188 lines
55 KiB
HTML
188 lines
55 KiB
HTML
<!DOCTYPE html>
|
||
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
|
||
<meta charset="utf-8"/>
|
||
<meta content="pandoc" name="generator"/>
|
||
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
|
||
<title>03 March, 2023</title>
|
||
<style>
|
||
code{white-space: pre-wrap;}
|
||
span.smallcaps{font-variant: small-caps;}
|
||
span.underline{text-decoration: underline;}
|
||
div.column{display: inline-block; vertical-align: top; width: 50%;}
|
||
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
|
||
ul.task-list{list-style: none;}
|
||
</style>
|
||
<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>
|
||
<body>
|
||
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
|
||
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
|
||
<ul>
|
||
<li><a href="#from-preprints">From Preprints</a></li>
|
||
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
|
||
<li><a href="#from-pubmed">From PubMed</a></li>
|
||
<li><a href="#from-patent-search">From Patent Search</a></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
|
||
<ul>
|
||
<li><strong>Warning “Don’t spread” vs. “Don’t be a spreader” to prevent the COVID-19 pandemic</strong> -
|
||
<div>
|
||
The coronavirus disease 2019 (COVID-19) outbreak is threatening not only health but also life worldwide. It is important to encourage citizens to voluntarily practise infection prevention (IP) behaviours such as social distancing and self-restraint. Previous research on social cognition suggested that emphasising self-identity is key to changing a person’s behaviour. The present study investigated whether reminders that highlight self-identity would be effective in changing intention and behaviour related to the COVID-19 outbreak, and hypothesised that those who read reminders highlighting self-identity (‘Don’t be a spreader’) would change IP intention and behaviour better than those who read ‘Don’t spread’ or no reminder. We conducted a two-wave survey of the same participants with a one-week interval, during which we assigned one of three reminder conditions to the participants: ‘Don’t spread’ (spreading condition), ‘Don’t be a spreader’ (spreader condition), and no reminder (control condition). Participants marked their responses to IP intentions and actual behaviours each week based on the Japanese Ministry of Health, Labour, and Welfare guidelines. While the results did not show significant differences between the conditions, the post-hoc analyses showed significant equivalence in either IP intentions or behavioural scores. We discussed the results from the perspective of the effect size, ceiling effects, and ways of manipulation checks as future methods with more effective persuasive messaging. Following in-principle acceptance, the approved Stage 1 version of this manuscript was preregistered on the OSF at https://doi.org/10.17605/OSF.IO/KZ5Y4. This preregistration was performed prior to data collection and analysis.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://psyarxiv.com/u4z3e/" target="_blank">Warning “Don’t spread” vs. “Don’t be a spreader” to prevent the COVID-19 pandemic</a>
|
||
</div></li>
|
||
<li><strong>Distancing from a stigmatized identity: Explaining hostility by marginalized racial groups toward new immigrants</strong> -
|
||
<div>
|
||
Discrimination is often perceived as stemming from outgroups. The UN Sustainable Development Goal 10 focused on reducing inequalities calls attention also to intragroup hostilities. In the US, intragroup hostilities between Latinos/as might occur if disassociation from a stigmatized sub-group protects one’s status. This chapter tests potential disassociation effects by examining whether US Latinos/as distance themselves from an associated stigmatized identity by supporting adverse policies regarding Latino/a immigrants. Two studies (n=273 and n=8634) found that citizenship status was linked to support for adverse policies: more US-born Latinos/as considered immigrants a burden than Latinos/as of unknown status or non-citizens. Some Latino/a citizens might cut off reflected failure associated with being an immigrant because distancing might support coping with cultural demands of US residence and distancing from recent immigrants might prevent transference of negative stereotypes. As inequalities increase overall in the post-COVID-19 era, intragroup bias may worsen outcomes for stigmatized sub-groups.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://psyarxiv.com/za8u9/" target="_blank">Distancing from a stigmatized identity: Explaining hostility by marginalized racial groups toward new immigrants</a>
|
||
</div></li>
|
||
<li><strong>Systematic analyses of the resistance potential of drugs targeting SARS-CoV-2 main protease</strong> -
|
||
<div>
|
||
Drugs that target the main protease (Mpro) of SARS-CoV-2 are effective therapeutics that have entered clinical use. Wide-scale use of these drugs will apply selection pressure for the evolution of resistance mutations. To understand resistance potential in Mpro, we performed comprehensive surveys of amino acid changes that can cause resistance in a yeast screen to nirmatrelvir (contained in the drug Paxlovid), and ensitrelvir (Xocova) that is currently in phase III trials. The most impactful resistance mutation (E166V) recently reported in multiple viral passaging studies with nirmatrelvir showed the strongest drug resistance score for nirmatrelvir, while P168R had the strongest resistance score for ensitrelvir. Using a systematic approach to assess potential drug resistance, we identified 142 resistance mutations for nirmatrelvir and 177 for ensitrelvir. Among these mutations, 99 caused apparent resistance to both inhibitors, suggesting a strong likelihood for the evolution of cross-resistance. Many mutations that exhibited inhibitor-specific resistance were consistent with distinct ways that each inhibitor protrudes beyond the substrate envelope. In addition, mutations with strong drug resistance scores tended to have reduced function. Our results indicate that strong pressure from nirmatrelvir or ensitrelvir will select for multiple distinct resistant lineages that will include both primary resistance mutations that weaken interactions with drug while decreasing enzyme function and secondary mutations that increase enzyme activity. The comprehensive identification of resistance mutations enables the design of inhibitors with reduced potential of developing resistance and aids in the surveillance of drug resistance in circulating viral populations.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.02.530652v1" target="_blank">Systematic analyses of the resistance potential of drugs targeting SARS-CoV-2 main protease</a>
|
||
</div></li>
|
||
<li><strong>Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping</strong> -
|
||
<div>
|
||
The emergence of new variants of the SARS-CoV-2 virus has posed a significant challenge in developing broadly neutralizing antibodies (nAbs) with guaranteed therapeutic potential. Some nAbs, such as Sotrovimab, have exhibited varying levels of efficacy against different variants, while others, such as Bebtelovimab and Bamlanivimab-etesevimab are ineffective against specific variants, including BQ.1.1 and XBB. This highlights the urgent need for developing broadly active mAbs providing prophylactic and therapeutic benefits to high-risk patients, especially in the face of the risk of reinfection from new variants. Here, we aimed to investigate the feasibility of redirecting existing mAbs against new variants of SARS-CoV-2, as well as to understand how BQ.1.1 and XBB.1.5 can evade broadly neutralizing mAbs. By mapping epitopes and escape sites, we discovered that the new variants evade multiple mAbs, including FDA-approved Bebtelovimab, which showed resilience against other Omicron variants. Our approach, which included simulations, free energy perturbations, and shape complementarity analysis, revealed the possibility of identifying mAbs that are effective against both BQ.1.1 and XBB.1.5. We identified two broad-spectrum mAbs, R200-1F9 and R207-2F11, as potential candidates with increased binding affinity to XBB.1.5 and BQ.1.1 compared to the wild-type virus. Additionally, we propose that these mAbs do not interfere with ACE2 and bind to conserved epitopes on the RBD that are not-overlapping, potentially providing a solution to neutralize these new variants either independently or as part of a combination (cocktail) treatment.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.01.530717v1" target="_blank">Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping</a>
|
||
</div></li>
|
||
<li><strong>Isolation of ACE2-dependent and -independent sarbecoviruses from Chinese horseshoe bats</strong> -
|
||
<div>
|
||
While the spike proteins from SARS-CoV and SARS-CoV-2 bind to host ACE2 to infect cells, the majority of bat sarbecoviruses cannot use ACE2 from any species. Despite their discovery almost 20 years ago, ACE2-independent sarbecoviruses have never been isolated from field samples, leading to the assumption these viruses pose little risk to humans. We have previously shown how spike proteins from a small group of ACE2-independent bat sarbecoviruses may possess the ability to infect human cells in the presence of exogenous trypsin. Here, we adapted our earlier findings into a virus isolation protocol, and recovered two new ACE2-dependent viruses, RsYN2012 and RsYN2016, as well as an ACE2-independent virus, RsHuB2019. Although our stocks of RsHuB2019 rapidly acquired a tissue-culture adaption that rendered the spike protein resistant to trypsin, trypsin was still required for viral entry, suggesting limitations on the exogenous entry factors that support bat sarbecoviruses. Electron microscopy revealed ACE2-independent sarbecoviruses have a prominent spike corona and share similar morphology to other coronaviruses. Our findings demonstrate a broader zoonotic threat posed by sarbecoviruses and shed light onto the intricacies of coronavirus isolation and propagation in vitro.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.02.530738v1" target="_blank">Isolation of ACE2-dependent and -independent sarbecoviruses from Chinese horseshoe bats</a>
|
||
</div></li>
|
||
<li><strong>The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
COVID-19 has challenged the scientific community in the search for biological markers and information that can contribute to the early management of the severe disease. Given the global scale of COVID-19, including reports of reinfection even in the presence of effective vaccines, we have not yet been able to eradicate the disease. This factor implies the emergence of new waves and an increasing number of hospitalizations. This study aimed to characterize the neutralizing antibody (Nab) geometric mean titers (GMTs) in hospitalized patients with COVID-19 and to evaluate the association with length of stay, comorbidities, and patient outcome. Among the 103 participants, 84 (81.5%) had some previous condition associated with worsening health, and 31 (30%) died. We found that neutralization potency varied greatly across individuals and was significantly higher in patients discharged before 14 days than in patients who stayed longer in the hospital. During the study period, 15 people living with HIV (PLWH) were hospitalized, and no significant difference in clinical characteristics or anti-SARS-CoV-2 Nabs was observed. However, PLWH with severe COVID-19 were younger (41.7, IQR=17.5) than other hospitalized COVID-19 patients (59.3, IQR=22, P <0.01). A high anti-HIV-1 antibody GMT of 583.9 (95% CI: 344-990) was detected, demonstrating maintenance of anti-HIV-1 Nab production among PLWH coinfected with SARS-CoV-2. Therefore, these results indicate that neutralizing antibodies are not the only immunological response capable of controlling disease progression. Nevertheless, these data highlight the importance of more Nab screening studies to predict shorter hospital stays.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.02.23286693v1" target="_blank">The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients</a>
|
||
</div></li>
|
||
<li><strong>Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Background: Spironolactone has been proposed as a potential modulator of SARS-CoV-2 cellular entry. We aimed to measure the effect of spironolactone use on the risk of adverse outcomes following COVID-19 hospitalization. Methods: We performed a retrospective cohort study of COVID-19 outcomes for patients with or without exposure to spironolactone, using population-scale claims data from the Komodo Healthcare Map. We identified all patients with a hospital admission for COVID-19 in the study window, defining treatment status based on spironolactone prescription orders. The primary outcomes were progression to respiratory ventilation or mortality during the hospitalization. Odds ratios (OR) were estimated following either 1:1 propensity score matching (PSM) or multivariable regression. Subgroup analysis was performed based on age, gender, body mass index (BMI), and dominant SARS-CoV-2 variant. Findings: Among 898,303 eligible patients with a COVID-19-related hospitalization, 16,324 patients (1.8%) had a spironolactone prescription prior to hospitalization. 59,937 patients (6.7%) met the ventilation endpoint, and 26,515 patients (3.0%) met the mortality endpoint. Spironolactone use was associated with a significant reduction in odds of both ventilation (OR 0.82; 95% CI: 0.75-0.88; p < 0.001) and mortality (OR 0.88; 95% CI: 0.78-0.99; p = 0.033) in the PSM analysis, supported by the regression analysis. Spironolactone use was associated with significantly reduced odds of ventilation for all age groups, men, women, and non-obese patients, with the greatest protective effects in younger patients, men, and non-obese patients. Interpretation: Spironolactone use was associated with a protective effect against ventilation and mortality following COVID-19 infection, amounting to up to 64% of the protective effect of vaccination against ventilation and consistent with an androgen-dependent mechanism. The findings warrant initiation of large-scale randomized controlled trials to establish a potential therapeutic role for spironolactone in COVID-19 patients.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.28.23286515v1" target="_blank">Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study</a>
|
||
</div></li>
|
||
<li><strong>Use of a digital application to enhance communication and triage between care homes and National Health Service community services in the United Kingdom: a qualitative evaluation</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Recent years have seen a rise in digital interventions to improve coordination between care homes and NHS services, supporting remote sharing of data on the health of care home residents. Such interventions were key components in the response to the COVID-19 pandemic. This paper presents findings from the qualitative component of an evaluation of an implementation of the HealthCall Digital Care Homes application, across sites in northern England. The implementation commenced prior to the pandemic and continued throughout. Semi-structured, qualitative interviews were held with stakeholders. Interviews were conducted remotely (October 2020 -June 2021). Data were analysed via a reflexive thematic analysis then mapped against Normalization Process Theory (NPT) constructs (coherence, collective action, cognitive participation, and reflexive monitoring) providing a framework to assess implementation success. Thirty-five participants were recruited: 16 care home staff, six NHS community nurses, five relatives of care home residents, four HealthCall team members, three care home residents, and one local authority commissioner. Despite facing challenges such as apprehension towards digital technology among care home staff, the application was viewed positively across stakeholder groups. The HealthCall team maintained formal and informal feedback loop with stakeholders. This resulted in revisions to the intervention and implementation. Appropriate training and problem solving from the HealthCall team and buy-in from care home and NHS staff were key to achieving success across NPT constructs. While this implementation appears broadly successful, establishing rapport and maintaining on-going support requires significant time, financial backing, and the right individuals in place across stakeholder groups to drive implementation and intervention evolution. The digital literacy of care home staff requires encouragement to enhance their readiness for digital interventions. The COVID-19 pandemic has pushed this agenda forward. Problems with stability across the workforce within care homes need to be addressed to avoid skill loss and support embeddedness of digital interventions.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.02.23286669v1" target="_blank">Use of a digital application to enhance communication and triage between care homes and National Health Service community services in the United Kingdom: a qualitative evaluation</a>
|
||
</div></li>
|
||
<li><strong>Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment.</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
The mutation rate of the Omicron sublineage has led to baseline resistance against all previously authorized anti-Spike monoclonal antibodies (mAbs). Nevertheless, in case more antiviral mAbs will be authorized in the future, it is relevant to understand how frequently treatment-emergent resistance has emerged so far, under different combinations and in different patient subgroups. We report the results of a systematic review of the medical literature for case reports and case series for treatment-emergent immune escape, which is defined as emergence of a resistance-driving mutation in at least 20% of sequences in a given host at a given timepoint. We identified 31 publications detailing 201 cases that included different variants of concern (VOC) and found that the incidence of treatment emergent-resistance ranged from 10% to 50%. Most of the treatment-emergent resistance events occurred in immunocompromised patients. Interestingly, resistance also emerged against cocktails of two mAbs, albeit at lower frequencies. The heterogenous therapeutic management of those cases doesn9t allow inferences about the clinical outcome in patients with treatment-emergent resistance. Furthermore, we noted a temporal correlation between the introduction of mAb therapies and a subsequent increase in SARS-CoV-2 sequences across the globe carrying mutations conferring resistance to that mAb, raising concern as to whether these had originated in mAb-treated individuals. Our findings confirm that treatment-emergent immune escape to anti-Spike mAbs represents a frequent and concerning phenomenon and suggests that these are associated with mAb use in immunosuppressed hosts.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.02.23286677v1" target="_blank">Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment.</a>
|
||
</div></li>
|
||
<li><strong>On the changing role of individuals in different age groups in propagating the Omicron epidemic waves in France</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Objectives: In late December 2022, rates of mortality in France (over 2,500 daily deaths) have reached levels not seen since April 2020, with the most pronounced increase in mortality recorded in nursing homes. Epidemics of Omicron and influenza have both contributed to those high mortality levels in late 2022. The roles of different age groups in propagating Omicron epidemics in the whole community require a better characterization, particularly given that in France, vaccination coverage for the 2nd booster for COVID-19 is limited and largely restricted to persons aged over 60y. Patients and Methods: We examined the role of individuals in different age groups in propagating different waves of Omicron epidemics in France between March 1 through Dec. 30, 2022 using previously developed methodology based on the relative risk (RR) statistic that measures the change in the proportion of each age group among all cases before vs. after the peak of an epidemic wave. Higher value of the RR statistic for a given age group suggests a disproportionate depletion of susceptible individuals in that age group during the ascent of the epidemic (due to increased contact rates and/or susceptibility to infection). Results: For the Spring wave (March 14 through May 15), the highest RR estimate belonged to children aged 10-19y (RR=1.92 (95% CI (1.18,3.12)), followed by adults aged 40-49y (RR=1.45 (1.09,1.93)) and children aged 0-9y (RR=1.31 (0.98,1.74)). For the Summer wave (June 27 through Aug. 21), the highest RR estimate belong to children aged 0-9y (RR=1.61 (1.13,2.30)) followed by children aged 10-19y (RR=1.59 (0.77,3.26)) and adults aged 20-29y (RR=1.42 (0.91,2.23)). For the Autumn wave (Sep. 18 through Nov. 12), the highest RR estimate belonged to children aged 10-19y (RR=1.65 (0.72,3.75)), followed by adults aged 30-39y (RR=1.39 (0.83,2.33)) and 20-29y (RR=1.21 (0.66,2.23)). For the Autumn-Winter Wave (Nov. 23 through Dec. 30), the highest RR estimate belonged to persons aged 30-39y (RR=1.43 (0.79,2.57)), followed by persons aged 80-89y (RR= 1.17 (0.99,1.4)) and persons aged 40-49y (RR= 1.15 (0.73,1.82))). Conclusions: Increasing booster vaccination coverage for all adults, as possibly for children should help mitigate future Omicron epidemics. The estimate for the RR statistic in persons aged 80-89y for the Autumn-Winter Omicron wave suggests that additional efforts should be considered for preventing the spread of Omicron infection in elderly persons, including in Long-Term Care facilities.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.22.22283867v3" target="_blank">On the changing role of individuals in different age groups in propagating the Omicron epidemic waves in France</a>
|
||
</div></li>
|
||
<li><strong>Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine - either heterologous (PHH-1V group) or homologous (BNT162b2 group) - in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001), 1.31 (p=0.0007) and 0.86 (p=0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p<0.0001), 0.65 (p<0.0001) and 0.56 (p=0.003) for the Beta variant; 1.01 (p=0.92), 0.88 (p=0.11) and 0.52 (p=0.0003) for the Delta variant; and 0.59 (p=<0.0001), 0.66 (p<0.0001) and 0.57 (p=0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277210v5" target="_blank">Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</a>
|
||
</div></li>
|
||
<li><strong>Open Science Discovery of Potent Non-Covalent SARS-CoV-2 Main Protease Inhibitors</strong> -
|
||
<div>
|
||
The COVID-19 pandemic was a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Pandemics could be prevented in principle by accessible, easily deployable broad-spectrum oral antivirals. Here we report the results of the COVID Moonshot, a fully open-science, crowd sourced, structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical series that is differentiated from current Mpro inhibitors in that it maintains a new non-covalent, non-peptidic scaffold with nanomolar potency. Our approach leveraged crowdsourcing, high-throughput structural biology, machine learning, and exascale molecular simulations and high-throughput chemistry. In the process, we generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (>18,000 designs), crystallographic data (>840 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.10.29.339317v4" target="_blank">Open Science Discovery of Potent Non-Covalent SARS-CoV-2 Main Protease Inhibitors</a>
|
||
</div></li>
|
||
<li><strong>Easing pandemic-related restrictions, easing psychosocial stress factors in families with infants and toddlers? Cross-sectional results of the three wave CoronabaBY study from Germany.</strong> -
|
||
<div>
|
||
Background: Families with young children are particularly vulnerable for the stressors induced by the COVID-19 pandemic. However, studies on their psychosocial situation during the course of the crisis are still sparse. Methods: In a comparison of three survey waves (wave I and III = high incidences), we cross-sectionally investigated the proportion of families (Ntotal = 2,940) with children aged 0-3 years experiencing pandemic burden, parenting stress, and parental and child mental health problems in relation to COVID-19 incidences and restrictions in Southern Germany. Potential influencing factors were also explored. Results: The number of parents with a high pandemic burden decreased from 65.3% to 57.3% in wave II and rose to 62.2% in wave III (significant changes except wave II vs. III). Participants with high parenting stress increased from 38.2% to 46.1% and 51.2% (all significant changes). The number of mothers with affective symptoms remained constant with a maximum of 28.3%. The proportion of affected fathers decreased from 25.4% in wave I to 14.3% in wave II and rose significantly to 28.4% in wave III. Infants with crying sleeping problems increased significantly from 26.4% in wave I to 35.5% in wave III. Toddlers’ emotional and behavioral problems showed a similar trend with 23.9% being affected in wave III (no significant changes after adjusting for child age and gender). Increased family conflicts during the pandemic were the strongest predictor for parenting stress (ß = .355), maternal (ß= .305), infants’ (ß= .149) and toddlers’ (ß= .216) mental health problems. Conclusions: Psychosocial stress factors in families with infants and toddlers remained highly pronounced and even partly increased irrespective of pandemic events. The ongoing heightened support needs of families with young children must remain a focus and promoting infants’ mental health as well as strengthening a positive family microclimate should be a top priority in the aftermath of COVID-19. Trial registration: The study was pre-registered in OSF (https://osf.io/search/?q=tksh5&page=1). Keywords: Parent Psychosocial Functioning, Infant Mental Health, COVID-19, Depression, Anxiety, Early Life Adversity, Infancy and Early Childhood, Parenting, Stress, Pandemic
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://osf.io/tvfwx/" target="_blank">Easing pandemic-related restrictions, easing psychosocial stress factors in families with infants and toddlers? Cross-sectional results of the three wave CoronabaBY study from Germany.</a>
|
||
</div></li>
|
||
<li><strong>SARS-CoV-2 post-vaccine surveillance studies in Australian children and adults with cancer: SerOzNET Statistical Analysis Plan</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
COVID-19 disease is associated with higher morbidity and mortality in cancer patients. Our study aimed to characterize the optimal strategy to improve vaccine induced protection against COVID-19 in children and adolescents with cancer. Results from The SerOzNET study will contribute comprehensive data on serology, cellular immune correlates from functional T-cell assays, quality of life data, and associated toxicity in relation to COVID-19 vaccination in children and adults with cancer. In this plan, we describe the statistics that will be used to report results of the SerOzNET study. SerOzNET examines COVID-19 vaccine response in children and adolescents with cancer.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.26.23286261v1" target="_blank">SARS-CoV-2 post-vaccine surveillance studies in Australian children and adults with cancer: SerOzNET Statistical Analysis Plan</a>
|
||
</div></li>
|
||
<li><strong>COVID-19 or seasonal influenza? How to distinguish in people younger than 65 years old: A retrospective observational cohort study comparing the 2009 pandemic influenza A H1N1 with 2022 SARS-CoV-2 Omicron BA.2 outbreaks in China.</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Objective: This study attempted to explore the difference of clinical characteristics in H1N1 influenza infection and SARS-CoV-2 Omicron infection in people younger than 65 years old, in order to better identify the two diseases. Methods: A total of 127 H1N1 influenza patients diagnosed from May 2009 to July 2009 and 3265 patients diagnosed and identified as SARS-CoV-2 Omicron BA.2 variant from March 2022 to May 2022 were admitted in this study. Through the 1 : 2 match based on age (The difference is less than 2 years), gender and underlying diseases，115 patients with H1N1 infection and 230 patients with SARS-CoV-2 Omicron BA.2 infection (referred to as H1N1 group and Omicron group) were included in the statistics. The clinical manifestations of H1N1 group were compared with those of Omicron group. Logistic regression was performed to analyze the possible independent risk factors of H1N1 group and Omicron group. And multiple linear regression was used to analyze the factors for time for nucleic acid negativization (NAN) . Results: The median age of the two groups was 21 [11,26] years. Compared with the H1N1 group, the Omicron group had lower white blood cell count and CRP levels, less fever, nasal congestion, sore throat, cough, sputum and headache, while more olfactory loss, muscle soreness and LDH abnormalities. The Omicron group used less antibiotics and antiviral drugs, and the NAN time was longer (17 [ 14,20] VS 4 [ 3,5], P < 0.001). After logistic regression, it was found that fever, cough, headache, and increased white blood cell count were more correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more correlated with the Omicron group. After analyzing the factors of NAN time, it was found that fever (B 1.529, 95 % CI [0.149,2.909], P = 0.030) significantly predicted longer NAN time in Omicron patients. Conclusion: This study comprehensively evaluated the similarities and differences in clinical characteristics between SARS-CoV-2 Omicron infection and 2009 H1N1 influenza infection, which is of great significance for a better understanding for these diseases.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.28.23286466v1" target="_blank">COVID-19 or seasonal influenza? How to distinguish in people younger than 65 years old: A retrospective observational cohort study comparing the 2009 pandemic influenza A H1N1 with 2022 SARS-CoV-2 Omicron BA.2 outbreaks in China.</a>
|
||
</div></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
|
||
<ul>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: Aerobic exercise and strength training<br/><b>Sponsor</b>: Ukbe Sirayder<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluticasone; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Blood sampling<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: N-Acetylcysteine; Drug: Placebo<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Active, not recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: miRNA analysis in plasma<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telerehabilitation in the Post-COVID-19 Patient (TRIALS)</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Istituto Auxologico Italiano<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator<br/><b>Sponsor</b>: Hebei Medical University<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine</strong> - <b>Conditions</b>: Vaccine Reaction; COVID-19<br/><b>Interventions</b>: Biological: Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech); Biological: VidPrevtyn® Beta vaccine (Sanofi/GSK)<br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo<br/><b>Sponsor</b>: Westlake Pharmaceuticals (Hangzhou) Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B<br/><b>Interventions</b>: Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test; Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)<br/><b>Sponsors</b>: Medical Group Care, LLC; CSSi Life Sciences<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: Gamma Variant RBD-based ARVAC-CG vaccine; Biological: Omicron Variant RBD-based ARVAC-CG vaccine; Biological: Bivalent RBD-based ARVAC-CG vaccine; Other: Placebo<br/><b>Sponsors</b>: Mónica Edith Lombardo; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina; Laboratorio Pablo Cassará S.R.L.<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of HH-120 Nasal Spray in Close Contacts of Those Diagnosed With COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: HH-120 Nasal Spray<br/><b>Sponsor</b>: Beijing Ditan Hospital<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19<br/><b>Interventions</b>: Other: Individual Counseling; Other: Group Counseling; Other: Resources<br/><b>Sponsors</b>: New Mexico State University; National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Post COVID-19 REspiratory Mechanisms and the Efficacy of a Breathing Exercise Intervention for DYsregulated Breathing</strong> - <b>Conditions</b>: COVID-19; Respiratory Disease<br/><b>Intervention</b>: Other: Breathing techniques over 12 sessions / 6 weeks inc yoga<br/><b>Sponsor</b>: University of Nottingham<br/><b>Recruiting</b></p></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
||
<ul>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pinosrtobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism</strong> - Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants</strong> - Host-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N6-methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during a stress response. Gene expression profiles observed post-infection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dual mechanism: Epigenetic inhibitor apabetalone reduces SARS-CoV-2 Delta and Omicron variant spike binding and attenuates SARS-CoV-2 RNA induced inflammation</strong> - The SARS-CoV-2 virus initiates infection via interactions between the viral spike protein and the ACE2 receptors on host cells. Variants of concern have mutations in the spike protein that enhance ACE2 binding affinity, leading to increased virulence and transmission. Viral RNAs released after entry into host cells trigger interferon-I (IFN-I) mediated inflammatory responses for viral clearance and resolution of infection. However, overreactive host IFN-I responses and pro-inflammatory signals…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune evasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); molecular approaches</strong> - In December 2019, a new betacoronavirus, known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused an outbreak at the Wuhan seafood market in China. The disease was further named coronavirus disease 2019 (COVID-19). In March 2020, the World Health Organization (WHO) announced the disease to be a pandemic, as more cases were reported globally. SARS-CoV-2, like many other viruses, employs diverse strategies to elude the host immune response and/or counter immune responses. The…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro and in vivo suppression of SARS-CoV-2 replication by a modified, short, cell-penetrating peptide targeting the C-terminal domain of the viral spike protein</strong> - Peptides are promising therapeutic agents for COVID-19 because of their specificity, easy synthesis, and ability to be fine-tuned. We previously demonstrated that a cell-permeable peptide corresponding to the SARS-CoV-2 Spike C-terminal domain (CD) inhibits the interaction between viral spike and nucleocapsid proteins that results in SARS-CoV-2 replication in vitro. Here, we used docking studies to design R-t-Spike CD(D), a more potent short cell-penetrating peptide composed of all D-form amino…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of a screening platform to discover natural products active against SARS-CoV-2 infection using lung organoid models</strong> - CONCLUSION: This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19.</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants</strong> - SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351,…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 infection in cellular systems using engineered trimeric receptor-binding domain of spike protein</strong> - Here, we provide a protocol for the design, expression, purification, and functional studies of an engineered trimeric version of the receptor-binding domain (tRBD) of SARS-CoV-2 spike protein. We describe the use of tRBD to block SARS-CoV-2 spike pseudovirus and true virus binding to cellular angiotensin converting enzyme-2 (ACE2), thereby blocking viral infection. This protocol is applicable to generate a trimeric version of any protein of interest. For complete details on the use and…</p></li>
|
||
<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 Biodistribution of Nanoligomers Targeting the SARS-CoV-2 Genome for the Treatment of COVID-19</strong> - As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An approach combining deep learning and molecule docking for drug discovery of cathepsin L</strong> - CONCLUSION: Our approach enables drug discovery from large-scale databases with little computational consumption, which will save the cost and time required for drug discovery.</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Search of Novel Small Molecule Inhibitors for the Main Protease of SARS-CoV-2</strong> - The current outbreak of coronavirus disease 2019 (COVID-19) has prompted the necessity of efficient treatment strategies. The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Main protease (Mpro), also called 3-chymotrypsin-like protease (3CL protease), plays an essential role in cleaving virus polyproteins for the functional replication complex. Therefore, Mpro is a promising drug target for COVID-19 therapy. Through molecular modelling, docking…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19</strong> - COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy Validation of SARS-CoV-2-Inactivation and Viral Genome Stability in Saliva by a Guanidine Hydrochloride and Surfactant-Based Virus Lysis/Transport Buffer</strong> - To enhance biosafety and reliability in SARS-CoV-2 molecular diagnosis, virus lysis/transport buffers should inactivate the virus and preserve viral RNA under various conditions. Herein, we evaluated the SARS-CoV-2-inactivating activity of guanidine hydrochloride (GuHCl)- and surfactant (hexadecyltrimethylammonium chloride (Hexa-DTMC))-based buffer, Prep Buffer A, (Precision System Science Co., Ltd., Matsudo, Japan) and its efficacy in maintaining the stability of viral RNA at different…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel Tetrahydroisoquinoline-Based Heterocyclic Compounds Efficiently Inhibit SARS-CoV-2 Infection <em>In Vitro</em></strong> - The ongoing COVID-19 pandemic has caused over six million deaths and huge economic burdens worldwide. Antivirals against its causative agent, SARS-CoV-2, are in urgent demand. Previously, we reported that heterocylic compounds, i.e., chloroquine (CQ) and hydroxychloroquine (HCQ), are potent in inhibiting SARS-CoV-2 replication in vitro. In this study, we discussed the syntheses of two novel heterocylic compounds: tert-butyl…</p></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
||
|
||
|
||
<script>AOS.init();</script></body></html> |