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183 lines
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<title>14 May, 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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<ul>
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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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>BEHAVIOURS IN THE STOCK MARKET - AN EMPIRICAL STUDY</strong> -
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<div>
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This study has two main purposes. Its first purpose is to analyse the influence of sociodemographic characteristics and investment experience of individual and institutional investors on their investment behaviours in the stock market. The second purpose of the present paper is to study the impact of the investment behaviours on the investment decisions following the market selloff in March 2020 that preceded the emergence of COVID 19. Additionally, this study seeks to analyse the potential impact of the social distancing measures on the herd mentality influencing the investment decision.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/ypq8m/" target="_blank">BEHAVIOURS IN THE STOCK MARKET - AN EMPIRICAL STUDY</a>
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</div></li>
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<li><strong>Psychological Issues on Family Caregivers of Stroke Patients in Brunei Darussalam: In the Era of Pandemic Covid-19</strong> -
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<div>
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Family caregivers play an important role in providing main support for family members with a disability in order for them to function normally in their everyday life. The main goal of this research study is to promote psychological health awareness of stroke family caregivers in Brunei Darussalam, especially during the pandemic of Covid-19. This study concentrated particularly on long-term family caregivers who provide care to stroke family members who were severely affected by the disease that caused them to heavily depended on their family caretakers. This qualitative research involves interviewing 8 locals participants using snowballing sampling and a thematic analysis approach that investigate thoroughly the challenges and identifies the needs required by family caregivers in Brunei. The findings of the study discovered that all family caregivers experience psychological issues such as ‘Depression’ and ‘Stress’ and are in need of family support and self-care to reduce challenges they experience such as emotional exhaustion, physical problem, sleep deprivation, financial issues, and accessibility to basic needs in caregiving.
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</div>
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<div class="article- link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/4vce9/" target="_blank">Psychological Issues on Family Caregivers of Stroke Patients in Brunei Darussalam: In the Era of Pandemic Covid-19</a>
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</div></li>
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<li><strong>Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody</strong> -
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<div>
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The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 ug/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491770v1" target="_blank">Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody</a>
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</div></li>
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<li><strong>Three-doses of BNT162b2 COVID-19 mRNA vaccine establishes long-lasting CD8+ T cell immunity in CLL and MDS patients</strong> -
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<div>
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Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection related disease and mortality. To understand T cell immunity, its long-term persistence, and correlation with antibody response, we evaluated the BNT162b2 COVID 19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine- specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cell was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 vaccine-derived immunogenic epitopes were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491706v1" target="_blank">Three-doses of BNT162b2 COVID-19 mRNA vaccine establishes long-lasting CD8+ T cell immunity in CLL and MDS patients</a>
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</div></li>
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<li><strong>Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens</strong> -
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<div>
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The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID-19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS- CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491823v1" target="_blank">Humoral immunity to SARS- CoV-2 elicited by combination COVID-19 vaccination regimens</a>
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</div></li>
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<li><strong>In situ architecture and membrane fusion of SARS-CoV-2 Delta variant</strong> -
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<div>
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Among the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, the detailed mechanism of S-mediated membrane fusion remains elusive. Here we report the molecular assembly and fusion snapshots of the authentic Delta variant. Envelope invagination and fusion events were frequently observed. Native structures of pre- and postfusion S were determined up to 4.1-A resolution. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Based on these findings, we proposed a model for S-mediated membrane fusion and a model for the invagination formation.
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</div>
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<div class="article-link article-html- link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491759v1" target="_blank">In situ architecture and membrane fusion of SARS-CoV-2 Delta variant</a>
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</div></li>
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<li><strong>Optimality of Maximal-Effort Vaccination</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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It is widely acknowledged that vaccinating at maximal effort in the face of an ongoing epidemic is the best strategy to minimise infections and deaths from the disease. Despite this, no one has proved that this is guaranteed to be true if the disease follows multi-group SIR (Susceptible-Infected-Recovered) dynamics. This paper provides a novel proof of this principle for the existing SIR framework, showing that the total number of deaths or infections from an epidemic is decreasing in vaccination effort. Furthermore, it presents a novel model for vaccination which assumes that vaccines are distributed randomly to the unvaccinated population and suggests, using COVID-19 data, that this more accurately captures vaccination dynamics than the model commonly found in the literature. However, as the novel model provides a strictly larger set of possible vaccination policies, the results presented in this paper hold for both models.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.12.22275015v1" target="_blank">Optimality of Maximal-Effort Vaccination</a>
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</div></li>
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<li><strong>Higher contact among vaccinated can be a mechanism for negative vaccine effectiveness</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Evidence from early observational studies suggested negative vaccine effectiveness for the SARS-CoV-2 Omicron variant. Using transmission modeling, we illustrated how increased contact between vaccinated individuals, vaccinated contact heterogeneity, paired with lower vaccine efficacies could produce negative measurements and how we can identify this mechanism via a key temporal signature.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.25.22274266v3" target="_blank">Higher contact among vaccinated can be a mechanism for negative vaccine effectiveness</a>
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</div></li>
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<li><strong>Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The SARS-CoV-2 pandemic likely began by viral spillover from animals to humans1-3; today multiple animal species are known to be susceptible to infection4-8. White-tailed deer, Odocoileus virginianus are infected in North America at substantial levels9-11, and genomic data suggests that a variant in deer may have spilled back to humans12,13. Here we characterize SARS-CoV-2 in deer from Pennsylvania (PA) sampled during fall and winter 2021. Of 123 nasal swab samples analyzed by RT-qPCR, 20 (16.3%) were positive for SARS-CoV-2. Seven whole-genome sequences were obtained, together with six more partial spike sequences. These annotated as alpha and delta variants, the first reported observations of these lineages in deer, documenting multiple new jumps from humans to deer. The alpha lineage persisted in deer after its displacement by delta in humans, and deer-derived alpha variants diverged significantly from those in humans, consistent with a distinctive evolutionary trajectory in deer.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.02.17.22270679v4" target="_blank">Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania</a>
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</div></li>
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<li><strong>The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein</strong> -
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<div>
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The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, the Omicron/BA.2 lineage in early 2022. Here, we describe how Omicron BA.1 and BA.2 show a lower severity phenotype in a hamster model of pathogenicity which maps specifically to the spike gene. We further show that Omicron is attenuated in a lung cell line but replicates more rapidly, albeit to lower peak titres, in human primary nasal cells. This replication phenotype also maps to the spike gene. Omicron spike (including the emerging Omicron lineage BA.4) shows attenuated fusogenicity and a preference for cell entry via the endosomal route. We map the altered Omicron spike entry route and partially map the lower fusogenicity to the S2 domain, particularly the substitution N969K. Finally, we show that pseudovirus with Omicron spike, engineered in the S2 domain to confer a more Delta-like cell entry route retains the antigenic properties of Omicron. This shows a distinct separation between the genetic determinants of these two key Omicron phenotypes, raising the concerning possibility that future variants with large antigenic distance from currently circulating and vaccine strains will not necessarily display the lower intrinsic severity seen during Omicron infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.12.31.474653v2" target="_blank">The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein</a>
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</div></li>
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<li><strong>Using CATA and Machine Learning to Operationalize Old Constructs in New Ways: An Illustration Using U.S. Governors’ COVID-19 Press Briefings</strong> -
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<div>
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Increased computing power and greater access to online data have led to rapid growth in the use of computer-aided text analysis (CATA) and machine learning methods. Using “big data”, researchers have not only advanced new streams of research, but also new research methodologies. Noting this trend and simultaneously recognizing the value of traditional research methods, we lay out a methodology that bridges the gap between old and new approaches to operationalize old constructs in new ways. With a combination of web scraping, CATA, and supervised machine learning, using labeled ground truth data (i.e., data with known inputs and outputs), we train a model to predict CIP (Charismatic-Ideological- Pragmatic) leadership styles from running text. To illustrate this method, we apply the model to classify U.S. state governors’ COVID-19 press briefings according to their CIP leadership style. In addition, we demonstrate content and convergent validity of the method.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/84ux5/" target="_blank">Using CATA and Machine Learning to Operationalize Old Constructs in New Ways: An Illustration Using U.S. Governors’ COVID-19 Press Briefings</a>
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</div></li>
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<li><strong>Pregnancies and contraceptive use in four African countries during the COVID-19 pandemic</strong> -
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<div>
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The COVID-19 pandemic and the public health measures adopted in response to it have triggered plenty of speculation about the potential impact on fertility in different regions of the globe. This study provides evidence on the fertility response in four sub-Saharan African countries during the first year of the pandemic. Using harmonized data on women of childbearing age from the Performance Monitoring for Action (PMA) data series, this study compares pregnancy rates by the turn of the year 2020/21 to a pre-pandemic baseline. There is no indication of a general increase in pregnancy rates since the beginning of the pandemic. In some of the sample countries, pregnancy rates during COVID-19 have instead fallen significantly among the youngest and the least educated women of childbearing age, respectively. In parallel, rates of modern contraceptive usage have risen significantly among the surveyed female populations in several sample countries.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/av7ec/" target="_blank">Pregnancies and contraceptive use in four African countries during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling</strong> -
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<div>
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Objectives: The coronavirus disease-19 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the molecular and cellular levels, the SARS-Cov-2 uses its envelope glycoprotein, the spike S protein, to infect the target cells in the lungs via binding with their transmembrane receptor, the angiotensin- converting enzyme 2 (ACE2). Here, we wanted to invesitgate if other molecular targets and pathways may be used by SARS- Cov-2. Methods: We investigated the possibility for the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation was examined upon cell treatment with the recombinant full spike 1 S protein or RBD. Results: We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical ERK1/2 and AKT kinases and an increase of survivin expression controlling the survival pathway. Conclusions: Our study suggests the putative implication of EGFR and its related signaling pathways in SARS-CoV-2 infectivity and Covid-19 pathology. This may open new perspectives in the treatment of Covid-19 patients by targeting EGFR.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.10.491351v1" target="_blank">The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling</a>
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</div></li>
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<li><strong>Biochemical Characterization of Emerging SARS-CoV-2 Nsp15 Endoribonuclease Variants</strong> -
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<div>
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Global sequencing efforts from the ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, continue to provide insight into the evolution of the viral genome. Coronaviruses encode 16 nonstructural proteins, within the first two-thirds of their genome, that facilitate viral replication and transcription as well as evasion of the host immune response. However, many of these viral proteins remain understudied. Nsp15 is a uridine-specific endoribonuclease conserved across all coronaviruses. The nuclease activity of Nsp15 helps the virus evade triggering an innate immune response. Understanding how Nsp15 has changed over the course of the pandemic, and how mutations affect its RNA processing function, will provide insight into the evolution of an oligomerization-dependent endoribonuclease and inform drug design. In combination with previous structural data, bioinformatics analyses of 1.9+ million SARS-CoV-2 sequences revealed mutations across Nsp15’s three structured domains (N-terminal, Middle, EndoU). Selected Nsp15 variants were characterized biochemically and compared to wild type Nsp15. We found that mutations to important catalytic residues decreased cleavage activity but increased the hexamer/monomer ratio of the recombinant protein. Many of the highly prevalent variants we analyzed led to decreased nuclease activity as well as an increase in the inactive, monomeric form. Overall, our work establishes how Nsp15 variants seen in patient samples affect nuclease activity and oligomerization, providing insight into the effect of these variants in vivo.
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</div>
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<div class="article-link article- html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.10.491349v1" target="_blank">Biochemical Characterization of Emerging SARS-CoV-2 Nsp15 Endoribonuclease Variants</a>
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</div></li>
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<li><strong>Low immune response after 1.5 years of primary SARS-CoV-2 infection and Covishield vaccination lead to SARS-CoV-2 reinfection</strong> -
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<div>
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We have investigated six COVID recovered cases with two doses of Covishield vaccination followed by reinfection. The primary SARS-CoV-2 infection found to occur with B.1 and reinfection with Omicron BA.1 and BA.2 variants. The genomic characterization and duration between two infections confirms these cases as SARS-CoV-2 reinfection. The mutation analysis of the reinfection cases correlated with immune evasion potential of BA.1 and BA.2 sub lineages. The immune response determined at different time intervals demonstrated boost post two dose vaccination, decline in pre- reinfection sera post 7 months and rise post reinfection. Apparently, these cases suffered from SARS-CoV-2 reinfection with the declined hybrid immunity acquired from primary infection and two dose covishield vaccination. This suggests the need for booster dose of vaccination. Besides this, multiple non-pharmaceutical interventions should be used to cope up with SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.12.491584v1" target="_blank">Low immune response after 1.5 years of primary SARS-CoV-2 infection and Covishield vaccination lead to SARS-CoV-2 reinfection</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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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 Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)<br/><b>Sponsors</b>: University of California, Irvine; Hudson Valley Healing Arts 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>Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-9199; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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Sorrento Therapeutics, Inc.<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>A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Shulan (Hangzhou) Hospital<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>Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Radiation: [18F]DPA-714 positron emission tomography (PET) scan<br/><b>Sponsors</b>: Amsterdam UMC, location VUmc; ZonMw: The Netherlands Organisation for Health Research and Development<br/><b>Enrolling by invitation</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>Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Palbociclib<br/><b>Sponsor</b>: biotx.ai GmbH<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>Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics Inc.<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>Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics Inc.<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>To Evaluate SSD8432/Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 dose; Drug: SSD8432 placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<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>THEMBA II T-Cell Vaccine: A Phase 1/2 Study of Vaccination With saRNA COVID-19 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AAHI-SC2 Vaccine; Biological: AAHI- SC3 Vaccine; Biological: EUA or approved vaccine<br/><b>Sponsor</b>: ImmunityBio, 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>The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Chinese herbal medicine<br/><b>Sponsor</b>: <br/>
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Hong Kong Baptist 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>Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 dose1; Drug: SSD8432 dose2; Drug: SSD8432Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<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>To Evaluate SSD8432/ Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>: COVID-19 Patients<br/><b>Interventions</b>: Drug: SSD8432 dose 1/Ritonavir; Drug: SSD8432 dose 2<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<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, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Wuhan Recogen Biotechnology Co., Ltd.<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>Home-based Exercise Program in Patients With the Post-COVID-19 Condition</strong> - <b>Conditions</b>: Long COVID; Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: Home- based physical training<br/><b>Sponsor</b>: University of Sao Paulo<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>Kesuting Syrup in the Treatment of Corona Virus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Cough<br/><b>Interventions</b>: Drug: Kesuting syrup; Drug: LianHuaQingWen Granules<br/><b>Sponsor</b>: Guizhou Bailing Group Pharmaceutical Co Ltd<br/><b>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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<ul>
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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 and Hippo Signaling Pathway: A Potential Therapeutic Target</strong> - SARS-CoV-2 is responsible for the ongoing COVID-19 pandemic, which causes respiratory failure and damage to multiple organ systems. Emergence of new variants of concern (VOCs), including Omicron can potentially render the current vaccines ineffective. However, our understanding of COVID-19 pathophysiology and molecular basis of SARS-CoV-2 infection is very limited. The role of the Hippo signaling pathway, an evolutionarily conserved organogenesis circuitry, in tissue inflammation and innate…</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>GPR68 Inhibition with a Novel Group of Ogremorphin Inhibitors Upregulate Endothelial Barrier Function and Protect Against Bacterial Pathogens or Acidosis-induced Inflammation in Lung Endothelium</strong> - CONCLUSION: Altogether, these results establish an essential role of GPR68 in endothelial dysfunction and strongly suggest a therapeutic potential of GPR68-selective inhibitors in improving endothelial dysfunction-derived lung injuries.</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>A Protein Tyrosine Phosphatase 4A3 (PTP4A3) inhibitor prevents and repairs pulmonary endothelial barrier dysfunction and ameliorates acute lung injury provoked by the SARS-CoV-2 Spike protein subunit 1 in k18-hACE2 transgenic mice</strong> - PTP4A3 regulates various inflammatory and cytoskeletal signaling pathways (e.g., STAT3, RhoA, ERK, AKT) that are involved in endothelial barrier dysfunction and acute lung injury (ALI). We have investigated the actions of JMS-053, a small PTP4A3 inhibitor, in both in vitro and in vivo models of SARS-CoV-2 Spike protein subunit 1 (S1SP)-induced endothelial inflammation and acute lung injury. S1SP (10nM) caused a time-dependent endothelial barrier dysfunction in human lung microvascular…</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>Formulation and Testing of Alcohol-based Hand Sanitizers</strong> - The pandemic caused as a result of Covid-19 brought awareness to the use of hand sanitizers around the world. Maintaining hand hygiene has been confirmed to be critical for diminishing the colonization and incidence of infectious diseases. The objective of this study was to create a formulation of alcohol-based hand sanitizer that is effective at reducing the presence of microorganisms. A comparative assessment of antimicrobial efficacy of different hand sanitizers was used to compare two…</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>Drug repurposing: A novel therapeutic approach for pancreatic cancer</strong> - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a survival rate of 10%. It is projected to be the second leading cause of cancer related deaths in USA by 2030. The therapeutic development against PDAC has been slow and chemotherapeutic resistance for available treatment options is a significant problem. Over the past few years, drug repurposing has shown promise as a fast, economic and reliable strategy to develop novel treatment options for most of the diseases. The…</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>Synthesis of the transmembrane domain of the spike protein from SARS-CoV-2 using solid phase peptide synthesis and determination of its oligomerization state</strong> - As of today, nearly six hundred thousand lives have been lost to the disease COVID-19 in the United States alone. This highly contagious disease has a proposed R(0) value of 5.7, meaning that for every person infected, they transmit the virus to about 5 other people. This has caused researchers to expeditiously study Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Due to the state of the current pandemic, the distribution of effective vaccination and antiviral medication is…</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>Dietary Empagliflozin Regulates Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in Kidney Cortex of Mice</strong> - Persons with type 2 diabetes mellitus (T2D) are at greater risk for poor prognosis, including renal pathology, when infected with Covid-19 virus. A newer class of medications for T2D is the gliflozin class, including Empagliflozin (EMPA), which inhibits the renal proximal tubule sodium glucose cotransporter, type 2 (SGLT2) resulting in glucosuria and reduction in hyperglycemia. Whether these medications alter susceptibility and responses to Covid-19, and similar infections, is not known. The…</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 Botanical Viral Entry Inhibitors for SARS-CoV-2</strong> - The examination of biodiversity across the world has historically been a critical part of drug development and led to the discovery of common medications for many medical issues including pain management, cancer, heart disease, and infections. During the SARS-CoV-2 pandemic, the use of natural supplements in the United States has increased. The efficacy of these natural products to prevent SARS-CoV-2 infection and the safety of their use remains unexplored; therefore, more research must be done…</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 biochemistry students virtually utilizing problem-based learning and at home lab activities</strong> - The unprecedented 2020 COVID-19 pandemic prompted the rapid shift to online learning in higher education. For courses particularly in the natural sciences, this shift posed a challenge to adapt complex course material that relied on in- person demonstrations and hands-on laboratory experiences to successfully be mastered. Online learning continues grow in these fields where it was once limited. In this piece, we describe the rejuvenation of our problem-based learning Introduction to Biochemistry…</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>Alcohol-based Hand Sanitizer: Comparing Formulations to Aggressively withstand Bacteria</strong> - Due to Covid-19, satisfactory hand washing/hygiene is more vital than ever. And realistically people do not always get up to wash their hand with soap and water every single time. People look for easy access which is hand sanitizer. In this study two formulation of alcohol-based hand sanitizers both contain 75% Isopropyl Alcohol but formulation #1 has 30% Hydrogen Peroxide. Testing the formulations effectiveness by comparing it to other store brand hand sanitizers (Germ X, Walgreens, Bath 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>Disruption of ATG9A-dependent basal autophagy causes an accumulation of ubiquitin-rich condensates which act as a platform for inflammatory signaling</strong> - Excessive inflammation underlies many human diseases, such as neurodegeneration, autoimmune disorders, cancer, and COVID-19. Thus, cellular mechanisms that control inflammation are of high therapeutic interest. Autophagy has been implicated in the suppression of inflammation, yet mechanistic links between autophagy and inflammation are not completely understood. Previous work demonstrated that loss of ATG9A, but not ATG5 or ATG7, increased inflammatory signaling through the STING-IRF3 cascade,…</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>Synthesis of the transmembrane domain of the accessory protein ORF7a of SARS-CoV-2 using solid phase peptide synthesis and analyzing the oligomerization state</strong> - This research project consists of synthesizing and characterizing the accessory protein ORF7a of SARS-CoV-2. ORF7a plays a role in viral assembly and inhibition of this protein would prevent viruses from assembling and spreading within a host’s cells. The goal of this project is to determine the oligomerization state of the protein through a fluorescence assay, which would determine the protein’s structure and how it folds. After determining the oligomerization state of the protein, potential…</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 Discovery of Antivirals and Targets for SARS-CoV-2 and EV-A71</strong> - Positive Strand RNA (PSR) viruses, such as coronaviruses and enteroviruses, cause serious health and economic threats worldwide, as currently seen with the COVID-19 pandemic. This has drawn attention to the importance of identifying new antivirals and molecular targets in RNA viruses. The multifunctionality of PSR genomes make them desirable targets for therapeutic intervention. Here, we present a class of antivirals that can inhibit SARS-CoV-2 replication in vitro by targeting conserved viral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A High throughput bioluminescent assay to monitor the activity of COVID-19 Methyltransferases Capping Enzymes</strong> - The recent pandemic outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) was first reported in Wuhan, China in late 2019 resulting in infection of over 259 million and death of over 5.17 world-wide as of November</li>
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</ul>
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<ol start="2021" type="1">
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">In the USA, the number of diagnosed individuals reached 48 million with 92,000 Death cases. Despite the lower pathogenicity compared to SARS-CoV and MERS-CoV, the high infection rate of SARS-CoV-2 results in large numbers of hospitalizations and deaths…</li>
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</ol>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Binding mechanisms of Shikonin derivatives targeting SARS-CoV-2 main protease</strong> - Shikonin, a well-known bioactive chemical present in the dried roots of Lithospermum erthrorhizon, is recognized for its broad-spectrum activities against cancer, oxidative stress, inflammation, virus, and anti-COVID-19 agent. In recent discovery, the crystallographic study of Shikonin bound Main protease (M^(pro) ) of SARS CoV-2 revealed different conformation, suggesting the possibility of designing Shikonin derivatives as potential inhibitors of Covid. Towards the goal, the present study is…</li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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