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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>Misinformation about Covid-19 Vaccines on Social Media: Rapid Review</strong> -
<div>
The development of COVID-19 vaccines has been crucial in fighting the pandemic. Misinformation about COVID-19 vaccines on social media is a major challenge, as this is thought to contribute to vaccine hesitancy. Here, we review the research on misinformation about COVID-19 vaccines spread on social media platforms. The review is registered with the PROSPERO international register of systematic reviews (CRD42021277524). We performed a literature search on 9 September 2021 and searched PubMed, PsycINFO, ERIC, Embase, Cochrane Library, and the Cochrane COVID-19 Study Register. We included publications in peer-reviewed journals that fulfilled all following criteria: Original empirical studies, studies that assessed social media and misinformation, studies that dealt with vaccine hesitancy, and studies about the COVID-19 vaccine. Publications were excluded if data were gathered before Phase III in the first COVID-19 vaccine development (from July 27 2020 to November 13, 2020). The narrative qualitative synthesis was undertaken with the guidance of the PRISMA 2020 Statement and the Synthesis Without Meta-analysis reporting guideline. The risk of bias was assessed according to The Joanna Briggs Institute (JBI) Critical Appraisal tool. Ratings of the certainty of evidence were based on recommendations from the GRADE Working Group. The search amounted to 757 records, with 45 articles selected for the review. There are many types of misinformation that are spread on social media platforms. We identified three main areas of misinformation: Medical misinformation, vaccine development, and conspiracies. To prevent these misconceptions from taking hold, health authorities should openly address and discuss these false claims with both cultural and religious awareness in mind. Our review showed that there is a need to examine the effect of social media misinformation on vaccine hesitancy with a more robust experimental design. Furthermore, our review also demonstrated that more studies are needed from the Global South and on other social media platforms than the major platforms such as Twitter.
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🖺 Full Text HTML: <a href="https://osf.io/tyevj/" target="_blank">Misinformation about Covid-19 Vaccines on Social Media: Rapid Review</a>
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<li><strong>Effects of 12 weeks of Multi-nutrient supplementation on the Immune and Musculoskeletal systems of Older Adults in Aged-Care (The Pomerium Study): Protocol for a Randomised Controlled Trial</strong> -
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Introduction: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with Sars-Cov2, which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intake associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the effects of inadequate nutrition can be reversed by multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections, and improving respiratory and muscle function. Methods and analysis: The Pomerium Study is a 12-week, single-blinded, randomised, placebo-controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20g protein, 1.2g CaHMB, 449mg calcium, 520IU vitamin D3, and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged-care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged-care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). Primary outcome is the change in T-cell subsets CD8+ and CD28null counts at 4 and 12 weeks post-intervention. Secondary outcomes measured at baseline and after 12 weeks post-intervention are multiple markers of immunosenescence, body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry), and quality of life (EQ-5D-3L). Incidence and complications of COVID-19 and/or viral infections (i.e., hospitalisation, complications, or death) will be recorded throughout the trial. Discussion: If the Pomerium Study demonstrates efficacy and safety of a multi-nutrient supplement on immune, muscle and respiratory function, it may be suitable as a strategy to reduce the adverse outcomes from seasonal influenza and viral infections such as COVID-19 in older adults in aged-care.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.23.22269669v1" target="_blank">Effects of 12 weeks of Multi-nutrient supplementation on the Immune and Musculoskeletal systems of Older Adults in Aged-Care (The Pomerium Study): Protocol for a Randomised Controlled Trial</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Border closure and travel restrictions to control the spread of COVID-19: an update to a Cochrane review</strong> -
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Background: COVID-19 has proven to be more difficult to manage for many reasons including its high infectivity rate. One of the potential ways to limit its spread is by limiting free travel across borders, including via air travel. The objective of this systematic review is to identify, critically-appraise and summarize evidence on border closures and travel restrictions. Methods: This review is based on the Cochrane review: “International travel-related control measures to contain the COVID-19 pandemic” and followed the same methodology. In brief, we searched for clinical and modelling studies in general health and COVID-19-specific bibliographic databases. The primary outcome categories were</p></div></li>
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<li>cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. Results: We included 55, mostly modelling, studies that met our inclusion criteria. Fourteen new studies were identified in the updated search, as well as updated companions (e.g., peer-reviewed publications that were previously only available as pre-prints). Most studies were of moderate to high quality. The added studies did not change the main conclusions of the Cochrane review nor the quality of the evidence (very low to low certainty). However, it did add to the evidence base for most outcomes. Conclusions: Weak evidence supports the use of border closures to limit the spread of COVID-19 from region to regions via air travel. Real-world studies are required to support these conclusions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.22.22269686v1" target="_blank">Border closure and travel restrictions to control the spread of COVID-19: an update to a Cochrane review</a>
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<li><strong>The Epidemiology of Hundreds of Individuals Infected with Omicron BA.1 in Middle-Eastern Jordan</strong> -
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One month after its detection in Jordan, B.1.1.529 is constituting about 60% of all confirmed COVID-19 infections causing a rise in the daily cases in the country. Herein, we report on 500 omicron-infected cases to get a better understanding of this variant and its behavior in different geographies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.23.22269442v1" target="_blank">The Epidemiology of Hundreds of Individuals Infected with Omicron BA.1 in Middle-Eastern Jordan</a>
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<li><strong>A qualitative process analysis of DCT as an alternative to self-isolation following close contact with a confirmed case of COVID-19</strong> -
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Background In July 2021, a randomised controlled trial was conducted to compare the effect on SARS-CoV-2 transmission of seven days of daily contact testing (DCT) using lateral flow devise (LFT) and 2 PCR tests as an alternative to 10 days of standard self-isolation with 1 PCR, following close contact with a confirmed case of COVID-19. DCT appeared equivalent to self-isolation in terms of transmission in the trial, however it was not clear how tests were viewed and used in practice. In this qualitative study, we used a nested process to aid interpretation of the trial and provide insight into factors influencing use of tests, understanding of test results, and how tests were used to inform behavioural decisions. Methods Interviews were conducted with 60 participants (42 randomised to DCT and 18 randomised to self-isolation) who had been in close contact with a confirmed positive case of COVID-19 and had consented to take part in the trial. Results Sub-themes emerging from the data were organised into three overarching themes: (1) assessing the risks and benefits of DCT; (2) use of testing during the study period and (3) future use of testing. Attitudes toward DCT as an alternative to self-isolation, and behaviour during the testing period appeared to be informed by an assessment of the associated risks and benefits. Participants reported how important it was for them to avoid isolation, how necessary self-isolation was considered to be, and the ability of LFTs to detect infection. Behaviour during the testing period was modified to reduce risks and harms as much as possible. Testing was considered a potential compromise, reducing both risk of transmission and the negative impact of self-isolation and was highly regarded as a way to 9return to new normal9. Conclusion Participants in this study viewed DCT as a sensible, feasible and welcome means of avoiding unnecessary self-isolation. Although negative LFTs provided reassurance, most people still restricted their activity as recommended. DCT was also highly valued by those in vulnerable households as a means of providing reassurance of the absence of infection, and as an important means of detecting infection and prompting self- isolation when necessary.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.14.21267257v1" target="_blank">A qualitative process analysis of DCT as an alternative to self-isolation following close contact with a confirmed case of COVID-19</a>
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<li><strong>Learnings from the Australian First Few X Household Transmission Project for COVID-19</strong> -
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Background: First Few “X” (FFX) studies provide a platform to collect the required epidemiological, clinical and virological data to help address emerging information needs about the COVID-19 pandemic. Methods: We adapted the WHO FFX protocol for COVID-19 to understand severity and household transmission dynamics in the early stages of the pandemic in Australia. Implementation strategies were developed for participating sites; all household members provided baseline epidemiological data and were followed for 14 days from case identification. Household contacts completed symptom diaries and had respiratory swabs taken at baseline, day 7 and day 14, and day 28 where applicable. We modelled the spread of COVID-19 within households using a susceptible-exposed-infectious-recovered-type model, and calculated the household secondary attack rate and key epidemiological parameters. Findings: 96 households with 101 cases and 286 household contacts were recruited into the study between AprilOctober 2020. Forty household contacts tested positive for SARS-CoV-2 in the study follow-up period. Our model estimated the household secondary attack rate to be 15% (95% CI 825%), which scaled up with increasing household size. Children were less infectious than their adult counterparts but were also more susceptible to infection. Interpretation: Our study provides important baseline data characterising the transmission of early SARS-CoV-2 strains from children and adults in Australia, against which properties of variants of concern can be benchmarked. We encountered many challenges with respect to logistics, ethics, governance and data management that may have led to biases in our study. Continued efforts to invest in preparedness research will help to test, refine and further develop Australian FFX study protocols in advance of future outbreaks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.23.22269031v1" target="_blank">Learnings from the Australian First Few X Household Transmission Project for COVID-19</a>
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<li><strong>Over- and under-estimation of vaccine effectiveness</strong> -
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SARS-CoV-2 vaccines provide not just high protection against infection to the vaccinated individual but also provide indirect protection to its surroundings by blocking further transmission. Divergent results have been reported on the effectiveness of the SARS-CoV-2 vaccines. Here, we argue that this divergence is due to the fact that the analyses did not take into account the indirect protection. Using a novel heterogeneous infection model and real-world data, we demonstrate that heterogeneous vaccination rates among families and communities, and the study design that is used, may significantly skew the vaccine effectiveness estimations. We show that estimations of a vaccine with 85% effectiveness will vary between marked underestimation of 70% and overestimation of 95% depending on the number of interactions between vaccinated and unvaccinated individuals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.24.22269737v1" target="_blank">Over- and under- estimation of vaccine effectiveness</a>
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<li><strong>T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components</strong> -
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SARS-CoV-2 provokes a brisk T cell response. Peptide-based studies exclude antigen processing and presentation biology and may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DC to activate CD8 and CD4 T cells from convalescent persons. T cell receptor (TCR) sequencing showed partial repertoire preservation after expansion. Resultant CD8 T cells recognize SARS- CoV-2-infected respiratory cells, and CD4 T cells detect inactivated whole viral antigen. Specificity scans with proteome-covering protein/peptide arrays show that CD8 T cells are oligospecific per subject and that CD4 T cell breadth is higher. Some CD4 T cell lines enriched using SARS-CoV-2 cross-recognize whole seasonal coronavirus (sCoV) antigens, with protein, peptide, and HLA restriction validation. Conversely, recognition of some epitopes is eliminated for SARS- CoV-2 variants, including spike (S) epitopes in the alpha, beta, gamma, and delta variant lineages.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.23.22269497v1" target="_blank">T cell response to intact SARS- CoV-2 includes coronavirus cross-reactive and variant-specific components</a>
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<li><strong>BASELINE METABOLIC PROFILING AND RISK OF DEATH FROM COVID-19</strong> -
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Objective: To derive a predicted probability of death (PDeathLabs) based upon complete value sets for 11 clinical measurements (CM) obtained on patients prior to their diagnosis of COVID-19. PDeathLabs is intended for use as a summary metric for baseline metabolic status in multivariate models for COVID-19 death. Methods: Cases were identified through the COVID-19 Shared Data Resource (CSDR) of the Department of Veterans Affairs. The diagnosis required at least one positive nucleic acid amplification test (NAAT). The primary outcome was death within 60 days of the first positive test. We retrieved all values for systolic blood pressure (SBP), diastolic blood pressure (DBP), O2 saturation (O2SAT), body mass index (BMI), estimated glomerular filtration rate (EGFR), alanine aminotransferase (ALT), serum albumin (ALB), hematocrit (HCT), LDL cholesterol (LDL) hemoglobin A1c (A1C), and HDL cholesterol (HDL) if they were done at least 14 days prior to the NAAT. Clinicians evaluate several attributes of CM that are of critical importance: metabolic control, disease burden, chronicity, refractoriness, tendency to relapse, temporal trends, and lability. We derived 1-3 parameters for each of these attributes: the most recent value (metabolic control); time-weighted average and abnormal area under a severity versus time curve (disease burden); time and number of readings above or below goal (chronicity); longest abnormal cluster and time/number of consecutive readings above goal if the last value was abnormal (refractoriness); number of abnormal clusters (tendency to relapse); long- and short-term changes (temporal trends); and coefficient of variation and mean deviation between consecutive readings (lability). We created computer programs to derive cumulative values for these 13 parameters for all 11 CM as each new value is added. A fitted logistic model was developed for each CM to determine which of the 13 parameters contributed to the risk of death. A main logistic model was developed to determine which of the 13 * 11 = 143 metabolic parameters were independently predictive of death. The resulting model was used to derive PDeathLabs for each patient and the area under its receiver operating characteristic (ROC) curve calculated. Single variable logistic models were also derived for age at diagnosis, the Charlson 2-year (Charl2Yr) and lifetime (CharlEver) scores, and the Elixhauser 2-year (Elix2Yrs) and lifetime (ElixEver) scores. Stata was used to compare the ROCs for PDeathDx and each of the other metrics. Results: On September 30, 2021 there were 347,220 COVID-19 patients in the CSDR. 329,491 (94.9%) patients had CM performed at least 14 days prior to the COVID-19 diagnosis and form the basis for this report. 17,934 (5.44%) died within 60 days of the diagnosis. On the subset regressions, the number of significant parameters ranged from all 13 for SBP to 7 for HDL. 239,393 patients had complete sets of data for developing the main model. Of 143 candidate predictors, 49 parameters were identified as statistically significant, independent predictors of death. The most influential domains were the most recent value, disease burden, temporal trends, and tendency to relapse. The ROC area for PDeathLabs was 0.785 +/- 0.002. No difference was found in the ROC areas of PDeathLabs and age at diagnosis (0.783 +/- 0.002; P = NS). However, the ROC area for PDeathLabs was significantly greater than that of Charl2Yrs (0.704 +/- 0.002; P &lt; 0.001), CharlEver (0.729 +/- 0.002; P &lt; 0.001), Elix2Yrs (0.675 +/- 0.002; P &lt; 0.001), and ElixEver (0.707 +/- 0.002; P &lt; 0.001). A poor prognosis was found for chronic systolic hypertension. On the other hand, a higher BMI was protective once SBP, DBP, HDL, LDL and A1C were considered. Conclusions: Our study confirms that parameters derived for 11 CM are significant determinants of COVID-19 death. The most recent value should not be selected over other parameters for multivariate modeling unless there is a physiologic basis for doing so. PDeathLabs has the same discriminating power as age at d
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.22.22269691v1" target="_blank">BASELINE METABOLIC PROFILING AND RISK OF DEATH FROM COVID-19</a>
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<li><strong>Nasally-delivered interferon-{lambda} protects mice against upper and lower respiratory tract infection of SARS- CoV-2 variants including Omicron</strong> -
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Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with SARS-CoV-2 infection, variants with constellations of mutations in the spike gene threaten their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine IFN-{lambda} has been proposed as a possible treatment based on correlative studies in human COVID-19 patients. Here, we show IFN-{lambda} protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron) variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally-delivered IFN-{lambda}2 limited infection of historical or variant (B.1.351 and B.1.1.529) SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-{lambda} was produced preferentially in epithelial cells and acted on radio-resistant cells to protect against of SARS-CoV-2 infection. Thus, inhaled IFN-{lambda} may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.21.477296v1" target="_blank">Nasally-delivered interferon-{lambda} protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron</a>
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<li><strong>The N764K and N856K mutations in SARS-CoV-2 Omicron S protein generate potential cleavage sites for SKI-1/S1P protease</strong> -
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Spike (S) protein is a key protein in coronaviruses life cycle. SARS-CoV-2 Omicron variant of concern (VoC) presents an exceptionally high number of 30 substitutions, 6 deletions and 3 insertions in the S protein. Recent works revealed major changes in the SARS-CoV-2 Omicron biological properties compared to earlier variants of concern (VoCs). Here, these major changes could be explained, at least in part, by the mutations N764K and/or N856K in S2 subunit. These mutations were not previously detected in other VoCs. N764K and N856K generate two potential cleavage sites for SKI-1/S1P serine protease, known to cleave viral envelope glycoproteins. The new sites where SKI-1/S1P could cleave S protein might impede the exposition of the internal fusion peptide for membrane fusion and syncytia formation. Based on the human protein atlas, SKI-1/S1P protease is not found in lung tissues (alveolar cells type I/II and endothelial cells), but present in bronchus and nasopharynx. This may explain why Omicron has change of tissue tropism. Viruses have evolved to use several host proteases for cleavage/activation of envelope glycoproteins. Mutations that allow viruses to change of protease may have a strong impact in host range, cell and tissue tropism, and pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.21.477298v1" target="_blank">The N764K and N856K mutations in SARS-CoV-2 Omicron S protein generate potential cleavage sites for SKI-1/S1P protease</a>
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<li><strong>SARS-CoV-2 Omicron variant virus isolates are highly sensitive to interferon treatment</strong> -
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Recently, we have shown that SARS-CoV-2 Omicron virus isolates are less effective at inhibiting the host cell interferon response than Delta viruses. Here, we present further evidence that reduced interferon-antagonising activity explains at least in part why Omicron variant infections are inherently less severe than infections with other SARS- CoV-2 variants. Most importantly, we here also show that Omicron variant viruses display enhanced sensitivity to interferon treatment, which makes interferons promising therapy candidates for Omicron patients, in particular in combination with other antiviral agents.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.20.477067v1" target="_blank">SARS-CoV-2 Omicron variant virus isolates are highly sensitive to interferon treatment</a>
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<li><strong>Bacteriophage-derived dsRNA exerts anti-SARS-CoV-2 activity in vitro and in Golden Syrian hamsters in vivo</strong> -
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Purpose: Bacteriophage-derived dsRNA, also known as Larifan, is nationally well-known broad-spectrum antiviral medication. The goal of this study was to ascertain the antiviral activity of Larifan against the novel SARS-CoV-2. Methods: The antiviral activity of Larifan against SARS-CoV-2 in vitro was measured in human lung adenocarcinoma (Calu3) and primary human small airway epithelial cells (HSAEC) using cytopathic effect assay, viral RNA copy number detection by digital droplet PCR (ddPCR) and infectious virus titration in cells supernatants in Vero E6 cells by end-point titration method. The antiviral effect of Larifan in vivo was detected in SARS-CoV-2 infection model in Golden Syrian hamsters. Larifan (5 mg/kg) was administered either subcutaneously or intranasally twice before and after virus infection with a 24-hour interval between doses. The viral RNA copies and infectious virus titre were detected in animal lungs at day three and five post-infection using ddPCR and end-point titration in Vero E6 cells, respectively. Histopathology of lungs was analysed as well. Results: Larifan inhibited SARS-CoV-2 replication in Calu3 cells both after the drug addition pre- and pot-infection with a substantial drop in the supernatant viral RNA copy numbers from eight (p = 0.0013) to twenty (p = 0.0042) times, respectively. Similarly, infectious virus titre in Vero E6 cells dropped by 3.6log10 and 2.8log10 after the drug addition pre- and pot-infection, respectively. In HSAEC, Larifan inhibited SARS-CoV-2 replication at the similar level. Larifan also markedly reduced virus numbers in the lungs of infected hamsters (p = 0.0032) both at day three and five post-infection with a more pronounced effect after intranasal administration reaching a drop by 2.7log10 at day three and 2.0log10 at day five. The administration of Larifan also reduced the amount of infections virus titer in lungs (p = 0.0039) by 4.3log10 and 2.8log10 at day three and five post-infection, respectively. Improvements in the infection-induced pathological lesion severity in the lungs of animals treated with Larifan were also demonstrated by histological analyses. Conclusions: The inhibition of SARS-CoV-2 replication in vitro and the reduction of the viral load in the lungs of infected hamsters treated with Larifan alongside the improved lung histopathology, suggests a potential use of Larifan in controlling the COVID-19 disease in humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.22.477073v1" target="_blank">Bacteriophage-derived dsRNA exerts anti-SARS-CoV-2 activity in vitro and in Golden Syrian hamsters in vivo</a>
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<li><strong>Lack of Ronapreve (REGN-CoV; casirivimab and imdevimab) virological efficacy against the SARS-CoV 2 Omicron variant (B.1.1.529) in K18-hACE2 mice</strong> -
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The Omicron variant (B.1.1.529) of SARS-CoV-2 has placed enormous strain on global healthcare systems since it was first identified by South African researchers in late 2021. Omicron has &gt;50 mutations which mainly occur in the surface spike protein and this has led to rapid assessment of monoclonal antibodies to assess the impact on virus neutralisation. Ronapreve has shown potential application in post-exposure prophylaxis, mild/moderate disease and in seronegative patients with severe COVID19, but several early reports of loss of in vitro neutralisation activity have been documented. Here, the virological efficacy of Ronapreve was assessed in K18-hACE2 mice to provide an in vivo outcome. Ronapreve reduced sub-genomic RNA in lung and nasal turbinate for the Delta variant but not the Omicron variant of SARS-CoV-2 at doses 2-fold higher than those shown to be active against previous variants of the virus. These data add to the growing evidence that the effectiveness of Ronapreve is compromised for the Omicron variant.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.23.477397v1" target="_blank">Lack of Ronapreve (REGN-CoV; casirivimab and imdevimab) virological efficacy against the SARS-CoV 2 Omicron variant (B.1.1.529) in K18-hACE2 mice</a>
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<li><strong>Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19</strong> -
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COVID 19 is the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; SC2) which has caused a world-wide pandemic with striking morbidity and mortality. Evaluation of early SC2 strains suggested limited viral genetic diversity. However, genetic and epidemiologic investigations in the interim have revealed impressive genetic variability. Many of these viral variants are now defined as variants of concern (VOC) based on genetic alterations in their spike (S) and other proteins that cause enhanced transmissibility, decreased susceptibility to antibody neutralization or therapeutics and or their ability to induce severe disease. The delta {delta} and omicron (o) variants are particularly problematic based on their impressive and unprecedented transmissibility and ability to cause break through infections. The delta variant also accumulates at high concentrations in host tissues and has caused waves of lethal disease. SC2 infection is mediated by S protein binding to cellular ACE2 receptors and subsequent S protein protease processing. Because studies from our laboratory have demonstrated that chitinase 3-like-1 (CHI3L1) stimulates ACE2 and S priming proteases, studies were undertaken to determine if interventions that target CHI3L1 are effective inhibitors of SC2 viral variant infection. Here we demonstrate that CHI3L1 augments epithelial cell infection by pseudoviruses that express the alpha, beta, gamma, delta or omicron S proteins and that the CHI3L1 inhibitors anti- CHI3L1 and kasugamycin inhibit epithelial cell infection by these VOC pseudovirus moieties. Thus, CHI3L1 is a universal, VOC-independent therapeutic target in COVID 19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.21.477274v1" target="_blank">Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Quantifying Viral Load in Respiratory Particles That Are Generated by Children and Adults With COVID-19 Infection</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Device: COVID-19 Aerosol Collection<br/><b>Sponsor</b>:  <br/>
Massachusetts General Hospital<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>Evaluation of Safety &amp; Efficacy of MIR 19 ® Inhalation Solution in Patients With Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: MIR 19 ®;   Combination Product: Standard COVID-19 therapy<br/><b>Sponsors</b>:   National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia;   St. Petersburg Research Institute of Vaccines and Sera<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>A Study to Evaluate the Safety and Immunogenicity of Booster With AZD1222, mRNA-1273, or MVC-COV1901 Against COVID-19</strong> - <b>Condition</b>:   COVID-19 Vaccine<br/><b>Interventions</b>:   Biological: Half dose of MVC-COV1901;   Biological: Full dose of MVC-COV1901;   Biological: AZD1222;   Biological: Half dose of mRNA-1273<br/><b>Sponsors</b>:   Medigen Vaccine Biologics Corp.;   Coalition for Epidemic Preparedness Innovations<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>Efficacy of Breathox Device Inhalation Therapy in the Treatment of Acute Symptoms Associated With COVID-19 and in the Prevention of the Use of Health Resources</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: BREATHOX 5 sessions;   Drug: BREATHOX 10 sessions<br/><b>Sponsors</b>:   UPECLIN HC FM Botucatu Unesp;   Liita Holdings LTD<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>Randomized Multicenter Study on the Efficacy and Safety of Favipiravir for Parenteral Administration Compared to Standard of Care in Hospitalized Patients With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Favipiravir;   Drug: Remdesivir<br/><b>Sponsors</b>:   Promomed, LLC;   Solyur Pharmaceuticals Group<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>Immunogenicity of an Inactivated COVID-19 Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Inactivated COVID-19 Vaccine<br/><b>Sponsor</b>:   Sinovac Research and Development Co., Ltd.<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>Inhaled Heparin for Hospitalised Patients With Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: unfractionated Heparin<br/><b>Sponsors</b>:  <br/>
Australian National University;   The George Institute;   St George Hospital, Australia;   St Vincents Hospital Melbourne;   John Hunter Hospital;   Royal North Shore Hospital<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 Prospective, Phase II Study to Evaluate Safety of 101-PGC-005 (005) for Moderate to Severe COVID-19 Disease Along With Standard of Care</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: 101-PGC-005 (005) + SOC;   Drug: Placebo + SOC<br/><b>Sponsor</b>:   101 Therapeutics<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>Intranasal Heparin Treatment to Reduce Transmission Among Household Contacts of COVID 19 Positive Adults and Children</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: unfractionated heparin;   Drug: 0.9%sodium chloride<br/><b>Sponsors</b>:   Murdoch Childrens Research Institute;   University of Melbourne;   Northern Hospital, Australia;   Monash University;   The Peter Doherty Institute for Infection and Immunity;   St Vincents Hospital Melbourne<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>Immunogenicity and Safety Study of a SCB-2019 Vaccine Booster Dose to Adults Who Previously Received Primary Series of Selected COVID-19 Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Candidate vaccine, SCB-2019<br/><b>Sponsor</b>:   Clover Biopharmaceuticals AUS Pty 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>Increasing COVID-19 Testing in Chicagos African American Testing Desserts</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Intervention</b>:   Behavioral: COVID-19 Testing<br/><b>Sponsor</b>:   Rush University Medical Center<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>Heterologous Boost Immunization With an Aerosolised Ad5-nCoV After Two-dose Priming With an Inactivated SARS-CoV-2 Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Aerosolized Ad5-nCoV;   Biological: Inactivated SARS-CoV-2 vaccine<br/><b>Sponsor</b>:   Jiangsu Province Centers for Disease Control and Prevention<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>IMPACT OF THERAPEUTIC PLASMA EXCHANGE ON ACQUIRED VACCINAL ANTI-SARS-CoV-2 ANTIBODIES.</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Diagnostic Test: Evolution of antibodies titre<br/><b>Sponsor</b>:   Cliniques universitaires Saint-Luc- Université Catholique de Louvain<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>Respiratory Physiotherapy and Neurorehabilitation in Patients With Post-covid19 Sequelae.</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Intervention</b>:   Other: respiratory treatment<br/><b>Sponsor</b>:   Universidad Católica de Ávila<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>The Effect of Telemonitoring on Anxiety and Quality of Life in Patients in COVID 19 Quarantine</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Intervention</b>:   Other: tele-monitoring<br/><b>Sponsor</b>:  <br/>
Yuksek Ihtisas University<br/><b>Completed</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>Anti-inflammatory and anti-COVID-19 effect of a novel polyherbal formulation (Imusil) via modulating oxidative stress, inflammatory mediators and cytokine storm</strong> - In the current scenario, most countries are affected by COVID-19, a pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has a massive impact on human health. Previous studies showed that some traditionally used medicinal herbs and their combinations showed synergistic anti-viral and anti-inflammatory activity against SARS-CoV-2 type infections. Therefore, the goal of this study is to demonstrate the anti-viral and anti- inflammatory effects of a novel…</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>Dynamical demeanour of SARS-CoV-2 virus undergoing immune response mechanism in COVID-19 pandemic</strong> - COVID-19 is caused by the increase of SARS-CoV-2 viral load in the respiratory system. Epithelial cells in the human lower respiratory tract are the major target area of the SARS-CoV-2 viruses. To fight against the SARS-CoV-2 viral infection, innate and thereafter adaptive immune responses be activated which are stimulated by the infected epithelial cells. Strong immune response against the COVID-19 infection can lead to longer recovery time and less severe secondary complications. We proposed a…</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>Vaccine booster efficiently inhibits entry of SARS-CoV-2 omicron variant</strong> - No abstract</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 structure of a novel antibody against the spike protein inhibits Middle East respiratory syndrome coronavirus infections</strong> - Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus, responsible for outbreaks of a severe respiratory illness in humans with a fatality rate of 30%. Currently, there are no vaccines or United States food and drug administration (FDA)-approved therapeutics for humans. The spike protein displayed on the surface of MERS-CoV functions in the attachment and fusion of virions to host cellular membranes and is the target of the host antibody response. Here, we provide a…</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>SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules</strong> - As a highly pathogenic human coronavirus, SARS-CoV-2 has to counteract an intricate network of antiviral host responses to establish infection and spread. The nucleic acid-induced stress response is an essential component of antiviral defense and is closely related to antiviral innate immunity. However, whether SARS-CoV-2 regulates the stress response pathway to achieve immune evasion remains elusive. In this study, SARS-CoV-2 NSP5 and N protein were found to attenuate antiviral stress granule…</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>Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Coronavirus Infection</strong> - BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti- coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG…</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>Thiol-based chemical probes exhibit antiviral activity against SARS-CoV-2 via allosteric disulfide disruption in the spike glycoprotein</strong> - The development of small-molecules targeting different components of SARS-CoV-2 is a key strategy to complement antibody-based treatments and vaccination campaigns in managing the COVID-19 pandemic. Here, we show that two thiol- based chemical probes that act as reducing agents, P2119 and P2165, inhibit infection by human coronaviruses, including SARS-CoV-2, and decrease the binding of spike glycoprotein to its receptor, the angiotensin-converting enzyme 2 (ACE2). Proteomics and reactive cysteine…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19)</strong> - Since 2019, COVID-19 has become the most important health dilemma around the world. The dysregulated immune response which results in ARDS and cytokine storm has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through induction of pro-inflammatory chemokines and cytokines, is the pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, IL-6 pathway blockade is considered an emerging approach with high efficacy to reduce lung…</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>Immunoediting in SARS-CoV-2: Mutual relationship between the virus and the host</strong> - Immunoediting is a well-known concept that occurs in cancer through three steps of elimination, equilibrium, and escape (3Es), where the immune system first suppresses the growth of tumor cells and then promotes them towards the malignancy. This phenomenon has been conceptualized in some chronic viral infections such as HTLV-1 and HIV by obtaining the resistance to elimination and making a persistent form of infected cells especially in untreated patients. Coronavirus disease 2019 (COVID-19),…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern</strong> - Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture…</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>Potent Inhibitory Activities of the Adenosine Analogue Cordycepin on SARS-CoV-2 Replication</strong> - Nucleoside analogues are among the most successful bioactive classes of druglike compounds in pharmaceutical chemistry as they are well-known for their numerous effective bioactivities in humans, especially as antiviral and anticancer agents. Coronavirus disease 2019 (COVID-19) is still untreatable, with its causing virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continuing to wreak havoc on the ground everywhere. This complicated international situation urged all…</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>RNAi-mediated siRNA sequences to combat the COVID-19 pandemic with the inhibition of SARS-CoV2</strong> - The outbreak of the COVID-19 pandemic has cost five million lives to date, and was caused by a positive-sense RNA virus named SARS-CoV2. The lack of drugs specific to SARS-CoV2, leads us to search for an effective and specific therapeutic approach. Small interfering RNA (siRNA) is able to activate the RNA interference (RNAi) pathway to silence the specific targeted gene and inhibit the viral replication, and it has not yet attracted enough attention as a SARS-CoV2 antiviral agent. It could be a…</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>Online learning in nursing students: Satisfaction and barriers</strong> - CONCLUSIONS: The study data indicated that maximum students were extremely satisfied the with online learning and among barriers which effect online learning is low voice and language clarity, reliability and connectivity problem, physical health barriers such as eye strain.</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>SARS-CoV-2 Causes Mitochondrial Dysfunction and Mitophagy Impairment</strong> - Mitochondria, which is essential for adequate innate immune response, energy metabolism and mitochondria reactive oxygen species (ROS) production, might be in the cross fire of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host cell defense. However, little is known about interactions between mitochondria and SARS-CoV-2. We performed fluorescent microscopy and found an enrichment of SARS-CoV-2 replication products double stranded RNA (dsRNA) within mitochondria. The entry…</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>Possibility as role of ginseng and ginsenosides on inhibiting the heart disease of COVID-19: A systematic review</strong> - Coronavirus has been spreading rapidly around the world since it broke out in China in 2019. Respiratory diseases caused by coronavirus infection cause various diseases ranging from asymptomatic subclinical infections to severe pneumonia and cardiovascular complications, leading to death. In this regard, natural products are being studied to prevent various diseases caused by COVID-19. In current review, we would like to present mechanisms related to the inhibition of heart disease in ginseng…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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