- Four points regarding reproducibility and external statistical validity: a comment on Walter et al. -
Walter et al. (2021) present phase 1–2–3 trial data that show two doses of the BNT162b2 (Pfizer–BioN-Tech) Covid-19 vaccine were safe and effective in children aged 5–11 years. Given that millions of children in this age group are receiving the paediatric Pfizer COVID-19 vaccine, that there are potential risks, and that the balance of benefits over potential risks is more limited in children compared to adults due to low rates of serious disease (ATAGI 2021), gold standards ought to be applied to supporting data in terms of placebo-controlled disease endpoint efficacy trials, safety databases large enough to detect adverse events, and appropriate data sharing to enable reproduction and scrutiny of results. Four points are worthy of attention regarding the reproducibility and external statistical validity of the analysis reported in Walter et al. (2021). ‘External validity’ refers to the extent to which conclusions drawn from the data (and statistical tests thereof) are likely to correspond to, or be generalisable to, the real world (Campbell 1957). ‘Reproducibility’ refers to the ability of independent researchers to draw the same conclusions from the data (Kass et al. 2016).
- Investigating the role of binding free energy, binding affinity and antibody escape in the evolution of SARS-CoV-2 spike protein. -
SARS-CoV-2 is considered a pandemic virus and presents a major strain on public health globally. SARS-CoV-2 infects mammalian cells by binding to its receptor, ACE2 which is mediated by the viral spike glycoprotein, specifically the receptor binding domain (RBD) within the spike protein. Recent development of vaccines against SARS-CoV-2 spike protein are currently the best strategy to reduce morbidity and mortality from infection. Like all viruses, SARS-CoV-2 evolves which may result in mutations which are benign or alter its viral fitness. The evolution of SARS-CoV-2 may increase the virulence, possibly by increasing the infectivity of the virus through strengthening the binding of the RBD to ACE2 or enabling the virus to evade naturally or vaccine induced immune responses. To address the need to characterise the evolution of SARS-CoV-2, this study has compared SARS-CoV-2 sequences globally to the Wuhan reference strain at different time points. Additionally, by assigning scores to sequence data, which quantify each sequences binding strength to ACE2 and ability to evade patient derived antibodies, we have demonstrated that over time SARS-CoV-2 has evolved in less than one year to increase its ability to evade antibodies and increase the binding free energy between the RBD and ACE2.
- Host independent deletion hotspots in the SARS-CoV-2 genome -
SARS-CoV-2 infects a wide range of hosts in varying degrees. The RNA genome of SARS-CoV-2 makes it prone to mutations. Advantageous mutations help the virus to evolve and the virus maintains such mutations across species. Here in this study, all non-human hosts-derived SARS-CoV-2 genomic sequences from the GISAID database were analyzed, and identified several deletion hotspots, which are maintained by the virus, across various host species, indicating their important role in the virus evolution. Several of these deletion hotspots are also found in human-derived SARS-CoV-2 genomic sequences. These deletion hotspots have the potential to affect the pathogenicity and virulence of the virus and have a role in molecular and serological diagnostics. Potentially, they can lead to immune escape, resulting in vaccine failure and drug-resistant variants.
- Diet Induced Obesity and Diabetes Enhance Mortality and Reduces Vaccine Efficacy for SARS-CoV-2 -
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. As of October 2022, there have been over 625 million confirmed cases of COVID-19, including over 6.5 million deaths. Epidemiological studies have indicated that comorbidities of obesity and diabetes mellitus are associated with increased morbidity and mortality following SARS-CoV-2 infection. We determined how the comorbidities of obesity and diabetes affect morbidity and mortality following SARS-CoV-2 infection in unvaccinated and adjuvanted spike nanoparticle (NVX-CoV2373) vaccinated mice. We find that obese/diabetic mice infected with SARS-CoV-2 have increased morbidity and mortality compared to age matched normal mice. Mice fed a high-fat diet (HFD) then vaccinated with NVX-CoV2373 produce equivalent neutralizing antibody titers to those fed a normal diet (ND). However, the HFD mice have reduced viral clearance early in infection. Analysis of the inflammatory immune response in HFD mice demonstrates a recruitment of neutrophils that was correlated with increased mortality and reduced clearance of the virus. This model recapitulates the increased disease severity associated with obesity and diabetes in humans with COVID-19 and is an important comorbidity to study with increasing obesity and diabetes across the world.
- The impact of the ABO/Rh blood group on susceptibility and severity among COVID-19 patients in Luanda, Angola -
SARS-CoV-2 is a public health concern worldwide. Identification of biological factors that could influence transmission and worsen the disease has been the subject of extensive investigation. Herein, we investigate the impact of the ABO/Rh blood group on susceptibility and severity among COVID-19 patients in Luanda, Angola. This was a multicentric cohort study conducted with 101 COVID-19 patients. Chi-square and logistic regression were calculated to check factors related to the worsening of the disease and deemed significant when p<0.05. Blood type O (51.5%) and Rh-positive (93.1%) were the most frequent. Patients from blood type O had a high risk to severe disease [OR: 1.33 (95% CI: 0.42 - 4.18), p=0.630] and hospitalization [OR: 2.59 (95% CI: 0.84 - 8.00), p=0.099]. Also, Rh-positive blood type presented a high risk for severe disease (OR: 10.6, p=0.007) and hospitalization (OR: 6.04, p=0.026). We find a high susceptibility, severity, hospitalization, and mortality, respectively, among blood group O and Rh-positive patients, while blood group AB presented a low susceptibility, severity, hospitalization, and mortality, respectively. Our findings add to the body of evidence suggesting that ABO/Rh blood groups play an important role in the course of SARS-CoV-2 infection.
- COVID-19 outbreaks in child care facilities Alberta from March 2020 to December 31, 2021 -
Background: Children attending child care are vulnerable to SARS CoV-2 infection, and mitigation measures like masking, distancing, enhanced hygiene are not feasible for this population. Describing outbreak growth during the COVID-19 pandemic in child care centres may provide insight in how to best mitigate the risks of COVID-19 and other infectious diseases in these settings. Objective: To describe the characteristics of child care outbreaks and associated cases in Alberta. Methods: Our observational study used data on outbreaks and associated cases tracked through the Alberta Health Services Communicable Disease Outbreak Management database. We included all COVID-19 outbreaks opened in child care facilities in the province (March 2020 to December 31, 2021). We compared the characteristics of outbreaks and cases during each wave of the pandemic. Outcome: 841 outbreaks were opened in Alberta, including 4613 cases (70.2% in children and 29.8% adults). Outbreaks averaged 5.5 cases per outbreak, and the average duration of time between symptoms starting in the first and last case was 9.7 days. The likely index was a child in 55.1% of outbreaks. Conclusions: Adults are a high proportion of cases compared to their proportion of the population at child care facilities, and have consistently higher attack rates than children. Children have the highest attack rates when other children are the index case. Measures shown to be effective in other settings to reduce spread among adults can be implemented here, such as vaccination, strictly enforcing exclusion of those symptomatic, and facilitating rapid testing.
- From Cold to Killer: How SARS-CoV-2 Evolved without Hemagglutinin Esterase to Agglutinate and Then Clot Blood Cells -
The role of vascular occlusion in the morbidities, pulmonary and systemic, of COVID-19 has received increasing focus. Histological studies of lung tissue from COVID-19 patients have found extensively damaged endothelium of capillaries adjoining relatively intact alveoli, corresponding to hypoxemia accompanying normal breathing mechanics in such patients. Essential to the study of vascular occlusion in COVID-19 are viral properties dating back to studies of Jonas Salk in the 1940s that have been positively established for SARS-CoV-2. First, SARS-CoV-2 binds to red blood cells (RBCs) in vitro and also clinically in COVID-19 patients. Second, although fusion and replication of SARS-CoV-2 occur via ACE2, such hemagglutinating viruses initially attach to infective targets and clump with blood cells via much more abundantly distributed glycoconjugate binding sites, notably those tipped with sialic acid (SA). SARS-CoV-2, in particular, attaches to these glycan binding sites. Third, certain enveloped viruses express an enzyme, hemagglutinin esterase (HE), that counteracts viral-RBC clumping. Notably, among betacoronaviruses, the common cold strains express HE while SARS-CoV-2, SARS-CoV-1 and MERS, the virulent strains, do not. The hemagglutinating properties of SARS-COV-2 establish a framework for “catch and clump” induction of microvascular occlusion proposed here. Ultramicroscopic studies of tissues from COVID-19 patients indicate a key role for hemagglutination early and mid-course in COVID-19, before such clumps develop into clots via the coagulation cascade.
- The Impact of the Covid-19 Pandemic on the Legal Concept of Visas in Indonesia -
The Covid-19 pandemic that has been going on globally since March 2020 has led to the universal closure of national borders. The exponential spread of the Covid-19 virus has resulted in a new phenomenon in the immigration field: stranded foreigners. To avoid the continued access of these stranded foreigners, Indonesian immigration issued a series of visa regulations. This study aims to analyse the impact of the Covid-19 pandemic on the concept of visa law applicable in Indonesia by existing formal law. This research uses a normative method with a conceptual approach, namely by identifying existing principles or doctrinal views and then generating new ideas. The concepts and theories used in this research are the rules of law concept with an analytical knife in the form of a hierarchy of laws and regulations theory and the theory of sovereignty. The results show that there is a shift in the concept of visa law in Indonesia as a result of the Covid-19 pandemic. In the theoretical study, it is known that this shift in the idea of visa law has ruled out the visa doctrine that has been regulated in Indonesian immigration law. However, the principle of relative sovereignty that respects the principles of international law is the justification for changing the concept of visa law in Indonesia during the Covid-19 pandemic.
- Determinants and Mechanisms of the Low Fusogenicity and Endosomal Entry of Omicron Subvariants -
The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation, as shown by increased molecular interactions in structural modeling as well as reduced S1 shedding. Importantly, the H655Y mutation also determines the low fusogenicity and high dependence on the endosomal entry pathway of other Omicron subvariants, including BA.2, BA.2.12.1, BA.4/5 and BA.2.75. These results uncover mechanisms governing Omicron subvariant entry and provide insights into altered Omicron tissue tropism and pathogenesis.
- Comparative Mutagenesis of SARS-CoV-2 Nonstructural Proteins (NSPs) Across Variants: The Case for RdRp as a Therapeutic Target -
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenicity has been studied extensively from the perspective of structural (S, E, M, N) proteins for purposes in vaccine development. The virus’s nonstructural protein (nsp) components are less characterized, and demonstrate significant potential in efforts to develop novel therapeutic agents. NSP 7, 8, and 12, formed from the cleavage of pp1a and pp1ab polyproteins, comprise the viral replicase (RdRp) complex, the site for the mechanism of action of Remdesivir. Presented herein is a phylogenetic analysis for the evolution of SARS-CoV-2 replicase components between variant and related coronaviruses with the aim to delineate its current and long-term efficacy as a drug target.
- Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes. -
SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed and open. The locked conformations feature tightly packed trimers with structural elements incompatible with RBD in “up” position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably due to their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. Intriguingly, locked conformations were the only conformations captured for S proteins of bat and pangolin origin SARS-related coronaviruses. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures to other available spike structures of Sarbecoviruses to identify conserved features and discuss their possible functions.
- SARS-CoV-2 multi-antigen protein microarray for detailed characterization of antibody responses in COVID-19 patients -
Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target multiple epitopes on different domains of the spike protein, and other SARS-CoV-2 proteins. We developed a SARS-CoV-2 multi-antigen protein microarray with the nucleocapsid, spike and its domains (S1, S2), and variants with single (D614G, E484K, N501Y) or double substitutions (N501Y/Deletion69/70), allowing a more detailed high-throughput analysis of the antibody repertoire following infection. The assay was demonstrated to be reliable and comparable to ELISA. We analyzed antibodies from 18 COVID-19 patients and 12 recovered convalescent donors. S IgG level was higher than N IgG in most of the COVID-19 patients, receptor-binding domain of S1 showed high reactivity, but no antibodies were detected against heptad repeat domain 2 of S2. Furthermore, antibodies were detected against S variants with single and double substitutions in COVID-19 patients who were infected with SARS-CoV-2 early in the pandemic. Here we demonstrated that SARS-CoV-2 multi-antigen protein microarray is a powerful tool for detailed characterization of antibody responses, with potential utility in understanding the disease progress and assessing current vaccines and therapies against evolving SARS-CoV-2.
- Serology assays used in SARS-CoV-2 seroprevalence surveys worldwide: a systematic review and meta-analysis of assay features, testing algorithms, and performance -
Background: Many SARS-CoV-2 serological assays were rapidly developed during the COVID-19 pandemic. However, differences in detection mechanism limit the comparability of assay outputs. Methods: As part of the SeroTracker global living systematic review of SARS-CoV-2 seroprevalence studies, we collated serological assays used in serosurveys between January 1, 2020 and November 19, 2021. We mapped performance metrics to the manufacturer, third-party head-to-head, and independent group evaluations, comparing the assay performance data using a mixed-effect beta regression model. Results: Among 1807 serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). Third-party and independent evaluations indicated that manufacturers overstated the Sn. of their assays by 5.4% and 2.8%, and Sp. by 6.3% and 1.2%. We found in simulations that inaccurate Sn. and Sp. can substantially bias seroprevalence estimates corrected for assay performance. Conclusions: The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on testing population. To achieve precise population estimates and to ensure comparability, serosurveys should select assays with strong, independently validated performance and adjust seroprevalence estimates based on assured performance data.
- Stability of SARS-CoV-2 spike antigens against mutations -
Modern health care needs preventive vaccines and therapeutic treatments with stability against pathogen mutations to cope with current and future viral infections. At the beginning of the COVID-19 pandemic, our analytic and predictive tool identified a set of eight short SARS-CoV-2 S-spike protein epitopes that had the potential to persistently avoid mutation. Here a combination of genetic, Systems Biology and protein structure analyses confirm the stability of our identified epitopes against viral mutations. Remarkably, this research spans the whole period of the pandemic, during which 93.9% of the eight peptides remained invariable in the globally predominant 43 circulating variants, including Omicron. Likewise, the selected epitopes are conserved in 97% of all 1,514 known SARS-CoV-2 lineages. Finally, experimental analyses performed with these short peptides showed their specific immunoreactivity. This work opens a new perspective on the design of next-generation vaccines and antibody therapies that will remain reliable against future pathogen mutations.
- The SARS-CoV-2 spike N-terminal domain engages 9-O-acetylated α2-8-linked sialic acids -
SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the spike protein contains a C-terminal receptor-binding domain (RBD) and an N-terminal domain (NTD). The NTD of other coronaviruses includes a glycan-binding cleft. However, for the SARS-CoV-2 NTD protein-glycan binding was only observed weakly for sialic acids with highly sensitive methods. Amino acid changes in the NTD of Variants of Concern (VoC) shows antigenic pressure, which can be an indication of NTD-mediated receptor binding. Trimeric NTD proteins of SARS-CoV-2, Alpha, Beta, Delta, and Omicron did not reveal a receptor binding capability. Unexpectedly, the SARS-CoV-2 Beta subvariant strain (501Y.V2-1) NTD binding to Vero E6 cells was sensitive to sialidase pretreatment. Glycan microarray analyses identified a putative 9-O-acetylated sialic acid as a ligand, which was confirmed by catch-and-release ESI-MS, STD-NMR analyses, and a graphene-based electrochemical sensor. The Beta (501Y.V2-1) variant attained an enhanced glycan binding modality in the NTD with specificity towards 9-O-acetylated structures, suggesting a dual-receptor functionality of the SARS-CoV-2 S1 domain, which was quickly selected against. These results indicate that SARS-CoV-2 can probe additional evolutionary space, allowing binding to glycan receptors on the surface of target cells.
A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir - Condition: COVID-19
Interventions: Drug: nirmatrelvir; Drug: ritonavir; Drug: placebo for nirmatrelvir
Sponsor: Pfizer
Not yet recruiting
Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell) - Condition: COVID-19
Interventions: Biological: Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell); Biological: Inactivated COVID-19 vaccine (Vero Cell)
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; First Affiliated Hospital Bengbu Medical College
Active, not recruiting
A Phase III Study to Evaluate Immunogenicity and Safety of COVID-19 Vaccine EuCorVac-19 in Healthy Adults - Condition: COVID-19
Interventions: Biological: EuCorVac-19; Biological: ChAdOx1
Sponsor: EuBiologics Co.,Ltd
Recruiting
COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement - Condition: COVID-19 Pandemic
Intervention: Behavioral: Tri-City COVID Attitudes Study
Sponsor: University of Kansas Medical Center
Recruiting
JT001 (VV116) for the Treatment of COVID-19 - Condition: Mild to Moderate COVID-19
Interventions: Drug: JT001; Drug: Placebo
Sponsors: Shanghai Vinnerna Biosciences Co., Ltd.; Sponsor GmbH
Not yet recruiting
VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination - Conditions: Immunization; Infection; Pregnancy Related; COVID-19
Interventions: Behavioral: VAX-MOM COVID-19 Intervention; Other: Standard of Care
Sponsors: University of Rochester; Centers for Disease Control and Prevention; University of California, Los Angeles
Not yet recruiting
Respiratory Muscles After Inspiratory Muscle Training After COVID-19 - Conditions: COVID-19; Diaphragm Injury
Intervention: Device: Inspiratory Muscle Training (IMT)
Sponsors: RWTH Aachen University; Philipps University Marburg Medical Center
Recruiting
COVID-19 Simulation Education on Nursing Students - Conditions: COVID-19 Pandemic; Simulation of Physical Illness
Interventions: Behavioral: Simulation training; Other: Control Group
Sponsor: Mehmet Akif Ersoy University
Completed
COVID-19 Booster Dose Reminder/Recall for Adolescents - Condition: COVID-19 Vaccines
Intervention: Behavioral: Reminder/Recall Sent Via Preferred Method of Communication
Sponsor: Marshfield Clinic Research Foundation
Active, not recruiting
COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions: SARS-CoV2 Infection; COVID-19
Interventions: Device: iCura COVID-19 Antigen Rapid Home Test; Device: RT-PCR Test
Sponsors: MP Biomedicals, LLC; EDP Biotech
Completed
COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability - Conditions: Sars-CoV-2 Infection; COVID-19
Intervention: Device: Rapid SARS-CoV-2 Antigen Test
Sponsors: MP Biomedicals, LLC; EDP Biotech
Completed
Exploratory Clinical Study to Evaluation of the Safety and Immunogencity of Bivalent Vaccine V-01D-351 - Condition: COVID-19 Pandemic
Interventions: Biological: V-01D-351; Biological: CoronaVac
Sponsor: Livzon Pharmaceutical Group Inc.
Active, not recruiting
Safety and Immunogenicity of AdCLD-CoV19-1 OMI as a Booster: A SARS-CoV-2 (COVID-19) Preventive Vaccine - Conditions: COVID-19; Vaccines
Interventions: Biological: AdCLD-CoV19-1 OMI (Part A); Biological: AdCLD-CoV19-1 OMI (Part B); Other: Placebo (Part B)
Sponsor: Cellid Co., Ltd.
Active, not recruiting
Safety and Dosage of a Computerized Cognitive Training Program for Cognitive Dysfunction After COVID-19 - Conditions: Post-Acute COVID-19; Post Acute COVID-19 Syndrome; Cognitive Dysfunction; Cognitive Impairment
Intervention: Behavioral: CCT Long COVID
Sponsor: Universidad Antonio de Nebrija
Not yet recruiting
The Effect of Different Masks Used by Pregnant Women on Vital Signs and Non Stress Test During The COVID-19 - Conditions: Covid-19; Pregnant; Fetus; Mask
Intervention: Behavioral: Single surgical mask group, Double surgical mask group, N95 mask group
Sponsor: Bozok University
Completed
DNA damage contributes to age-associated differences in SARS-CoV-2 infection - Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to disproportionately affect older individuals. How aging processes affect SARS-CoV-2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS-CoV-2 infection in vitro and in vivo. SARS-CoV-2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and…
Effects of natural polymorphisms in SARS-CoV-2 RNA-dependent RNA polymerase on its activity and sensitivity to inhibitors in vitro - SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is the key enzyme required for viral replication and mRNA synthesis. RdRp is one of the most conserved viral proteins and a promising target for antiviral drugs and inhibitors. At the same time, analysis of public databases reveals multiple variants of SARS-CoV-2 genomes with substitutions in the catalytic RdRp subunit nsp12. Structural mapping of these mutations suggests that some of them may affect the interactions of nsp12 with its cofactors…
Xuanfei Baidu Formula attenuates LPS-induced acute lung injury by inhibiting the NF-κB signaling pathway - CONCLUSION: This study identified the potential practical components of XFBD, combined with network pharmacology and experimental validation to demonstrate that XFBD can alleviate lung injury caused by ALI by inhibiting the NF-κB signaling pathway.
Does income inequality reshape the environmental Kuznets curve (EKC) hypothesis? A nonlinear panel data analysis - The COVID-19 pandemic has further increased income inequality. This work is aimed to explore the impact of income inequality on the environmental Kuznets curve (EKC) hypothesis. To this end, income inequality is set as the threshold variable, economic growth is set as the explanatory variable, while carbon emission is set as the explained variable, and the threshold panel model is developed using the data of 56 countries. The empirical results show that income inequality has changed the…
Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibit the infection of SARS-CoV-2 variants and syncytium formation - The continuous emergence of SARS-CoV-2 variants prolongs COVID-19 pandemic. Although SARS-CoV-2 vaccines and therapeutics are currently available, there is still a need for development of safe and effective drugs against SARS-CoV-2 and also for preparedness for the next pandemic. Here, we discover that astersaponin I (AI), a triterpenoid saponin in Aster koraiensis inhibits SARS-CoV-2 entry pathways at the plasma membrane and within the endosomal compartments mainly by increasing cholesterol…
Role of CCL2/CCR2 axis in the pathogenesis of COVID-19 and possible Treatments: All options on the Table - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is cause of the novel coronavirus disease (COVID-19). In the last two years, SARS-CoV-2 has infected millions of people worldwide with different waves, resulting in the death of many individuals. The evidence disclosed that the host immune responses to SARS-CoV-2 play a pivotal role in COVID-19 pathogenesis and clinical manifestations. In addition to inducing antiviral immune responses, SARS-CoV-2 can also cause dysregulated…
Trim69 is a microtubule regulator that acts as a pantropic viral inhibitor - Through a screen that combines functional and evolutionary analyses, we identified tripartite motif protein (Trim69), a poorly studied member of the Trim family, as a negative regulator of HIV-1 infection in interferon (IFN)-stimulated myeloid cells. Trim69 inhibits the early phases of infection of HIV-1, but also of HIV-2 and SIV(MAC) in addition to the negative and positive-strand RNA viruses vesicular stomatitis virus and severe acute respiratory syndrome coronavirus 2, with magnitudes that…
Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS - CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.
In-silico structural inhibition of ACE-2 binding site of SARS-CoV-2 and SARS-CoV-2 Omicron spike protein by lectin antiviral dyad system to treat COVID-19 - Spike glycoprotein of SARS-CoV-2 binds ACE-2 receptors via its receptor-binding-domain (RBD) and mediates virus-to-host cell fusion. Recently emerged omicron variant of SARS-CoV-2 possess around 30 mutations in spike protein where N501Y tremendously increases viral infectivity and transmission. Lectins interact with glycoproteins and mediate innate immunity displaying antiviral, antibacterial and anticarcinogenic properties. In this study, we analysed the potential of lectin, and lectin-antibody…
Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2 - New pathogens responsible for novel human disease outbreaks in the last two decades are mainly the respiratory system viruses. Not different was the last pandemic episode, caused by infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the extensively explored targets, in the recent scientific literature, as a possible way for rapid development of COVID-19 specific drug(s) is the interaction between the receptor-binding domain of the virus’ spike (S) glycoprotein…
Atovaquone for treatment of COVID-19: A prospective randomized, double-blind, placebo-controlled clinical trial - Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (M^(pro)), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to…
Achieving sustainability: Determinants of conscious green purchasing behavior during the COVID-19 pandemic - The COVID-19 pandemic has spread worldwide, resulting in crises in public health and sustainable development. Aimed at understanding the determinants of conscious green purchasing behavior (GPB), this paper developed a comprehensive framework linking the moderating effect of negative environmental affective reactions (NEAR) to COVID-19 based on the S-O-R paradigm. Using randomly selected urban residents from China’s Yangtze River Delta and Bohai Rim regions, the empirical study was conducted…
Antiviral Effects of Heparan Sulfate Analogue-Modified Two-Dimensional MXene Nanocomposites on PRRSV and SARS-CoV-2 - Due to the worldwide impact of viruses such as SARS-CoV-2, researchers have paid extensive attention to antiviral reagents against viruses. Despite extensive research on two-dimensional (2D) transition metal carbides (MXenes) in the field of biomaterials, their antiviral effects have received little attention. In this work, heparan sulfate analogue (sodium 3-mercapto-1-propanesulfonate, MPS) modified 2D MXene nanocomposites (Ti(3)C(2)-Au-MPS) for prevention of viral infection are prepared and…
The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients - Vaccination against SARS-CoV-2 using mRNA-based vaccines has been highly recommended for fragile subjects, including myelofibrosis patients (MF). Available data on the immune responsiveness of MF patients to mRNA SARS-CoV-2 vaccination, and the impact of the therapy with the JAK inhibitor ruxolitinib, are still fragmented. Here, we profile the spike-specific IgG and memory B-cell response in MF patients, treated or not with ruxolitinib, after the second and the third dose of SARS-CoV-2 BNT162b2…
The impact of platelets on pulmonary microcirculation throughout COVID-19 and its persistent activating factors - Patients with COVID-19 often have hypoxemia, impaired lung function, and abnormal imaging manifestations in acute and convalescent stages. Alveolar inflammation, pulmonary vasculitis, and thromboembolism synergistically damage the blood-air barrier, resulting in increased pulmonary permeability and gas exchange disorders. The incidence of low platelet counts correlates with disease severity. Platelets are also involved in the impairment of pulmonary microcirculation leading to abnormal lung…