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190 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>24 September, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Does polyethylene glycol, used as an excipient at mRNA-based (Moderna, Pfizer) vaccines, cause an increase in the frequency of epilepsy in PWE?</strong> -
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PEGs, also known as polyethylene glycol, are hydrophilic polymers of various diameters made up of repeated (-CH2-CH2-O-) units and are frequently used in commercial and medical applications like cosmetics, and pharmaceutical preparations and now increase in drug development but the concern about antibodies against PEGs is producing (1) PEGs (PEGs2000) are used as excipients in mRNA-based vaccines like Moderna and Pfizer (2) it is utilized in these vaccines to encapsulate the SLNPs, polyethylene glycol (PEG), which has been identified as the main culprit for this anaphylactic reactions4,5. PEG is used in a wide variety of additional products6, including cosmetics, meals, and pharmaceutical preparations. Its action is essential for preserving the colloidal stability of nanoparticles in biological fluids as well as for lowering the amount of uptake by filter organs, which increases the effectiveness and safety of the particles after vaccination. (3). One of the most prevalent neurological conditions, epilepsy is linked to higher morbidity and mortality rates. PWE who aspirate during seizures have a higher chance of developing pneumonia, and infections can make their PWE’s seizure symptoms worse. Patients with particular epilepsy syndromes who take immunosuppressive medications (such as those with tuberous sclerosis complex or autoimmune encephalitis) must also be regarded as “at risk.” PWE is also more likely to have comorbid conditions, which increases their chance of developing a severe SARS-CoV-2 infection. (4). In a study for colonoscopic screening using PEG as safe more than sodium, the study reported 2 cases of increased frequency of epilepsy attacks on two women who were admitted with generalized tonic-clonic seizures induced by precolonoscopic PEG preparation because of PEG effect on fluids and hyponatremia-induced epilepsy, Electrolyte solutions containing PEG have been linked to seizure activity and/or unconsciousness. Low serum osmolality and irregular electrolytes were linked to the seizure cases. Patients having a history of seizures or a tendency toward them, as well as those with known or suspected hyponatremia, should receive therapy with these drugs with caution (5) Numerous research and evaluations found no evidence linking vaccines to afebrile seizures, and they concluded that immunizations do not cause the beginning of epilepsy [6]. In patients in our cohort who grew more prone to seizures post vaccination but did not have a simultaneous fever, this finding raises doubts about the direct impact of immunization, even though these patients had more serious epilepsy with less control than our multivariate analysis did confirm that seizures frequency is only influenced by one component. The frequency pattern of pre-vaccine seizures was getting worse consequently, it is conceivable to imagine that immunization was an immediate contributing factor in altering seizure frequency, in actuality, the patients who deteriorated were affected by epilepsy that is more severe and poorly controlled. (7) According to several observational studies, individuals with epilepsy (PWE) experienced worsening seizure control during the COVID-19 pandemic. (8-13) An observational study by Isabel Martinez-Fernandez shows Seizure frequency increased after vaccination in 6.2% of people with epilepsy. 6.2% of PWE saw a meaningful increase in seizure frequency after receiving the covid-19 vaccine and in 61.5% of these cases, other probable causes were also present, the causes of worsening seizures are distinct from immunization were identifiable, and patients with a higher risk of seizures and those who had an aggravation after receiving the covid-19 immunization monthly epilepsy. (14) Understanding that PEG is immunogenic and antigenic is important. More thorough investigations are necessary to thoroughly assess the effect of anti-PEG antibodies on PEG conjugates. The chance of experiencing potential adverse effects is increased by the growing usage of PEG and PEGylated therapeutic proteins. First off, side products created durin
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🖺 Full Text HTML: <a href="https://osf.io/p8kxj/" target="_blank">Does polyethylene glycol, used as an excipient at mRNA-based (Moderna, Pfizer) vaccines, cause an increase in the frequency of epilepsy in PWE?</a>
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<li><strong>Can long-term post-COVID-19 fainting syndrome explain why a US artist swimmer Anita Alvarez has recurrent fainting attacks after diving during a swimming competition? Does interleukin-6 play a role?</strong> -
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At the 19th FINA (Fédération Internationale De Natation.) World Aquatic Championships were held in Budapest, Hungary, American swimmer Anita Alvarez lost consciousness, experienced recurrent fainting attacks after diving during a swimming competition, and had to be pulled from the bottom of the pool by her coach. And this happens for the second time (1) Five (0.6%) of the 789 elite athletes in an observational study who tested positive for COVID-19 had CMR evidence of inflammatory cardiac disease (myocarditis or pericarditis) (2) Concern has been expressed by a number of authors on the effect of neurologic and neuromuscular problems on return to play. As they recover from COVID19 disease, athletes may experience tiredness, decreased neuromuscular function, and decreased muscle strength. Several additional COVIDrelated problems, such as general weariness, cognitive impairment, and coagulopathy, can occur in recovering athletes. (3)(4) The most common chronic cardiovascular dysautonomia in young and middle-aged people, primarily women, is postural orthostatic tachycardia syndrome (POTS). Chronic orthostatic intolerance, an abnormal increase in heart rate (HR) upon standing, and deconditioning are its defining characteristics. Post-viral autoimmune activation has been proposed as a potential cause of the condition (5) Interleukin-6 is crucial for athletes, particularly after arduous activity and after submerging in cold water. Immersion in cold water is linked to a little increase in IL-6 levels from post-exercise values. (6) Two studies described a syncopal episode in COVID-19 survivors 3 to 4 weeks after diagnosis, at the post-acute COVID-19 stage. This increases the likelihood that syncope had a role, not just during the illness’s acute stage but also as a long-term consequence. Patients in both of these cases underwent analysis for postural orthostatic tachycardia disorder, a part of the autonomic dysfunctions. As previously stated, unexplained pre/syncope accounted for 87.9% (531/604) of the detailed scenes and was the most frequent cause of the temporary loss of awareness. Reflex pre/syncope occurred 7.8% of the time overall (47/604). Orthostatic hypotension made up 2.2 percent (13/604) of the cases, and 2.2 percent (13/604) of the cases likely had cardiac pre/syncope. (7,8) Interleukin-6 (IL-6) is a localized energy sensor that is supplied to active skeletal muscle and can explain why there is an increase in plasma IL-6 during exercise. The length and intensity of the workout have an impact on the creation of IL-6, and moo muscle glycogen material supports this production. The discovery of abnormally elevated levels of IL-6 following arduous exercise has consistently been observed in several studies. After 6 minutes of vigorous exercise, a 2-fold increase in plasma IL-6 was seen. After 30 minutes of running by the treadmill, the blood level of IL-6 had significantly increased, reaching its peak after 2.5 hours. In other studies, when IL-6 levels weren’t monitored during the running workout but rather a few hours later, peak IL-6 levels were discovered right away after the workout, followed by a rapid decline. In this manner, maximal IL-6 levels (100-fold increment) were assessed immediately following the 3-3.5 h race. (9) Peak IL-6 levels are attained at the conclusion of the workout or soon after. Chronic IL-6 elevations cause hyperinsulinemia, lower body mass, and impaired insulin control of skeletal muscle glucose absorption. The level of circulating IL-6 is two to three times higher in senior patients with type 2 DM than it is in younger, healthy people. (10) As stated by NICE (National Institute for Health and Care Excellence), A significant proportion of acute COVID-19 survivors experience long-term physical and neuropsychiatric symptoms, which are categorized as “ongoing symptomatic COVID-19” (symptoms that continue for 4 to 12 weeks after the onset of the illness) and “post-COVID-19 syndrome” or “long COVID” (symptoms that continue for more than 12 weeks). We hypothesize that inflammatory c
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🖺 Full Text HTML: <a href="https://osf.io/4vn7e/" target="_blank">Can long-term post-COVID-19 fainting syndrome explain why a US artist swimmer Anita Alvarez has recurrent fainting attacks after diving during a swimming competition? Does interleukin-6 play a role?</a>
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<li><strong>Intensity of sample processing methods impacts wastewater SARS-CoV-2 whole genome amplicon sequencing outcomes</strong> -
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Wastewater SARS-CoV-2 surveillance has been deployed since the beginning of the COVID-19 pandemic to monitor dynamics in virus burden in local communities. Genomic surveillance of SARS-CoV-2 in wastewater, particularly the efforts for whole genome sequencing for variant tracking or identification, are comparatively challenging due to low target concentration, complex microbial and chemical background, and lack of robust nucleic acid recovery experimental procedures. The intrinsic sample limitations are inherent to wastewater. In this study, we evaluated impacts from sample types, certain sample intrinsic features, and processing and sequencing methods on sequencing outcomes with a specific focus on the breadth of genome coverage. We collected 184 composite and grab wastewater samples from the Chicago area between March to October 2021 for SARS-CoV-2 quantification and genomic surveillance. Samples were processed using a mixture of processing methods reflecting different homogenization intensities (HA+Zymo beads, HA+glass beads, and Nanotrap), and were sequenced using two sequencing library preparation kits (the Illumina COVIDseq kit and the QIAseq DIRECT kit). A synthetic SARS-CoV-2 RNA experiment was performed to validate the potential impacts of processing methods on sequencing outcomes. Our findings suggested that 1) SARS-CoV-2 whole genome sequencing outcomes were associated with sample types and processing methods 2) in less intensive method processed samples (HA+glass beads), higher genome breadth of coverage in sequencing (over 80%) was associated with N1 concentration > 105 cp/L, while in intensive method (HA+Zymo beads), qPCR results were inconsistent with sequencing outcomes, and 3) sample processing methods and sequencing kits, rather than the extraction methods or intrinsic features of wastewater samples, played important roles in wastewater SARS-CoV-2 amplicon sequencing. Overall, extra attention should be paid to wastewater sample processing (e.g., concentration and homogenization) for sufficient, good quality RNA yield for downstream sequencing.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280217v1" target="_blank">Intensity of sample processing methods impacts wastewater SARS-CoV-2 whole genome amplicon sequencing outcomes</a>
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<li><strong>Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance</strong> -
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Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups. Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention. Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests. Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280222v1" target="_blank">Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance</a>
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<li><strong>Higher risk of SARS-CoV-2 Omicron BA.4/5 infection than of BA.2 infection after previous BA.1 infection, the Netherlands, 2 May to 24 July 2022</strong> -
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We investigate differences in protection from previous infection and/or vaccination against infection with Omicron BA.4/5 or BA.2. We observed a higher percentage of registered previous SARS-CoV-2 infections among 19836 persons infected with Omicron BA.4/5 compared to 7052 persons infected with BA.2 (31.3% vs. 20.0%) between 2 May and 24 July 2022 (adjusted odds ratio (aOR) for testing week, age group and sex: 1.4 (95%CI: 1.3-1.5)). No difference was observed in the distribution of vaccination status between BA.2 and BA.4/5 cases (aOR: 1.1 for primary and booster vaccination). Among reinfections, those newly infected with BA4/5 had a shorter interval between infections and the previous infection was more often caused by BA.1, compared to those newly infected with BA.2 (aOR: 1.9 (1.5-2.6). This suggests immunity induced by BA.1 is less effective against a BA.4/5 infection than against a BA.2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.21.22280189v1" target="_blank">Higher risk of SARS-CoV-2 Omicron BA.4/5 infection than of BA.2 infection after previous BA.1 infection, the Netherlands, 2 May to 24 July 2022</a>
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<li><strong>Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue</strong> -
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Post-COVID-19 syndrome (PCS) summarizes persisting sequelae after infection with the severe-acute-respiratory-syndrome-Coronavirus-2 (SARS-CoV-2). PCS can affect patients of all covid-19 disease severities. As previous studies revealed impaired blood flow as a provoking factor for triggering PCS, it was the aim of the present study to investigate a potential association of self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT-Angiography (OCT-A) and quantified by the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic Fatigue (CF) was assessed with the variables Bell score, age and gender. The VD in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed considering the repetitions (12 times). Taking in account of such repetitions a mixed model was performed to detect possible differences in the least square means between different groups of analysis. An age effect on VD was observed between patients and controls (p<0.0001). Gender analysis yielded that women with PCS showed lower VD levels in SVP compared to male patients (p=0.0015). The PCS patients showed significantly lower VD of ICP as compared to the controls (p=0.0001, [CI: 0.32; 1]). Moreover, considering PCS patients, the mixed model reveals a significant difference between chronic fatigue (CF) and without CF in VD of SVP (p=0.0033, [CI: -4.5; -0.92]). The model included age, gender and the variable Bell score, representing a subjective marker for CF. Consequently, the retinal microcirculation might be an objective biomarker in subjective-reported chronic fatigue of patients with PCS.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.23.22280264v1" target="_blank">Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue</a>
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<li><strong>Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic</strong> -
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Background: Respiratory disease is a major cause of morbidity and mortality; however, current surveillance for circulating respiratory viruses is passive and biased. Seasonal circulation of respiratory viruses changed dramatically during the COVID-19 pandemic. More active methods for understanding respiratory disease dynamics are needed to better inform public health response and to guide clinical decision making. Wastewater-based epidemiology has been used to understand COVID-19, influenza A, and RSV infection rates at a community level, but has not been used to investigate other respiratory viruses. Methods: We measured concentrations of influenza A and B, RSV A and B, human parainfluenza (1-4), rhinovirus, seasonal human coronaviruses, and human metapneumovirus RNA in wastewater solids three times per week for 17 months spanning the COVID-19 pandemic at a wastewater treatment plant in California, USA. Novel probe-based assays were developed and validated for non-influenza viral targets. We compared viral concentrations to positivity rates for viral infections from clinical specimens submitted to sentinel laboratories. Findings: We detected RNA from all target viruses in wastewater solids. Human rhinovirus and seasonal coronaviruses were found at highest concentrations. Concentrations of viruses correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories. Measurements from wastewater indicated limited circulation of RSV A and influenza B, and human coronavirus OC43 dominated the seasonal human coronavirus infections while human parainfluenza 1 and 4A dominated among parainfluenza infections. Interpretation: Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 hours of sample collection, allowing real time information to inform public health response, clinical decision making, and individual behavior modifications.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280218v1" target="_blank">Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic</a>
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<li><strong>Commercial immunoglobulin products now contain neutralising antibodies against SARS-CoV-2 spike antibody which are detectable in patient serum</strong> -
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Antibody-deficient patients respond poorly to COVID-19 vaccination and are at risk of severe or prolonged infection. Prophylaxis with anti-SARS-CoV-2 monoclonal antibodies has been considered. We here demonstrate that many immunoglobulin preparations now contain neutralising anti-SARS-CoV-2 antibodies which are transmitted to patients in good concentrations, albeit with significant differences between products.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280216v1" target="_blank">Commercial immunoglobulin products now contain neutralising antibodies against SARS-CoV-2 spike antibody which are detectable in patient serum</a>
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<li><strong>Efficacy and safety of convalescent plasma versus standard care in hospitalized patients with COVID-19 from the Peruvian Social Security Health System: open-label, randomized, controlled clinical trial</strong> -
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OBJECTIVES: To assess the efficacy and safety of convalescent plasma plus standard of care (CP + SoC) compared with standard of care (SoC) alone in patients hospitalized for moderate to severe COVID-19 who do not yet require mechanical ventilation. METHODS: Phase 2 randomized, parallel-group, randomized, open-label, controlled, superiority, single-center clinical trial. This clinical trial has been registered in REPEC with the following ID: 013-20. Hospitalized adult patients with moderate to severe COVID-19 were enrolled. The allocation ratio was 1:1 in a variable-size permuted block randomization scheme. The primary outcome was death 28 days after the intervention. Secondary outcomes were mortality at 14 and 56 days, time to death at 56 days, time in the ICU at 28 days, time on a mechanical ventilator at 28 days, frequency of adverse events, and frequency of serious adverse events. RESULTS: A total of 64 participants were enrolled, 32 were assigned to CP + SoC, and 32 to SoC. One participant assigned to CP + SoC withdrew his informed consent before applying the treatment. At day 28, there were no statistically significant differences for the primary outcome between the CP + SoC and SoC groups (relative risk: 2.06; 95%CI 0.73 to 7.11; p = 0.190). No differences were found in the incidences of mortality at 56 days (hazard ratio: 2.21; 95%CI 0.66 to 7.33; p = 0.182), admission to the ICU at 28 days (sub-hazard ratio: 2.06; 95%CI 0.57 to 8.55; p = 0.250), admission to mechanical ventilation at 28 days (sub-hazard ratio: 2.19; 95%CI 0.57 to 8.51; p = 0.260). Estimates for days 14 were similar. No infusion-related adverse events were reported during the study. There were no statistically significant differences in the frequency of any adverse events (odds ratio: 2.74; 95%CI 0.90 to 9.10; p = 0.085) or the frequency of serious adverse events (odds ratio: 3.60; 95%CI 0.75 to 26.1; p = 0.75). CONCLUSIONS: No evidence was found that CP had a significant effect in reducing 28-day mortality. There was also no evidence that the frequency of adverse events was higher in those who received CP + SoC than those who received only SoC.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.21.22280195v1" target="_blank">Efficacy and safety of convalescent plasma versus standard care in hospitalized patients with COVID-19 from the Peruvian Social Security Health System: open-label, randomized, controlled clinical trial</a>
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<li><strong>Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19</strong> -
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Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care. Methods: We conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality. Results: A total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99-1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05-1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39-0.90). No differences in risk of serious adverse events including secondary infections. Conclusions: Infliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28-day mortality compared with standard of care. Trial registration: ClinicalTrials.gov (NCT04593940).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280245v1" target="_blank">Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19</a>
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<li><strong>Excess death estimates from multiverse analysis in 2009-2021</strong> -
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Excess death estimates have great value in public health, but they can be sensitive to analytical choices. Here we propose a multiverse analysis approach that considers all possible different time periods for defining the reference baseline and a range of 1 to 4 years for the projected time period for which excess deaths are calculated. We used data from the Human Mortality Database on 33 countries with detailed age-stratified death information on an annual basis during the period 2009-2021. The use of different time periods for reference baseline led to large variability in the absolute magnitude of the exact excess death estimates. However, the relative ranking of different countries compared to others for specific years remained largely unaltered. Averaging across all possible analyses, distinct time patterns were discerned across different countries. Countries had declines between 2009 and 2019, but the steepness of the decline varied markedly. There were also large differences across countries on whether the COVID-19 pandemic years 2020-2021 resulted in an increase of excess deaths and by how much. Consideration of longer projected time windows resulted in substantial shrinking of the excess deaths in many, but not all countries. Multiverse analysis of excess deaths over long periods of interest can offer a more unbiased approach to understand comparative mortality trends across different countries, the range of uncertainty around estimates, and the nature of observed mortality peaks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.21.22280219v1" target="_blank">Excess death estimates from multiverse analysis in 2009-2021</a>
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<li><strong>Fully Quantitative Measurements of Differential Antibody Binding to Spike Proteins from Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1 variants of SARS-CoV-2: Antibody Immunity Endotypes</strong> -
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A fully quantitative comparative analysis of the differential binding to spike variant proteins to SARS-CoV-2 has been performed for the variants: Wuhan (ancestral strain), Alpha, Beta, Gamma, Delta and Omicron BA.1. Evolution of immunity through five patient cohorts was studied including pre-pandemic, first infection, first vaccine, second vaccine and triple-vaccinated cohorts. A series of immunity endotypes has been observed: U(+) showing protection to all variants; single, double, triple, quadruple and quintuple dropout endotypes U(+/-;); some with no variant protection other than Wuhan vaccine spike U(-); and some unclassified, U(~). These endotypes may be imprinted. In the triple-vaccinated cohort (n = 54) there is a U(+) incidence of 65% (95% CI 51% - 76%) suggesting between half and three-quarters of the population have universal variant vaccine antibody protection; U(-) 6% (95% CI 2% - 15%) of the population have no variant antibody protection provided by the vaccine; and U(+/-;)) with at least one dropout has a incidence of 20% (95% CI 12% - 33%). Extending the cohort incidence to the population, up to 76% of the population may have an imprinted immunity endotype to an epitope that is effective against all variants; critical for both protection and binding to the ACE2 receptor: a universal immunity endotype. However, up to 33% of the population may have an immunity endotype that will never produce an effective antibody response to SARS-CoV-2 unless the immunity imprint is broken.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.23.22280271v1" target="_blank">Fully Quantitative Measurements of Differential Antibody Binding to Spike Proteins from Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1 variants of SARS-CoV-2: Antibody Immunity Endotypes</a>
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<li><strong>Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis</strong> -
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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses a risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including selection of adaptive mutations and emergence of new variant lineages. Here we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate transmission of SARS-CoV-2 between human and non-human species and to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with negligible transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs, potentially due to small sample sizes. However, we identified three SNVs statistically associated with mink and 26 with deer. Of these SNVs, ~[2/3] were plausibly introduced into these animal species from local human populations, while the remaining ~[1/3] were more likely derived in animal populations and are thus top candidates for experimental studies of species-specific adaptation. Together, our results highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.02.494559v2" target="_blank">Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis</a>
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</div></li>
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<li><strong>Pharmacological inhibition of bromodomain and extra-terminal proteins induces NRF-2-mediated inhibition of SARS-CoV-2 replication and is subject to viral antagonism</strong> -
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Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential therapeutics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-induced antiviral activity and its susceptibility to viral antagonism remain incompletely understood. iBET treatment transiently inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. Our functional assays confirmed JQ-1-mediated downregulation of ACE2 expression and multi-omics analysis uncovered induction of an antiviral NRF-2-mediated cytoprotective response as an additional antiviral component of JQ-1 treatment. Serial passaging of SARS-CoV-2 in the presence of JQ-1 resulted in predominance of ORF6-deficient variants. JQ-1 antiviral activity was transient in human bronchial airway epithelial cells (hBAECs) treated prior to infection and absent when administered therapeutically. We propose that JQ-1 exerts pleiotropic effects that collectively induce a transient antiviral state that is ultimately nullified by an established SARS-CoV-2 infection, raising questions on their clinical suitability in the context of COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.22.508962v1" target="_blank">Pharmacological inhibition of bromodomain and extra-terminal proteins induces NRF-2-mediated inhibition of SARS-CoV-2 replication and is subject to viral antagonism</a>
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</div></li>
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<li><strong>Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection</strong> -
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Defective viral genomes (DVGs) have been identified in many RNA viruses as a major factor influencing antiviral immune response and viral pathogenesis. However, the generation and function of DVGs in SARS-CoV-2 infection are less known. In this study, we elucidated DVG generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from RNA-seq datasets of in vitro infections and autopsy lung tissues of COVID-19 patients. Four genomic hotspots were identified for DVG recombination and RNA secondary structures were suggested to mediate DVG formation. Functionally, bulk and single cell RNA-seq analysis indicated the IFN stimulation of SARS-CoV-2 DVGs. We further applied our criteria to the NGS dataset from a published cohort study and observed significantly higher DVG amount and frequency in symptomatic patients than that in asymptomatic patients. Finally, we observed unusually high DVG frequency in one immunosuppressive patient up to 140 days after admitted to hospital due to COVID-19, first-time suggesting an association between DVGs and persistent viral infections in SARS-CoV-2. Together, our findings strongly suggest a critical role of DVGs in modulating host IFN responses and symptom development, calling for further inquiry into the mechanisms of DVG generation and how DVGs modulate host responses and infection outcome during SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.22.509123v1" target="_blank">Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Olfactory training with essential oils; Other: Olfactory training with fragrance-free oils<br/><b>Sponsor</b>: Ditte Gertz Mogensen<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Efficacy and Safety of TADIOS as an Adjuvant Therapy in Patients Diagnosed With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: TADIOS; Drug: Placebo<br/><b>Sponsor</b>: Helixmith Co., Ltd.<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Fourth Dose Study in Australia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Tozinameran; Biological: Elasomeran; Biological: Bivalent Pfizer-BioNTech; Biological: Bivalent Moderna<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg; Biological: BNT162b4 5 µg; Biological: BNT162b4 10 µg; Biological: BNT162b4 15 µg<br/><b>Sponsors</b>: BioNTech SE; Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trial of 2nd Booster Dose of COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Invitation to get a 2nd booster dose of COVID-19 vaccine<br/><b>Sponsor</b>: Norwegian Institute of Public Health<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PBI-0451; Drug: Placebo<br/><b>Sponsor</b>: Pardes Biosciences, Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AD17002 + Formulation buffer; Biological: Placebo<br/><b>Sponsors</b>: Advagene Biopharma Co. Ltd.; Gadjah Mada University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Community-based Health Education based on core intervention package; Behavioral: Health Information Sharing Group<br/><b>Sponsors</b>: The Hong Kong Polytechnic University; Food and Health Bureau, Hong Kong<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia</strong> - <b>Conditions</b>: Olfactory Disorder; COVID-19<br/><b>Intervention</b>: Drug: Simvastatin<br/><b>Sponsors</b>: Washington University School of Medicine; Duke University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cardiopulmonary Rehabilitation in Post-acute COVID-19 Syndrome</strong> - <b>Condition</b>: Post Acute COVID-19 Syndrome<br/><b>Interventions</b>: Other: Cardiopulmonary rehabilitation; Other: Health education<br/><b>Sponsor</b>: Taipei Medical University Shuang Ho Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Active Intervention Group<br/><b>Sponsor</b>: Pennington Biomedical Research Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the Efficacy of Mouth Rinses With Commercial Mouthwashes to Decrease Viral Load in Saliva in COVID-19 Patients</strong> - <b>Condition</b>: covid19<br/><b>Interventions</b>: Drug: Lacer Clorhexidina Colutorio; Drug: Lacer Clorhexidine 0.20% Colutorio; Drug: Gingilacer Encías Delicadas Colutorio; Drug: Distilled water<br/><b>Sponsors</b>: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana; Hospital Universitario Fundación Jiménez Díaz; Hospital Universitario Infanta Elena<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of COVID-19 Positive Patients</strong> - <b>Conditions</b>: Covid19; Hydrogen-oxygen Gas; AMS-H-03<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen)<br/><b>Sponsor</b>: Ruijin Hospital<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of COVID-19 Vaccine in Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: low-dose LYB001; Biological: Recombinant COVID-19 Vaccine (CHO Cell); Biological: high-dose LYB001<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID-19 Syndrome in Primary Care: A Novel Protocol of Exercise Intervention “CON-VIDA Clinical Trial”</strong> - <b>Conditions</b>: COVID-19; Long COVID; Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: EXERCISE<br/><b>Sponsor</b>: Universidad San Jorge<br/><b>Active, not recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope</strong> - Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pediatric Residency Training amid the COVID-19 Pandemic: Exploring the Impact of Supervision and Clinical Practice Guidelines on Clinical and Financial Outcomes</strong> - CONCLUSION: Direct supervision inhibited the negative impact of the COVID-19 pandemic on both clinical and financial outcomes of non-COVID-19 inpatient care by pediatric residents, while CPG only inhibited the negative impact on financial outcomes. Implication of This Study. In a disaster, the availability of CPG and direct supervision makes AMC hospitals able to inhibit the negative impact of disasters on clinical and financial outcomes.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Jian-Ti-Kang-Yi decoction alleviates poly(I:C)-induced pneumonia by inhibiting inflammatory response, reducing oxidative stress, and modulating host metabolism</strong> - Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structural Basis for the Inhibition of Coronaviral Main Proteases by a Benzothiazole-Based Inhibitor</strong> - The ongoing spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused hundreds of millions of cases and millions of victims worldwide with serious consequences to global health and economies. Although many vaccines protecting against SARS-CoV-2 are currently available, constantly emerging new variants necessitate the development of alternative strategies for prevention and treatment of COVID-19. Inhibitors that target the main protease (M^(pro)) of SARS-CoV-2, an…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chemically Modified Bovine β-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks</strong> - Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine β-lactoglobulin (3HP-β-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Bovine Seminal Plasma Protein PDC-109 Possesses Pan-Antiviral Activity</strong> - Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines, and growth factors, with various functions during insemination and fertilization. The seminal plasma protein PDC-109 is one of the major soluble components of the bovine ejaculate and is crucially important for sperm motility, capacitation, and acrosome reaction. A hitherto underappreciated function of seminal plasma is its anti-microbial and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 RBD-Specific Antibodies Induced Early in the Pandemic by Natural Infection and Vaccination Display Cross-Variant Binding and Inhibition</strong> - The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Broad-Spectrum Small-Molecule Inhibitors of the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction from a Chemical Space of Privileged Protein Binders</strong> - Therapeutically useful small-molecule inhibitors (SMIs) of protein-protein interactions (PPIs) initiating the cell attachment and entry of viruses could provide novel alternative antivirals that act via mechanisms similar to that of neutralizing antibodies but retain the advantages of small-molecule drugs such as oral bioavailability and low likelihood of immunogenicity. From screening our library, which is focused around the chemical space of organic dyes to provide good protein binders, we…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bacteriophage-Derived Double-Stranded RNA Exerts Anti-SARS-CoV-2 Activity In Vitro and in Golden Syrian Hamsters In Vivo</strong> - Bacteriophage-derived dsRNA, known as Larifan, is a nationally well-known broad-spectrum antiviral medication. This study aimed to ascertain the antiviral activity of Larifan against the novel SARS-CoV-2 virus. Larifan’s effect against SARS-CoV-2 in vitro was measured in human lung adenocarcinoma (Calu3) and primary human small airway epithelial cells (HSAEC), and in vivo in the SARS-CoV-2 infection model in golden Syrian hamsters. Larifan inhibited SARS-CoV-2 replication both in vitro and in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Quercetin in the Prevention and Treatment of Coronavirus Infections: A Focus on SARS-CoV-2</strong> - The COVID-19 outbreak seems to be the most dangerous challenge of the third millennium due to its highly contagious nature. Amongst natural molecules for COVID-19 treatment, the flavonoid molecule quercetin (QR) is currently considered one of the most promising. QR is an active agent against SARS and MERS due to its antimicrobial, antiviral, anti-inflammatory, antioxidant, and some other beneficial effects. QR may hold therapeutic potential against SARS-CoV-2 due to its inhibitory effects on…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plant Metabolites as SARS-CoV-2 Inhibitors Candidates: In Silico and In Vitro Studies</strong> - Since it acquired pandemic status, SARS-CoV-2 has been causing all kinds of damage all over the world. More than 6.3 million people have died, and many cases of sequelae are in survivors. Currently, the only products available to most of the world’s population to fight the pandemic are vaccines, which still need improvement since the number of new cases, admissions into intensive care units, and deaths are again reaching worrying rates, which makes it essential to compounds that can be used…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity</strong> - The replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its main protease (M^(pro)), which is a plausible therapeutic target for coronavirus disease 2019 (COVID-19). Although numerous in silico studies reported the potential inhibitory effects of natural products including cannabis and cannabinoids on SARS-CoV-2 M^(pro), their anti-M^(pro) activities are not well validated by biological experimental data. Herein, a library of minor cannabinoids…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Epigallocatechin Gallate Stabilized by Cyclodextrin Inactivates Influenza Virus and Human Coronavirus 229E</strong> - Natural products are attractive antiviral agents because they are environment-friendly and mostly harmless. Epigallocatechin gallate (EGCg), a type of catechin, is a well-known natural antiviral agent that can inhibit various viruses. However, EGCg easily oxidizes and loses its physiological activity. Although this problem can be overcome by combining EGCg with cyclodextrin (CD-EGCg), which makes it stable in water at high concentrations, the antiviral effect of this compound remains unclear….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants</strong> - SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Bases of Serotonin Reuptake Inhibitor Antidepressant-Attributed Effects in COVID-19: A New Insight on the Role of Bradykinins</strong> - Widely available effective drugs to treat coronavirus disease-2019 (COVID-19) are still limited. Various studies suggested the potential contribution of selective serotonin-reuptake inhibitor (SSRI) antidepressants to alleviate the clinical course of COVID-19. Initially, SSRI antidepressant-attributed anti-COVID-19 activity was attributed to their direct agonistic or indirect serotonin-mediated stimulation of sigma-1 receptors (Sig1-R). Thereafter, attention was drawn to the property of SSRI…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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