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<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>Rapid Assessment of the Potential Paucity and Price Increases for Suggested Medicines and Protection Equipment for COVID-19 Across Developing Countries With a Particular Focus on Africa and the Implications</strong> -
<div>
Countries across Africa and Asia have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE). However, there has been considerable controversy surrounding some treatments including hydroxychloroquine where the initial hype and misinformation led to shortages, price rises and suicides. Price rises and shortages were also seen for PPE. Such activities can have catastrophic consequences especially in countries with high copayment levels. Consequently, there is a need to investigate this further.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/vyrqk/" target="_blank">Rapid Assessment of the Potential Paucity and Price Increases for Suggested Medicines and Protection Equipment for COVID-19 Across Developing Countries With a Particular Focus on Africa and the Implications</a>
</div></li>
<li><strong>Occupational and environmental exposure to SARS-CoV-2 in and around infected mink farms</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Uncontrolled SARS-CoV-2 infections in farmed minks raised immediate concerns regarding human health which initiated intensive environmental investigations. Air sampling was performed in infected mink farms, at farm premises and at residential sites. A range of other environmental samples were collected from minks9 housing units. Inside the farms, high levels of SARS-CoV-2 RNA were found in airborne dust, on surfaces, and on various other environmental matrices. This warns for occupational exposure which was substantiated by considerable SARS-CoV-2 RNA concentrations in personal air samples. Dispersion of SARS-CoV-2 to outdoor air was found to be limited and SARS-CoV-2 RNA was not detected in air samples collected beyond farm premises, implying a negligible environmental exposure risk for nearby communities. Our occupational and environmental risk assessment is in line with whole genome sequences analyses showing mink-to-human transmission in farm workers, but no indications for direct zoonotic transmission events to nearby communities.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.06.20248760v1" target="_blank">Occupational and environmental exposure to SARS-CoV-2 in and around infected mink farms</a>
</div></li>
<li><strong>Magnitude, change over time, demographic characteristics and geographic distribution of excess deaths among nursing home residents during the first wave of COVID-19 in France: a nationwide cohort study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Importance: Nursing home (NH) residents are particularly vulnerable to SARS-CoV-2 infections and coronavirus disease 2019 (COVID-19) lethality. However, excess deaths in this population have rarely been documented. Objectives: The primary objective was to assess the number of excess deaths among NH residents during the first wave of the COVID-19 pandemic in France. The secondary objectives were to determine the number of excess deaths as a proportion of the total excess deaths in the general population and determine whether a harvesting effect was present. Design: We studied a cohort of 494,753 adults (as of March 1st, 2020) aged 60 and over in 6,515 NHs in mainland France. This cohort was exposed to the first wave of the COVID-19 pandemic (from March 1st to May 31st, 2020) and was compared with the corresponding, reference cohorts from 2014 to 2019 (using data from the French National Health Data System). Main outcome and measures: The main outcome was all-cause death. Weekly excess deaths and standardized mortality ratios (SMRs) were estimated. Result: There were 13,505 excess deaths among NH residents. Mortality increased by 43% (SMR: 1.43). The mortality excess was higher among males than among females (SMR: 1.51 and 1.38, respectively) and decreased with age (SMRs in females: 1.61 in the 60-74 age group, 1.58 for 75-84, 1.41 for 85-94, and 1.31 for 95 or over; Males: SMRs: 1.59 for 60-74, 1.69 for 75-84, 1.47 for 85-94, and 1.41 for 95 or over). We did not observe a harvesting effect (up until August 30th, 2020). By extrapolating to all NH residents nationally (N=570,003), the latter accounted for 51% of the total excess deaths in the general population (N=15,114 out of 29,563). Conclusion: NH residents accounted for about half of the total excess deaths in France during the first wave of the COVID-19 pandemic. The excess death rate was higher among males than females and among younger residents than among older residents. We did not observe a harvesting effect. A real-time mortality surveillance system and the identification of individual and environmental risk factors might help to design the future model of care for older dependent adults.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.09.20248472v1" target="_blank">Magnitude, change over time, demographic characteristics and geographic distribution of excess deaths among nursing home residents during the first wave of COVID-19 in France: a nationwide cohort study</a>
</div></li>
<li><strong>Modeling the COVID-19 transmission in Italy: The roles of asymptomatic cases, social distancing, and lockdowns</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The SEIR model of COVID-19 is developed based on the system dynamics approach. Compared with existing models, the model successfully reproduces similar multiple observed outputs such as infected and recovered patients in Italy by July 2020. In doing so, the system dynamics model captures the roles of undocumented cases on the Italian COVID-19 flow. The model also considers two types of measures including behavioral measures and lockdown measures as they are embedded in the model. It is hoped that the model can enhance our understanding of the roles of undocumented cases, so-called asymptomatic cases, and the efficacy of two different policies on the COVID-19 flow. This study concludes that the first policy is important once the number of infected cases is relatively low. However, once the number of infected cases is very high so the society cannot identify infected and disinfected people, the second policy must be applied soon. It is thus this study suggests that relaxed lockdowns lead the second wave of the COVID-19 around the world.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.08.21249273v1" target="_blank">Modeling the COVID-19 transmission in Italy: The roles of asymptomatic cases, social distancing, and lockdowns</a>
</div></li>
<li><strong>Online search trends and word-related emotional response during COVID-19 lockdown in Italy - Preprint</strong> -
<div>
Italy was the first Western country with numerous COVID-19 infections that underwent a strong lockdown. This represents the first threat-related mass isolation in the history that can be in-depth studied by scientists to understand the side effects of pandemic lockdown in the psychophysical domain. There is increasing evidence that Italian lockdown was associated with larger incidence of stress, anxiety, and mood symptoms. It was thus expected that, at a more basic level, also emotion perception -namely how an individual judges the affective content of common words- changed substantially during lockdown, especially in individuals with high COVID-19 fear and high negative affect. We measured the effects of this long-term isolation and the related pandemic phobia in an online survey on 71 healthy Italian participants. They completed the Positive and Negative Affect Schedule and Fear of COVID-19 Scale and judged valence, arousal, and dominance of words either related or unrelated to COVID-19, as identified by Google search trends. We found that lockdown imposed by the COVID-19 epidemic had a substantial impact on participants emotional responses. Moreover, emotional judgments changes from normative data varied depending on word type and individuals emotional state, revealing early signals of individuals mental distress to COVID-19 confinement. Lower valence and dominance judgments were given only to COVID-19-related words by individuals with less negative feelings and COVID-19 fear, but also to COVID-19-unrelated words by individuals with more negative feelings and COVID-19 fear. Moreover, arousal judgments for all words decreased and increased, respectively, for individuals with less and more negative feelings and COVID-19 fear. With respect to more direct but demanding and expensive tools such as surveys and questionnaires, the methods used here allow to measure more conveniently but reliably the emotional alteration and clinical psychiatric risk of population through the analysis of word use in the web and their affective connotation.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/kp5gs/" target="_blank">Online search trends and word-related emotional response during COVID-19 lockdown in Italy - Preprint</a>
</div></li>
<li><strong>Challenges of e-Learning during the COVID-19 Pandemic Experienced by EFL Learners</strong> -
<div>
COVID-19 has disrupted most of the industries in the world. Education is the only industry that is completely transferred to online mode in most countries around the world. Online learning was the best solution for continuing education during the pandemic, especially in tertiary education. This study aims to determine the challenges and obstacles confronted by English language learners (EFL) in Science and Arts College, Alula, Taibah University, Saudi Arabia, during switching to online learning in the second semester of 2020 due to the COVID-19 pandemic. The contribution of this study is to evaluate the learners new experiences in online education and to assess the feasibility of the virtual methods of learning. This is achieved by analyzing 184 learners responses to the survey-based questionnaire. A descriptive statistical method was used to test the validation of the study. It is found that the main problems that influence and impact online EFL learning during COVID-19 are related to technical, academic, and communication challenges. The study results show that most EFL learners are not satisfied with continuing online learning, as they could not fulfill the expected progress in language learning performance.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/258cd/" target="_blank">Challenges of e-Learning during the COVID-19 Pandemic Experienced by EFL Learners</a>
</div></li>
<li><strong>In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea.</strong> -
<div>
Special Infectious Agent Unit in King Fahd Medical Research Center at King Abdulaziz University, Jeddah, Saudi Arabia, has pursed the anti-viral project field to optimize the group of medicinal plants for human-infectious diseases. We have begun virtually in this field since COVID-19 pandemic, besides our divergence in the infectious agents. In this study and based on the previous review, Hypericum perforatum (St. Johns Wort) and Echinacea (gaia HERBS) were tested in vitro using Vero E6 cells for their anti-viral effects against the newly identified Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) through its infectious cycle from 0 to 48 hours post infection. The hypericin (0.9 mg) of H. perforatum and the different parts (roots, seeds, aerial) of two types of Echinacea species (Echinacea purpurea and Echinacea angustifolia) were examined their efficacy in certain concentration and under light-dependent anti-viral activities to measure the inhibition of the SARS-CoV-2 mRNA expression of RNA-dependent RNA polymerase (RdRP) gene and the viral load with quantitative real-time polymerase chain reaction (qRT-PCR), and to assess the neutralization of the SARS-CoV-2 spike receptor binding on cell culture assay. Interestingly, the mixture (H.E.) of 100 mg/mL of H. perforatum and Echinacea was tested too on SARS-CoV-2 and showed crucial anti-viral activity competing H. perforatum then Echinacea effects as anti-viral treatment. Therefore, the results of gaia HERBS products, H. perforatum and Echinacea species, applied in this study showed significant anti-viral and virucidal effects in the following order of potency: H. perforatum, H.E., and Echinacea on SARS-CoV-2 infectious cycle; and will definitely required a set up of clinical trial with specific therapeutic protocol based on the outcome of this study.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.11.426295v1" target="_blank">In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea.</a>
</div></li>
<li><strong>Using image-based haplotype alignments to map global adaptation of SARS-CoV-2</strong> -
<div>
Quantifying evolutionary change among viral genomes is an important clinical device to track critical adaptations geographically and temporally. We built image-based haplotype-guided evolutionary inference (ImHapE) to quantify adaptations in expanding populations of non-recombining SARS-CoV-2 genomes. By combining classic population genetic summaries with image-based deep learning methods, we show that different rates of positive selection are driving evolutionary fitness and dispersal of SARS-CoV-2 globally. A 1.35-fold increase in evolutionary fitness is observed within the UK, associated with expansion of both the B.1.177 and B.1.1.7 SARS-CoV-2 lineages.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.426571v1" target="_blank">Using image-based haplotype alignments to map global adaptation of SARS-CoV-2</a>
</div></li>
<li><strong>Rigid monoclonal antibodies improve detection of SARS-CoV-2 nucleocapsid protein</strong> -
<div>
Monoclonal antibodies (mAbs) are the basis of treatments and diagnostics for pathogens and other biological phenomena. We conducted a structural characterization of mAbs against the N-terminal domain of nucleocapsid protein (NPNTD) from SARS-CoV-2 using small angle X-ray scattering (SAXS). Our solution-based results distinguished the mAbs' flexibility and how this flexibility impacts the assembly of multiple mAbs on an antigen. By pairing two mAbs that bind different epitopes on the NPNTD, we show that flexible mAbs form a closed sandwich-like complex. With rigid mAbs, a juxtaposition of the Fabs is prevented, enforcing a linear arrangement of the mAb pair, which facilitates further mAb polymerization. In a modified sandwich ELISA, we show the rigid mAb-pairings with linear polymerization led to increased NPNTD detection sensitivity. These enhancements can expedite the development of more sensitive and selective antigen-detecting point-of-care lateral flow devices (LFA), key for early diagnosis and epidemiological studies of SARS-CoV-2 and other pathogens.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.426597v1" target="_blank">Rigid monoclonal antibodies improve detection of SARS-CoV-2 nucleocapsid protein</a>
</div></li>
<li><strong>Fatal neuroinvasion of SARS-CoV-2 in K18-hACE2 mice is partially dependent on hACE2 expression</strong> -
<div>
Animal models recapitulating the distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. However, the cause(s) and mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection for up to 14 days post-infection. Despite infection and moderate inflammation in the lungs, lethality was invariably associated with viral neuroinvasion and neuronal damage (including spinal motor neurons). Neuroinvasion occurred following virus transport through the olfactory neuroepithelium in a manner that was only partially dependent on hACE2. Interestingly, SARS-CoV-2 tropism was overall neither widespread among nor restricted to only ACE2-expressing cells. Although our work incites caution in the utility of the K18-hACE2 model to study global aspects of SARS-CoV-2 pathogenesis, it underscores this model as a unique platform for exploring the mechanisms of SARS-CoV-2 neuropathogenesis.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.425144v1" target="_blank">Fatal neuroinvasion of SARS-CoV-2 in K18-hACE2 mice is partially dependent on hACE2 expression</a>
</div></li>
<li><strong>Emergence and Evolution of a Prevalent New SARS-CoV-2 Variant in the United States</strong> -
<div>
Genomic virus surveillance can lead to early identification of new variants and inform proper response during a pandemic. Using this approach, we have identified a new variant of the SARS-CoV-2 virus that emerged in the United States (U.S.) early in the coronavirus disease (COVID-19) pandemic and has become one of the most prevalent U.S variants. This new variant within the B.1.2 lineage referred to here as 20C-US, has not yet spread widely to other countries. The earliest 20C-US genomes can be traced to the southern U.S. in late May of 2020. A major early event was the rapid acquisition of five non-synonymous mutations. The changes carried by 20C-US now include mutations to genes involved in virus particle maturation and release, processing of viral proteins, and RNA genome integrity and translation genes, all important for efficient and accurate virus production. In addition, 20C-US has since acquired two new non-synonymous mutations that highlight its ongoing evolution, one of which is a Q677H mutation in the spike protein adjacent to the furin cleavage site. We predict that 20C-US may already be the most dominant variant of SARS-CoV-2 in the U.S. The ongoing evolution of 20C-US, as well as other dominant region-specific variants emerging around the world, should continue to be monitored with genomic, epidemiologic, and experimental studies to understand viral evolution and predict future outcomes of the pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.11.426287v1" target="_blank">Emergence and Evolution of a Prevalent New SARS-CoV-2 Variant in the United States</a>
</div></li>
<li><strong>An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia</strong> -
<div>
The current SARS-CoV-2 pandemic has emphasized the vulnerability of human populations to novel viral pressures, despite the vast array of epidemiological and biomedical tools now available. Notably, modern human genomes contain evolutionary information tracing back tens of thousands of years, which may help identify the viruses that have impacted our ancestors -- pointing to which viruses have future pandemic potential. Here, we apply evolutionary analyses to human genomic datasets to recover selection events involving tens of human genes that interact with coronaviruses, including SARS-CoV-2, that likely started more than 20,000 years ago. These adaptive events were limited to the population ancestral to East Asian populations. Multiple lines of functional evidence support an ancient viral selective pressure, and East Asia is the geographical origin of several modern coronavirus epidemics. An arms race with an ancient coronavirus, or with a different virus that happened to use similar interactions as coronaviruses with human hosts, may thus have taken place in ancestral East Asian populations. By learning more about our ancient viral foes, our study highlights the promise of evolutionary information to better predict the pandemics of the future. Importantly, adaptation to ancient viral epidemics in specific human populations does not necessarily imply any difference in genetic susceptibility between different human populations, and the current evidence points toward an overwhelming impact of socioeconomic factors in the case of COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.11.16.385401v2" target="_blank">An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia</a>
</div></li>
<li><strong>Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals a Broad Potential Host Range of SARS-CoV-2</strong> -
<div>
The pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health threat. Epidemiological studies suggest that bats are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. It has been shown that human, palm civet, pig and bat ACE2 can support virus entry, while the murine ortholog cannot. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. We found that ACE2 is expressed in a wide range of species, with especially high conservation in mammals. By analyzing amino acid residues of ACE2 critical for virus entry, based on structure of SARS-CoV spike protein interaction with human, bat, palm civet, pig and ferret ACE2, we identified approximately eighty ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. Functional assays showed that 44 of these mammalian ACE2 orthologs, including those of domestic animals, pets, livestock, and animals commonly found in zoos and aquaria, could bind SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind SARS-CoV-2 spike protein and support viral entry. We further identified the genetic determinant of New World monkey ACE2 that restricts viral entry using genetic and functional analyses. In summary, our study demonstrates that ACE2 from a remarkably broad range of species can facilitate SARS-CoV-2 entry. These findings highlight a potentially broad host tropism of SARS-CoV-2 and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, underscoring the necessity to monitor susceptible hosts to prevent future outbreaks.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.04.22.046565v4" target="_blank">Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals a Broad Potential Host Range of SARS-CoV-2</a>
</div></li>
<li><strong>Ineffectual AEC1 Differentiation from KRT8hi Transitional Cells without Fibrosis Associated with Fatal Acute Respiratory Failure in COVID-19 ARDS</strong> -
<div>
COVID-19 ARDS is associated with prolonged ventilator dependence and high mortality, but the underlying mechanisms are unknown. Critical to the pathogenesis of ARDS is injury to the alveolar epithelial cell (AEC) barrier; clinical recovery requires epithelial regeneration. We previously identified a KRT8hi transitional state that regenerating AEC2s adopt during differentiation into AEC1s, the persistence of which may be pathogenic in pulmonary fibrosis. Here, we hypothesize that ineffectual differentiation of transitional cells into AEC1s without fibrosis may underlie ongoing barrier permeability and poor clinical outcomes in COVID-19 ARDS. To test this hypothesis, we examined postmortem lung tissue of COVID-19 ARDS patients. We observed severe epithelial injury, AEC2 proliferation, and abundant transitional cells but ineffectual AEC1 differentiation. Transitional cells were cuboidal, partially spread, or flat and adherent to alveolar septa that were denuded of AEC1s but structurally normal without fibrosis. We conclude that ineffectual AEC1 differentiation from transitional AECs may underlie ongoing barrier permeability and poor clinical outcomes in COVID-19 ARDS. However, in contrast to fibrosis, transitional cells may retain the capacity for AEC1 differentiation with restoration of normal alveolar architecture and function. Novel therapies that promote differentiation of transitional cells into AEC1s may accelerate barrier restoration and clinical recovery in ARDS.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.12.426404v1" target="_blank">Ineffectual AEC1 Differentiation from KRT8hi Transitional Cells without Fibrosis Associated with Fatal Acute Respiratory Failure in COVID-19 ARDS</a>
</div></li>
<li><strong>Distinct lung-homing receptor expression and activation profiles on NK cell and T cell subsets in COVID-19 and influenza</strong> -
<div>
Respiratory viral infections with SARS-CoV-2 or influenza viruses commonly induce a strong infiltration of immune cells into the lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, little is known about how blood natural killer (NK) cells and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Using 28-colour flow cytometry and re-analysis of published RNA-seq datasets, we provide a detailed comparative analysis of NK cells and T cells in peripheral blood from moderately sick COVID-19 and influenza patients, focusing on the expression of chemokine receptors known to be involved in leukocyte recruitment to the lung. The results reveal a predominant role for CXCR3, CXCR6, and CCR5 in COVID-19 and influenza patients, mirrored by scRNA-seq signatures in peripheral blood and bronchoalveolar lavage from publicly available datasets. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation as compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza as compared to COVID-19. Together, our results indicate migration of functionally competent CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells to the lungs in moderate COVID-19 and influenza patients, identifying potential common targets for future therapeutic interventions in respiratory viral infections.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.426553v1" target="_blank">Distinct lung-homing receptor expression and activation profiles on NK cell and T cell subsets in COVID-19 and influenza</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>Dexamethasone for COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Drug: Dexamethasone<br/><b>Sponsor</b>:   University of Oklahoma<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>A Study of ORTD-1 in Patients Hospitalized With COVID-19 Related Pneumonia</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: ORTD-1 low dose;   Drug: ORTD-1 mid dose;   Drug: ORTD-1 high dose;   Other: Vehicle control<br/><b>Sponsor</b>:   Oryn Therapeutics, LLC<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>Rapid Diagnosis of COVID-19 by Chemical Analysis of Exhaled Air</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Diagnostic Test: Performance evaluation (sensitivity and specificity) for COVID-19 diagnosis of the Vocus PTR-TOF process<br/><b>Sponsor</b>:   Hospices Civils de Lyon<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>IMUNOR® Preparation in the Prevention of COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Drug: IMUNOR<br/><b>Sponsor</b>:   University Hospital Ostrava<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>A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adult</strong> - <b>Condition</b>:   Covid19 Vaccine<br/><b>Interventions</b>:   Biological: MVC-COV1901(S protein with adjuvant);   Biological: MVC-COV1901(Saline)<br/><b>Sponsor</b>:   Medigen Vaccine Biologics Corp.<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>The Safety and Efficacy of Pyronaridine-artesunate (Pyramax® or Artecom®)in COVID-19 Patients</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Artecom® (pyronaridine-artesunate);   Drug: Placebo<br/><b>Sponsor</b>:   Shin Poong Pharmaceutical 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>Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: BGE-175;   Other: Placebo<br/><b>Sponsor</b>:   BioAge Labs, Inc.<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>Safety and Immunogenicity of Two Different Strengths of the Inactivated COVID-19 Vaccine ERUCOV-VAC</strong> - <b>Condition</b>:   COVID-19 Vaccine<br/><b>Interventions</b>:   Biological: ERUCOV-VAC;   Other: Placebo Vaccine<br/><b>Sponsors</b>:   Health Institutes of Turkey;   TC Erciyes 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>Efficacy of Ramdicivir and Baricitinib for the Treatment of Severe COVID 19 Patients</strong> - <b>Conditions</b>:   Covid19;   Covid-19 ARDS<br/><b>Interventions</b>:   Drug: Remdesivir;   Drug: Baricitinib;   Drug: Tocilizumab<br/><b>Sponsors</b>:   M Abdur Rahim Medical College and Hospital;   First affiliated Hospital Xi'an Jiaoting 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>Antiseptic Mouth Rinses to Reduce Salivary Viral Load in COVID-19 Patients</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Betadine© bucal 100 mg/ml;   Drug: Oximen® 3%;   Drug: Clorhexidine Dental PHB©;   Drug: Vitis Xtra Forte©;   Drug: Distilled Water<br/><b>Sponsors</b>:   Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana;   Hospital Universitario Fundación Jiménez Díaz;   Hospital Universitario General de Villalba;   Hospital Universitario Infanta Elena;   Hospital Universitario Virgen de la Arrixaca;   Hospital Clínico Universitario de Valencia;   Dentaid SL<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>The Effect of Deep Breathing Exercise on Dyspnea, Anxiety and Quality of Life in Patients Treated for COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: Deep Breathing Exercise with Triflo<br/><b>Sponsor</b>:   Ankara University<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>RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: C144-LS and C-135-LS<br/><b>Sponsor</b>:   Rockefeller 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>Pilot Study of Cefditoren Pivoxil in COVID-19 Patients With Mild to Moderate Pneumonia</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Drug: Cefditoren pivoxil 400mg<br/><b>Sponsor</b>:   Meiji Pharma Spain S.A.<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>The Influence of Covid-19 on the Audio-vestibular System</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Diagnostic Test: Audio-Vestibular evaluation<br/><b>Sponsor</b>:   HaEmek Medical Center, Israel<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 COVID-19 Outbreak in Hospital Departments of Bamako, Mali</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Diagnostic Test: SARS-CoV-2 screening by molecular biology;   Diagnostic Test: Serological screening<br/><b>Sponsor</b>:   Institut National de la Santé Et de la Recherche Médicale, France<br/><b>Not yet 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>Enfuvirtide, an HIV-1 fusion inhibitor peptide, can act as a potent SARS-CoV-2 fusion inhibitor: an in silico drug repurposing study</strong> - Regarding the urgency of therapeutic measures for coronavirus disease 2019 (COVID-19) pandemic, the use of available drugs with FDA approval is preferred because of the less time and cost required for their development. In silico drug repurposing is an accurate way to speed up the screening of the existing FDA-approved drugs to find a therapeutic option for COVID-19. The similarity in SARS-CoV-2 and HIV-1 fusion mechanism to host cells can be a key point for Inhibit SARS-CoV-2 entry into host...</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-silico analysis of the inhibition of the SARS-CoV-2 main protease by some active compounds from selected African plants</strong> - CONCLUSIONS: In our study, most of the active phytocomponents of the investigated plants exhibited relative inhibitory potentials against Mpro of SARS-CoV-2 and preferred pharmacological features when compared with hydroxychloroquine. These findings indicate these compounds are potentially antiviral candidates against SARS-CoV-2.</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>Combination and tricombination therapy to destabilize the structural integrity of COVID-19 by some bioactive compounds with antiviral drugs: insights from molecular docking study</strong> - Recently, the SARS-CoV-2 (COVID-19) pandemic virus has been spreading throughout the world. Until now, no certified drugs have been discovered to efficiently inhibit the virus. The scientists are struggling to find new safe bioactive inhibitors of this deadly virus. In this study, we aim to find antagonists that may inhibit the activity of the three major viral targets: SARS-CoV-2 3-chymotrypsin-like protease (6LU7), SARS-CoV-2 spike protein (6VYB), and a host target human angiotensin-converting...</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>Statins as inhibitors of voltage-gated potassium channels Kv1.3 in cancer cells</strong> - Voltage-gated potassium channels are integral membrane proteins selectively permeable for potassium ions and activated upon change of membrane potential. Voltage-gated potassium channels of the Kv1.3 type were discovered both in plasma membrane and in inner mitochondrial membrane (mito Kv1.3 channels). For some time Kv1.3 channels located both in plasma membrane and in mitochondria are considered as a potentially new molecular target in several pathologies including some cancer disorders....</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>Antiviral activity of lambda-carrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2</strong> - Influenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses with EC(50) values ranging from 0.3 to 1.4 μg/ml, as well as currently circulating...</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>Mechanism of SARS-CoV-2 polymerase stalling by remdesivir</strong> - Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism 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>Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein</strong> - CONCLUSIONS: In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2.</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 network-based model to explore the role of testing in the epidemiological control of the COVID-19 pandemic</strong> - CONCLUSIONS: Although testing could effectively inhibit the spread of infectious diseases and epidemics, our results indicated that it requires a huge daily testing volume. Thus, it is highly recommended that testing be adopted in combination with measures such as wearing masks and social distancing to better manage infectious diseases. Our research contributes to understanding the role of testing in epidemic control and provides useful suggestions for the government and individuals in...</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>Biological characteristics and biomarkers of novel SARS-CoV-2 facilitated rapid development and implementation of diagnostic tools and surveillance measures</strong> - Existing coronavirus named as a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has speeded its spread across the globe immediately after emergence in China, Wuhan region, at the end of the year 2019. Different techniques, including genome sequencing, structural feature classification by electron microscopy, and chest imaging using computed tomography, are primarily used to diagnose and screen SARS-CoV-2 suspected individuals. Determination of the viral structure, surface proteins,...</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>Evaluation of certain medicinal plants compounds as new potential inhibitors of novel corona virus (COVID-19) using molecular docking analysis</strong> - SARS-CoV-2 is a new strain of coronavirus that appeared in China in December 2019, in recent years, great progress has been made in developing new antiviral drugs, and natural products, are important sources of potential and new antiviral drugs. The present study aimed to assess some biologically active compounds present in medicinal plants as potential COVID-19 inhibitors, using molecular docking methods. The Docking study was performed by Molecular Operating Environment software (MOE). About...</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>Proposed Mechanisms of Targeting COVID-19 by Delivering Mesenchymal Stem Cells and Their Exosomes to Damaged Organs</strong> - With the outbreak of coronavirus disease (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world has been facing an unprecedented challenge. Considering the lack of appropriate therapy for COVID-19, it is crucial to develop effective treatments instead of supportive approaches. Mesenchymal stem cells (MSCs) as multipotent stromal cells have been shown to possess treating potency through inhibiting or modulating the pathological events in COVID-19. MSCs...</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>Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations</strong> - Structure-activity relationships for hydroxychloroquine compound and its derivatives resulted in a potent antiviral activity. Where hydroxychloroquine derivatives showed an apparent efficacy against coronavirus related pneumonia. For this reason, the current study is focused on the structural properties of hydroxychloroquine and hydroxychloroquine sulfate. Optimized structures of these molecules have been reported by using DFT method at B3LYP/6-31G* level of theory. Te geometric were determined...</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 trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent</strong> - Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based...</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>Upregulation of DUSP6 impairs infectious bronchitis virus replication by negatively regulating ERK pathway and promoting apoptosis</strong> - Elucidating virus-cell interactions is fundamental to understanding viral replication and identifying targets for therapeutic control of viral infection. The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate pathogenesis during many viral infections, but its role during coronavirus infection is undetermined. Infectious bronchitis virus is the representative strain of Gammacoronavirus, which causes acute and highly contagious diseases in the poultry farm. In this...</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>Repurposing existing drugs: identification of SARS-CoV-2 3C-like protease inhibitors</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Since its emergence, the COVID-19 pandemic has not only distressed medical services but also caused economic upheavals, marking urgent the need for effective therapeutics. The experience of combating SARS-CoV and MERS-CoV has shown that inhibiting the 3-chymotrypsin-like protease (3CLpro) blocks the replication of the virus. Given the well-studied properties of FDA-approved drugs,...</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU314054415">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313300659">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid 19 - Chewing Gum</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313269181">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19</strong> - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN313339294">link</a></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fahrzeuglüftungssystem und Verfahren zum Betreiben eines solchen Fahrzeuglüftungssystems</strong> -
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.</p></li>
</ul>
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<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE313868337">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251184">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251182">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>"AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2."</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN312324209">link</a></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mund-Nasen-Bedeckung</strong> -
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Mund-Nasen-Bedeckung (1), wobei die Mund-Nasen-Bedeckung (1) mindestens an einem Ohr eines Trägers magnetisch befestigbar ist.</p></li>
</ul>
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<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE313866760">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU311608060">link</a></p></li>
</ul>
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