVID medication
Sponsors: Hasanuddin University; Ministry of Agriculture, Republic of Indonesia
Completed
Study of Oral High/Low-dose Cepharanthine Compared With Placebo in Non Hospitalized Adults With COVID-19 - Condition: Asymptomatic COVID-19
Interventions: Drug: Cepharanthine; Drug: Placebo
Sponsors: Shanghai Jiao Tong University School of Medicine; YUNNAN BAIYAO GROUP CO.,LTD
Not yet recruiting
Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island - Condition: COVID-19
Intervention: Other: telephone interview 24 months after hospitalization for Covid-19
Sponsor: Centre Hospitalier Universitaire de la Réunion
Not yet recruiting
α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19 - Condition: COVID-19
Intervention: Other: Real-time Quaking-Induced Conversion (RT-QuIC)
Sponsor: Medical University Innsbruck
Recruiting
Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults - Condition: COVID-19 Vaccines
Interventions: Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech); Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
Sponsors: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network
Not yet recruiting
Immunogenicity and Safety of a Third Dose of COVID-19 Vaccine(Vero Cell), Inactivated in the Elderly - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine (Vero cell), Inactivated
Sponsor: Sinovac Life Sciences Co., Ltd.
Active, not recruiting
Efficacy, Safety and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell)(Recov) - Condition: COVID-19
Interventions: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: Placebo
Sponsor: Jiangsu Rec-Biotechnology Co., Ltd.
Not yet recruiting
Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain
Sponsor: Sinovac Biotech (Hong Kong) Limited
Not yet recruiting
A Phase 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19 - Condition: COVID-19
Interventions: Biological: RQ3013; Biological: Comirnaty
Sponsors: Walvax Biotechnology Co., Ltd.; Shanghai RNACure Biopharma Co., Ltd.
Not yet recruiting
Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb) - Conditions: COVID-19 Acute Respiratory Distress Syndrome; COVID-19
Interventions: Drug: Plerixafor 20 MG/ML [Mozobil]; Other: Placebo
Sponsor: 4Living Biotech
Not yet recruiting
Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19 - Conditions: COVID-19; Type 2 Diabetes Mellitus
Intervention: Other: Aerobic and Relaxation Exercises
Sponsor: Bozyaka Training and Research Hospital
Active, not recruiting
Long Haul COVID Rehabilitation & Recovery Research Program - Condition: Long Haul COVID or Post Acute Sequella of COVID - PASC (U09.9)
Intervention: Other: Virtual vs On Site Pulmonary Rehabilitation
Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Recruiting
Inhibition of Bradykinin in COVID-19 Infection With Icatibant - Condition: SARS CoV 2 Infection
Interventions: Drug: Icatibant; Drug: 0.9% Sodium Chloride Injection
Sponsors: Belfast Health and Social Care Trust; Queen’s University, Belfast
Recruiting
Prevalence of alcohol-tolerant and antibiotic-resistant bacterial pathogens on public hand sanitizer dispensers - CONCLUSION: HSDs serve as potential breeding grounds for dissemination of pathogens and antibiotic resistance across unknowing users. Proper HSD maintenance will ensure protection of public health and sustainable use of sanitizing alcohols, to prevent emergence of alcohol-resistant pathogens.
Risk stratification models for stroke in patients hospitalized with COVID-19 infection - CONCLUSIONS: We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.
The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition - Highly pathogenic human coronaviruses (CoV) including SARS-CoV, MERS-CoV and SARS-CoV-2 have emerged over the past two decades, resulting in infectious disease outbreaks that have greatly affected public health. The CoV surface spike (S) glycoprotein mediates receptor binding and membrane fusion for cell entry, playing critical roles in CoV infection and evolution. The S glycoprotein is also the major target molecule for prophylactic and therapeutic interventions, including neutralizing…
Inhibition of SARS-CoV-2 pathogenesis by potent peptides designed by the mutation of ACE2 binding region - The outbreak of COVID-19 has resulted in millions of deaths. Despite all attempts that have been made to combat the pandemic, the re-emergence of new variants complicated SARS-CoV-2 eradication. The ongoing global spread of COVID-19 demands the incessant development of novel agents in vaccination, diagnosis, and therapeutics. Targeting receptor-binding domain (RBD) of spike protein by which the virus identifies host receptor, angiotensin-converting enzyme (ACE2), is a promising strategy for…
Discovery of novel SARS-CoV-2 inhibitors targeting the main protease Mpro by virtual screenings and hit optimization - Two years after its emergence, SARS-CoV-2 still represents a serious and global threat to human health. Antiviral drug development usually takes a long time and, to increase the chances of success, chemical variability of hit compounds represents a valuable source for the discovery of new antivirals. In this work, we applied a platform of variably oriented virtual screening campaigns to seek for novel chemical scaffolds for SARS-CoV-2 main protease (M^(pro)) inhibitors. The study on the…
Breaking boundaries: Pan BETi disrupt 3D chromatin structure, BD2-selective BETi are strictly epigenetic transcriptional regulators - BACKGROUND: Bromodomain and extraterminal proteins (BETs) are more than just epigenetic regulators of transcription. Here we highlight a new role for the BET protein BRD4 in the maintenance of higher order chromatin structure at Topologically Associating Domain Boundaries (TADBs). BD2-selective and pan (non-selective) BET inhibitors (BETi) differentially support chromatin structure, selectively affecting transcription and cell viability.
Conjugation with 8-arm PEG and CRM197 enhances the immunogenicity of SARS-CoV-2 ORF8 protein - Safe and effective vaccines are urgently needed to combat the COVID-19 pandemic. However, the SARS-CoV-2 variants raise concerns about the effectiveness of vaccines. As a SARS-CoV-2 antigen target, ORF8 strongly inhibits the IFN-β and NF-κB-responsive promoter, and can be potentially used for the development of SARS-CoV-2 vaccine. However, it is necessary to improve the immunogenicity of ORF8 by adjuvants or delivery systems. CRM(197) was a carrier protein with the ability to activate T helper…
Bovine colostrum-derived antibodies against SARS-CoV-2 show great potential to serve as prophylactic agents - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is ongoing. One of the mechanisms by which neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2-specific NAb…
Commentary: University Technology Transfer Has Made a Significant Contribution to Fighting COVID-19 while Ensuring Global Access - This paper reviews the response by public sector research organizations and their technology transfer offices to the COVID-19 pandemic. It shows that leading universities and technology transfer associations quickly enacted licensing principles for the duration of the pandemic to maximize availability and minimize delays in translating public sector research institutes’ (PSRIs’) COVID-19 inventions to the public - in both the developed and the developing world - while waiving payment of…
Potential therapeutic effects of Ivermectin in COVID-19 - COVID-19 is a critical pandemic that affected communities around the world, and there is currently no specific drug treatment for it. The virus enters the human cells via spikes and induces cytokine production and finally arrests the cell cycle. Ivermectin shows therapeutic potential for treating COVID-19 infection based on in vitro studies. Docking studies have shown a strong affinity between Ivermectin and some virulence factors of COVID-19. Notably, clinical evidence has demonstrated that…
Coronavirus Disease 2019 Vaccine Booster Effects Are Seen in Human Milk Antibody Response - Infants remain at high risk for severe coronavirus disease 2019 (COVID-19). Human milk contains high levels of protective SARS CoV-2 specific antibodies post-infection and primary vaccine series, but levels decline over time. We hypothesized that the COVID-19 booster vaccine augment antibody production and the protection afforded to human milk-fed infants. We prospectively enrolled pregnant or lactating mothers planning to receive COVID-19 vaccination. We measured human milk IgG, IgA, and IgM…
Molecular Modeling and Simulation Analysis of Antimicrobial Photodynamic Therapy Potential for Control of COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the host cells by binding the viral surface spike glycoprotein (SG) to angiotensin-converting enzyme 2. Since antiviral photodynamic therapy (aPDT) has been described as a new method for inhibiting viral infections, it is important to evaluate whether it can be used as a photoactivated disinfectant to control COVID-19. In this in silico study, SARS-CoV-2-SG was selected as a novel target for curcumin as a photosensitizer…
Transient Complete Recovery of Chronic Refractory Idiopathic Thrombocytopenic Purpura after Treatment with Monoclonal Antibody Targeting SARS-CoV-2 Spike Protein - Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenic purpura, is an immune-mediated acquired disease characterized by transient or persistent decrease of the platelet count due to autoimmune-related destruction of platelets. Therapy for ITP relies on competing and inhibiting the autoantibody binding and destruction (intravenous immunoglobulin and anti-D immunoglobulin and spleen tyrosine kinase (Syk) inhibitor fostamatinib), augmenting platelet production…
Development and Validation of an HPLC-UV Method for the Quantification of 4’-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug-Drug Interaction in Rat Liver Microsomes - Salicylic acid is a key compound in nonsteroidal anti-inflammatory drugs that has been recently used for preventing the risk of hospitalization and death among COVID-19 patients and in preventing colorectal cancer (CRC) by suppressing two key proteins. Understanding drug-drug interaction pathways prevent the occurrence of adverse drug reactions in clinical trials. Drug-drug interactions can result in the variation of the pharmacodynamics and pharmacokinetic of the drug. Inhibition of the…
Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle - The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities….