185 lines
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185 lines
54 KiB
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Optimism, Mindfulness, and Resilience as Potential Protective Factors for the Mental Health Consequences of Fear of the Coronavirus</strong> -
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<div>
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The COVID-19 pandemic has a substantial impact on mental health. Prior reports have shown that depression, anxiety, and stress have increased throughout the pandemic. Nonetheless, not everyone is affected by these negative consequences and some people may be relatively unaffected. In this online study in a predominantly Dutch and Belgian sample (N = 546), we investigated whether positive personality traits such as optimism, mindfulness, and resilience may protect against the negative mental health consequences (i.e., fear of the coronavirus, depression, stress, and anxiety) of the COVID-19 pandemic. We found that fear of COVID-19 was related to higher depression, stress, and anxiety. However, for participants scoring high on mindfulness, optimism, and resilience, this relationship was weakened. In addition to these findings, we present the results of network analyses to explore the network structure between these constructs. These results help to identify individuals whose mental health is affected by the COVID-19 pandemic.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/eqx4y/" target="_blank">Optimism, Mindfulness, and Resilience as Potential Protective Factors for the Mental Health Consequences of Fear of the Coronavirus</a>
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<li><strong>Parenting in a Pandemic: Parental Stress During the Physical Distancing Intervention Following the onset of the COVID-19 Outbreak</strong> -
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Objective: The main aim of the study was to examine levels of parental stress and symptoms of depression and anxiety in the general parental population (N = 2868) during the strict government-initiated physical distancing protocols following the onset of the COVID-19 pandemic. We further investigated specific predictors of parental distress, including burnout, anger aimed at children, worry, lack of social support, lower perceived self-efficacy, and difficulty to work from home. Method: In this cross-sectional, epidemiological study, we disseminate an online survey that was administered two weeks after the government-initiated physical distancing protocols were established. Data were collected from March 31 to April 7. Results: Female parents compared to male parents and parents living with more than one child per parent or child(ren) with special needs compared to those living with one or fewer children per parent reported higher levels of parental stress. Burnout and social support were further associated with parental stress. Specifically, nearly one-fourth of the parents reported that they have felt burned out or in the proximity of feeling burned out more than half the days during the social distancing interventions. Also, 29% of the parents reported that they were angrier at their child(ren) than usual during the physical distancing period. Parents with a pre-existing psychiatric diagnosis had significantly higher parental stress compared to individuals with no psychiatric diagnosis. The reported prevalence of depression and anxiety symptoms above standardized cutoff levels among the 2868 parents was 25.4% for depression and 24.1% for anxiety, with the highest prevalence score on both symptoms of anxiety (37.6%) and depression (38.5%) for the youngest parents (age group 21–30 years). Furthermore, the parents who were home with their children and predominantly followed distancing protocol by socially distancing from public activity and peers (i.e., at least 10 out of 14 days) had significantly higher symptoms of depression (29%) and anxiety (27%), compared to parents who did not isolate in the same manner (i.e., depression 13% and anxiety 15%). Conclusions: The present study reveals that home confinement during the restricted lockdown period is related to markedly high levels of parental stress, in addition to symptoms of depression and anxiety in parents. Given the detrimental effects of depression, anxiety, and parental stress on the quality of life, morbidity rates, as well as adverse child outcomes and the potential risk of child abuse and neglect, these results suggest that appropriate action should be taken to impede further development of these symptoms, as well as developing interventions aimed at vulnerable subgroups and other relevant factors associated with increased parental stress. Keywords: COVID-19 lockdown, parental stress, depression, anxiety
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/3nsda/" target="_blank">Parenting in a Pandemic: Parental Stress During the Physical Distancing Intervention Following the onset of the COVID-19 Outbreak</a>
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</div></li>
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<li><strong>Moralizing Physical Distancing during the COVID-19 Pandemic -- Personal Motivations Predict Moral Condemnation</strong> -
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<div>
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Physical distancing is a crucial aspect of most countries’ strategies to manage the COVID-19 pandemic. However, keeping distance to others in public requires significant changes in conduct and behavior relative to ordinary circumstances. Throughout history, an effective strategy to make people engage in such behavioral change has been to morally condemn those who do not behave in an appropriate way. Accordingly, here, we investigate whether physical distancing has emerged as a moralized issue during the COVID-19 pandemic, potentially explaining the massive changes in behavior that have occurred across societies to halter the spread of the pandemic. Specifically, we utilize time-sensitive, representative survey evidence from eight Western democracies to examine the extent to which people (1) find it justified to condemn those who do not keep a distance to others in public and (2) blame ordinary citizens for the severity of the pandemic. The results demonstrate that physical distancing has indeed become a moral issue in most countries in the early phases of the pandemic. Furthermore, we identify the most important predictors of moralization to be age, behavioral change, social trust, and trust in the government. Except for minor differences, this pattern is observed within all countries in the sample. While moralization was high during the first wave of the pandemic, temporal analyses also indicate that moralization is lower in the second wave of the pandemic, potentially making it more difficult to engage in sufficient behavioral changes.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/3rczg/" target="_blank">Moralizing Physical Distancing during the COVID-19 Pandemic -- Personal Motivations Predict Moral Condemnation</a>
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<li><strong>Musical Engagement and Parent-Child Attachment in Families with Young Children During the Covid-19 Pandemic</strong> -
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<div>
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The onset of the Covid-19 pandemic has disrupted the lives of families in the United States and across the world, impacting parent mental health and stress, and in turn, the parent-child relationship. Music is a common parent-child activity and has been found to positively impact relationships, but little is known about music’s role in parent-child interactions during a pandemic. The current study utilized an online questionnaire to assess the use of music in the home of young children and their parents in the USA and Canada during Covid-19 and its relationship with parents’ affective attachment with their child. Musical activity was high for both parents and children. Parents reported using music for both emotion regulation and to socially connect with their children. Parent-child musical engagement was associated with parent-child attachment, controlling for relevant parent variables including parent distress, efficacy, education and parent-child engagement in non-musical activities. These results indicate that music may be an effective tool for building and maintaining parent-child relationships during a period of uncertainty and change.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/v458u/" target="_blank">Musical Engagement and Parent-Child Attachment in Families with Young Children During the Covid-19 Pandemic</a>
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</div></li>
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<li><strong>Cultural influence on COVID-19 cognitions and growth speed: the role of cultural collectivism</strong> -
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<div>
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Many challenges faced by humans require large-scale cooperation for communal benefits. We examined what motivates such cooperation in the context of social distancing and mask wearing to reduce the transmission intensity of the novel coronavirus (COVID-19). We hypothesized that collectivism, a cultural variable characterizing the extent that individuals see themselves in relation to others, contributes to people’s willingness to engage in these behaviors. Consistent with preregistered predictions, across three studies (n=2864), including a U.S. nationally representative sample, people’s collectivist orientation is positively associated with intentions, positive beliefs, norm perceptions, and policy support for the preventive behaviors. In separate analyses at the country level (n=69 countries), more collectivist countries demonstrated lower growth rate in both COVID-19 confirmed cases and deaths. Together, these studies demonstrate the positive role of collectivism at the individual- and country-level in reducing COVID-19 transmission, and highlight the need to consider culture in public health policies and communications.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/fet6z/" target="_blank">Cultural influence on COVID-19 cognitions and growth speed: the role of cultural collectivism</a>
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</div></li>
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<li><strong>Decomposing the sources of SARS-CoV-2 fitness variation in the United States</strong> -
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<div>
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The fitness of a pathogen is composite phenotype determined by many different factors influencing growth rates both within and between hosts. Determining what factors shape fitness at the host population-level is especially challenging because both intrinsic factors like pathogen genetics and extrinsic factors such as host behaviour influence between-host transmission potential. These challenges have been highlighted by controversy surrounding the population-level fitness effects of mutations in the SARS-CoV-2 genome and their relative importance when compared against non-genetic factors shaping transmission dynamics. Building upon phylodynamic birth-death models, we develop a new framework to learn how hundreds of genetic and non-genetic factors have shaped the fitness of SARS-CoV-2. We estimate the fitness effects of all amino acid variants and several structural variants that have circulated in the United States between February and September 2020 from viral phylogenies. We also estimate how much fitness variation among pathogen lineages is attributable to genetic versus non-genetic factors such as spatial heterogeneity in transmission rates. Up to September 2020, most fitness variation between lineages can be explained by background spatial heterogeneity in transmission rates across geographic regions. Furthermore, no genetic variant including the Spike D614G mutation has had a significant effect on population-level fitness. Instead, the rapid increase in the frequency of the Spike D614G can be explained by the variant having a spatial transmission advantage due to first establishing in regions with higher transmission rates during the earliest stages of the pandemic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.14.422739v1" target="_blank">Decomposing the sources of SARS-CoV-2 fitness variation in the United States</a>
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</div></li>
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<li><strong>Recurrent emergence and transmission of a SARS-CoV-2 Spike deletion ΔH69/V70</strong> -
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<div>
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SARS-CoV-2 Spike amino acid mutations in the receptor binding domain (RBD) are becoming more common and thought to arise from immune selection pressure. Deletions in the N terminal domain are also being described, though their role is unclear. Here we report recurrent, independent acquisitions and transmissions of the Spike double deletion {Delta}H69/{Delta}V70 following receptor binding mutations such as N501Y, N439K and Y453F. In addition we report a sub-lineage of over 350 sequences bearing seven spike mutations across the RBD (N501Y, A570D), S1 ({Delta}H69/{Delta}V70) and S2 (P681H, T716I, S982A and D1118H) in England. We present data that {Delta}H69/{Delta}V70 increases Spike-mediated infectivity by approximately two fold and therefore may be a compensatory mechanism for putative antibody escape mutations in Spike. Enhanced surveillance for this deletion with and without RBD mutations should be considered as a priority.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.14.422555v1" target="_blank">Recurrent emergence and transmission of a SARS-CoV-2 Spike deletion ΔH69/V70</a>
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</div></li>
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<li><strong>SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation</strong> -
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Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and >30 spike variants. Together with cell biological and biophysical approaches, the screen reveals an essential role for membrane cholesterol in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins, and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.14.422737v1" target="_blank">SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation</a>
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<li><strong>Targeting Scavenger Receptor Type B-1 (SR-B1) and Cholesterol Inhibits Entry of SARS-CoV-2 Pseudovirus in Cell Culture</strong> -
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<div>
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The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China in late 2019 and has now caused a global pandemic. The disease caused by SARS-CoV-2 is known as COVID-19. To date, few treatments for COVID-19 have proven effective, and the current standard of care is primarily supportive. As a result, novel therapeutic strategies are in high demand. Viral entry into target cells is frequently sensitive to cell membrane lipid composition and membrane organization. Evidence suggests that cell entry of SARS-CoV-2 is most efficient when the target cell plasma membrane is replete with cholesterol; and recent data implicate cholesterol flux through the high-affinity receptor for cholesterol-rich HDL, called scavenger receptor type B-1 (SR-B1), as critical for SARS-CoV-2 entry. Here, we demonstrate that a cholesterol-poor synthetic biologic high-density lipoprotein (HDL NP) targets SR-B1 and inhibits cell entry of a SARS-CoV-2 spike protein pseudovirus. Human cells expressing SR-B1 are susceptible to SARS-CoV-2 infection, and viral entry can be inhibited by 50-80% using HDL NPs in an SR-B1-dependent manner. These results indicate that HDL NP targeting of SR-B1 is a powerful potential therapy to combat COVID-19 and other viral diseases.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.14.420133v1" target="_blank">Targeting Scavenger Receptor Type B-1 (SR-B1) and Cholesterol Inhibits Entry of SARS-CoV-2 Pseudovirus in Cell Culture</a>
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</div></li>
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<li><strong>Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation</strong> -
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<div>
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SARS-CoV-2, the virus that has caused the COVID-19 pandemic, robustly activates the host immune system in critically ill patients. Understanding how the virus engages the immune system will facilitate the development of needed therapeutic strategies. Here we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins Spike (S) and Envelope (E) activate the key immune signaling interferon (IFN) pathway in both immune and epithelial cells independent of viral infection and replication. These proteins induce reactive oxidative species generation and increases in human and murine specific IFN-responsive cytokines and chemokines, similar to their upregulation in critically ill COVID-19 patients. Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators as the activation induced by S is dependent on IRF3, TBK1, and MYD88 while that of E is largely MYD88 independent. Furthermore, these viral surface proteins, specifically E, induced peribronchial inflammation and pulmonary vasculitis in a mouse model. Finally we show that the organized inflammatory infiltrates are dependent on type I IFN signaling, specifically in lung epithelial cells. These findings underscore the role of SARS-CoV-2 surface proteins, particularly the understudied E protein, in driving cell specific inflammation and their potential for therapeutic intervention.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.14.422710v1" target="_blank">Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation</a>
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<li><strong>Modelling the impact of travel restrictions on COVID-19 cases in Newfoundland and Labrador</strong> -
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In many jurisdictions, public health authorities have implemented travel restrictions to reduce coronavirus disease 2019 (COVID19) spread. Policies that restrict travel within countries have been implemented, but the impact of these restrictions is not well known. On May 4th, 2020, Newfoundland and Labrador (NL) implemented travel restrictions such that non-residents were required to have exemptions to enter the province. We fit a stochastic epidemic model to data describing the number of active COVID19 cases in NL from March 14th - May 4th. We then predicted possible outbreaks over 9 weeks, with and without the travel restrictions, and for contact rates 40% to 70% of pre-pandemic levels. Our results suggest that the travel restrictions reduced the mean number of clinical COVID-19 cases in NL by 92%. Furthermore, without the travel restrictions there is a substantial risk of very large outbreaks. Using epidemic modelling, we show how the NL COVID19 outbreak could have unfolded had the travel restrictions not been implemented. Both physical distancing and travel restrictions affect the local dynamics of the epidemic. Our modelling shows that the travel restrictions are a plausible reason for the few reported COVID19 cases in NL after May 4th.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.09.02.20186874v2" target="_blank">Modelling the impact of travel restrictions on COVID-19 cases in Newfoundland and Labrador</a>
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</div></li>
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<li><strong>Computational Analysis of Dynamic Allostery and Control in the three SARS-CoV-2 non-structural proteins</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the COVID-19 pandemic, has no vaccine or antiviral drugs available to the public, at the time of writing. The non-structural proteins of the virus are promising drug targets because of their vital role in the viral cycle. A significant body of work has been focused on finding inhibitors which covalently and competitively bind the active site of the non-structural proteins, but little has been done to address regions other than the active site, i.e. for non-competitive inhibition. Here we extend previous work on the SARS-CoV-2 Mpro (nsp5) to three other SARS-CoV-2 proteins: host shutoff factor (nsp1), papain-like protease (nsp3, also known as PLpro) and RNA-dependent RNA-polymerase (nsp12, also known as RdRp) in complex with nsp7 and nsp8 cofactors. Using open-source software (DDPT) to construct Elastic Network Models (ENM) of the chosen proteins we analyse their fluctuation dynamics and thermodynamics, as well as using this protein family to study convergence and robustness of the ENM. Exhaustive 2-point mutational scans of the ENM and their effect on fluctuation free energies suggest several new candidate regions, distant from the active site, for control of the function of the proteins, which may assist the drug development based on the current small molecule binding screens. The results also provide new insights, including non-additive effects of double-mutation or inhibition, into the active biophysical research field of protein fluctuation allostery and its underpinning dynamical structure.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.12.422477v1" target="_blank">Computational Analysis of Dynamic Allostery and Control in the three SARS-CoV-2 non-structural proteins</a>
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<li><strong>Hepatitis C Virus Drugs Simeprevir and Grazoprevir Synergize with Remdesivir to Suppress SARS-CoV-2 Replication in Cell Culture</strong> -
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<div>
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Effective control of COVID-19 requires antivirals directed against SARS-CoV-2 virus. Here we assess ten available HCV protease inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS-CoV-2 Mpro and HCV NS3/4A proteases, and virtual docking experiments show that all ten HCV drugs can potentially bind into the Mpro binding cleft. Seven of these HCV drugs inhibit SARS-CoV-2 Mpro protease activity, while four dock well into the PLpro substrate binding cleft and inhibit PLpro protease activity. These same seven HCV drugs inhibit SARS-CoV-2 virus replication in Vero and/or human cells, demonstrating that HCV drugs that inhibit Mpro, or both Mpro and PLpro, suppress virus replication. Two HCV drugs, simeprevir and grazoprevir synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, thereby increasing remdesivir inhibitory activity as much as 10-fold.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.13.422511v1" target="_blank">Hepatitis C Virus Drugs Simeprevir and Grazoprevir Synergize with Remdesivir to Suppress SARS-CoV-2 Replication in Cell Culture</a>
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<li><strong>Profiling of oral microbiota and cytokines in COVID-19 patients</strong> -
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<div>
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SARS-CoV-2 presence has been recently demonstrated in the sputum or saliva, suggesting how the shedding of viral RNA outlasts the end of symptoms. Recent data from transcriptome analysis show that oral cavity mucosa harbors high levels of ACE2 and TMPRSS2, highlighting its role as a double-edged sword for SARS-CoV-2 body entrance or interpersonal transmission. In the present study, for the first time, we demonstrate the oral microbiota structure and inflammatory profile of COVID-19 patients. Hospitalized COVID-19 patients and matched healthy controls underwent naso/oral-pharyngeal and oral swabs. Microbiota structure was analyzed by 16S rRNA V2 automated targeted sequencing, while oral and sera concentrations of 27 cytokines were assessed using magnetic bead-based multiplex immunoassays. A significant diminution in species richness was observed in COVID-19 patients, along with a marked difference in beta-diversity. Species such as Prevotella salivae and Veillonella infantium were distinctive for COVID-19 patients, while Neisseria perflava and Granulicatella elegans were predominant in controls. Interestingly, these two groups of oral species oppositely clustered within the bacterial network, defining two distinct Species Interacting Group (SIGs). Pro-inflammatory cytokines were distinctive for COVID-19 in both oral and serum samples, and we found a specific bacterial consortium able to counteract them, following a novel index called C4 firstly proposed here. We even introduced a new parameter, named CytoCOV, able to predict COVID-19 susceptibility for an unknown subject at 71% of power with an AUC equal to 0.995. This pilot study evidenced a distinctive oral microbiota composition in COVID-19 subjects, with a definite structural network in relation to secreted cytokines. Our results would pave the way for a theranostic approach in fighting COVID-19, trying to enlighten the intimate relationship among microbiota and SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.13.422589v1" target="_blank">Profiling of oral microbiota and cytokines in COVID-19 patients</a>
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<li><strong>Neuroinvasion and encephalitis following intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 infection in the central nervous system. Herein, using K18-hACE2 mice, we demonstrate that SARS-CoV-2 neuroinvasion and encephalitis is associated with mortality in these mice. Intranasal infection of K18-hACE2 mice with 105 plaque-forming units of SARS-CoV-2 resulted in 100% mortality by day 6 after infection. The highest virus titers in the lungs were observed at day 3 and declined at days 5 and 6 after infection. In contrast, very high levels of infectious virus were uniformly detected in the brains of all the animals at days 5 and 6. Onset of severe disease in infected mice correlated with peak viral levels in the brain. SARS-CoV-2-infected mice exhibited encephalitis hallmarks characterized by production of cytokines and chemokines, leukocyte infiltration, hemorrhage and neuronal cell death. SARS-CoV-2 was also found to productively infect cells within the nasal turbinate, eye and olfactory bulb, suggesting SARS-CoV-2 entry into the brain by this route after intranasal infection. Our data indicate that direct infection of CNS cells together with the induced inflammatory response in the brain resulted in the severe disease observed in SARS-CoV-2-infected K18-hACE2 mice.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.14.422714v1" target="_blank">Neuroinvasion and encephalitis following intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice</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>Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Silmitasertib; Drug: SOC<br/><b>Sponsor</b>: Chris Recknor, MD<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: SARS-CoV-2 convalescent plasma; Other: Standard of care<br/><b>Sponsors</b>: Joakim Dillner; Karolinska Institutet; Danderyd Hospital; Falu Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Group A (AG0302-COVID19); Biological: Group A (Placebo); Biological: Group B (AG0302-COVID19); Biological: Group B (Placebo)<br/><b>Sponsors</b>: AnGes, Inc.; Japan Agency for Medical Research and Development<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers</strong> - <b>Condition</b>: COVID 19 Vaccine<br/><b>Intervention</b>: Biological: BCG vaccine<br/><b>Sponsors</b>: Universidade Federal do Rio de Janeiro; Ministry of Science and Technology, Brazil<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: bamlanivimab<br/><b>Sponsors</b>: Daniel Griffin, MD PhD; Eli Lilly and Company; Optum, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Changes in Viral Load in COVID-19 After Probiotics</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Dietary supplementation with probiotic GASTEEL PLUS in patients with covid disease admitted to hospital<br/><b>Sponsors</b>: Hospital de Sagunto; Biopolis S.L.; Laboratorios Heel España<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C; Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose; Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment<br/><b>Sponsor</b>: Xi'an International Medical Center Hospital<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IFN-beta 1b and Remdesivir for COVID19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Interferon beta-1b; Drug: Remdesivir<br/><b>Sponsor</b>: The University of Hong Kong<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 And Geko Evaluation: The CAGE Study</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Device: geko T3<br/><b>Sponsor</b>: Lawson Health Research Institute<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: AT-100<br/><b>Sponsor</b>: Airway Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>LYT-100 in Post-acute COVID-19 Respiratory Disease</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: LYT-100; Other: Placebo<br/><b>Sponsors</b>: PureTech; Clinipace Worldwide; Novotech (Australia) Pty Limited<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids -</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Omegaven®; Drug: Sodium chloride<br/><b>Sponsor</b>: Karolinska University Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>WHO COVID-19 Solidarity Trial for COVID-19 Treatments</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Remdesivir; Drug: Acalabrutinib; Drug: Interferon beta-1a; Other: Standard of Care<br/><b>Sponsor</b>: The University of The West Indies<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Apixaban 2.5 MG; Drug: Placebo<br/><b>Sponsors</b>: Thomas Ortel, M.D., Ph.D.; National Heart, Lung, and Blood Institute (NHLBI)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mushroom-based Product for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: FoTv<br/><b>Sponsors</b>: Gordon Saxe; University of California, Los Angeles; University of California, Irvine<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dual Targeting of 3CL(pro) and PL(pro) of SARS-CoV-2: A Novel Structure-Based Design Approach to treat COVID-19</strong> - With the rapid growth of the COVID-19 (coronavirus disease 2019) pandemic across the globe, therapeutic attention must be directed to fight the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, developing new antiviral drugs and vaccine development is time-consuming, so one of the best solutions to tackle this virus at present is to repurpose ready-to-use drugs. This paper proposes the repurposing of the Food and Drug Administration (FDA)-approved, purchasable, and...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protoporphyrin IX and verteporfin potently inhibit SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2</strong> - The SARS-CoV-2 infection is spreading rapidly worldwide. Efficacious antiviral therapeutics against SARS-CoV-2 is urgently needed. Here, we discovered that protoporphyrin IX (PpIX) and verteporfin, two FDA-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 µmol/Land 0.31 µmol/L respectively, and their EC50 values of reduction of viral RNA were at nanomolar concentrations. The selectivity indices of PpIX and verteporfin were 952.74 and 368.93,...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Autophagy in T cells from aged donors is maintained by spermidine, and correlates with function and vaccine responses</strong> - Older adults are at high risk for infectious diseases such as observed at the recent COVID-19 outbreak and vaccination seems to be the only long-term solution to the pandemic. While most vaccines are less efficacious in older adults, little is known about the molecular mechanisms that underpin this. Autophagy, a major degradation pathway and one of the few processes known to prevent aging, is critical for the maintenance of immune memory in mice. Here, we show that autophagy is specifically...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>mTOR inhibition in COVID-19: A commentary and review of efficacy in RNA viruses</strong> - In this commentary, we shed light on the role of the mammalian target of rapamycin (mTOR) pathway in viral infections. The mTOR pathway has been demonstrated to be modulated in numerous RNA viruses. Frequently, inhibiting mTOR results in suppression of virus growth and replication. Recent evidence points towards modulation of mTOR in SARS-Cov2 infection. We discuss the current literature on mTOR in SARS-Cov2 and highlight evidence in support of a role for mTOR inhibitors in the treatment of...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection</strong> - The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HMGB1 as a potential biomarker and therapeutic target for severe COVID-19</strong> - COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A feluletaktivalt XII-es veralvadasi faktor eletkortol fuggo lehetseges szerepe a "bradikininvihar" kialakitasaban COVID-19-betegekben</strong> - CONCLUSION: The targeted inhibition of activated blood coagulation factor XII may represent a new therapeutic target for COVID-19, especially for elder patients. Recently, beneficial results have already been observed by the clinical applications of recombinant C1INH and bradykinin receptor antagonists. Orv Hetil. 2020; 161(50): 2099-2103.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen-regulated gene in the prostate. Supporting a role for sex hormones, males relative to females are disproportionately affected by COVID-19 in terms of mortality and morbidity....</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects</strong> - SARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects (syncytium formation). We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced syncytium-forming...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Stapled Peptides Based on Human Angiotensin-Converting Enzyme 2 (ACE2) Potently Inhibit SARS-CoV-2 Infection In Vitro</strong> - SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as the primary receptor to enter host cells and initiate the infection. The critical binding region of ACE2 is an ∼30-amino-acid (aa)-long helix. Here, we report the design of four stapled peptides based on the ACE2 helix, which is expected to bind to SARS-CoV-2 and prevent the binding of the virus to the ACE2 receptor and disrupt the infection. All stapled peptides showed high helical contents (50 to 94% helicity). In contrast, the...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Screened antipsychotic drugs inhibit SARS-CoV-2 binding with ACE2 in vitro</strong> - AIM: The coronavirus disease 2019 (COVID-19) pandemic has swept the globe and no specific effective drug has been identified. Drug repurposing is a well-known method to address the crisis in a time-critical fashion. Antipsychotic drugs (APDs) have been reported to inhibit DNA replication of hepatitis B virus, measles virus germination, and HIV infection, along with replication of SARS-CoV and MERS-CoV, both of which interact with host cells as SARS-CoV-2.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ritonavir may inhibit exoribonuclease activity of nsp14 from the SARS-CoV-2 virus and potentiate the activity of chain terminating drugs</strong> - SARS-CoV-2is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. The nsp14 protein of SARS-CoV-2 houses a 3' to 5' exoribonuclease activity responsible for removing mismatches that arise during genome duplication. A homology model of nsp10-nsp14 complex was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp14. This exercise showed that...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral activity against Middle East Respiratory Syndrome Coronavirus by Montelukast, an anti-asthma drug</strong> - Middle East respiratory syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5 %. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrated Bioinformatics Analysis for the Screening of Associated Pathways and Therapeutic Drugs in Coronavirus Disease 2019</strong> - CONCLUSION: Some drugs selected through our methods have been proven to have antiviral effects in previous studies. We aim to use global bioinformatics analysis to provide insights to assist in the design of new drugs and provide new choices for clinical treatment.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment Options for Coronavirus Disease 2019 in Patients With Reduced or Absent Kidney Function</strong> - Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within...</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><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.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>疫苗融合蛋白</strong> - 本申请涉及一种融合蛋白，所述融合蛋白包括SARS‑CoV‑2抗原多肽和鞭毛蛋白或其片段。本申请还提供了所述融合蛋白的制备方法和用途。本申请所述的融合蛋白能够诱导机体产生针对SARS‑CoV类病毒的抗原的细胞免疫反应。</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19</strong> -</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种SARS-CoV-2假病毒小鼠体内包装系统及其制备方法</strong> - 本发明提供了一种假病毒小鼠体内包装系统的制备方法，包括以下步骤：S1基于慢病毒包装质粒系统和睡美人转座子系统构建SARS‑CoV‑2假病毒包装质粒系统，S2将步骤S1中SARS‑CoV‑2假病毒包装质粒系统与睡美人转座酶表达质粒混合通过水动力注射的方式转染小鼠肝细胞，然后睡美人转座子系统将SARS‑CoV‑2假病毒包装所需序列以剪切粘贴的方式整合到小鼠肝细胞的基因组。本发明可在小鼠体内持续制造分泌SARS‑CoV‑2假病毒，可模拟靶器官被SARS‑CoV‑2病毒持续侵入攻击的过程，从而可模拟出新冠肺炎（COVID‑19）的病理特征。基于SARS‑CoV‑2假病毒小鼠体内包装系统的动物模型安全性高，不需要P3级实验室就能开展研究。利用水动力注射的方式引入SARS‑CoV‑2假病毒包装质粒系统操作简单，成本低。</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>柴胡解毒药物组合物及其制备方法和应用</strong> - 本发明属于中药领域，具体涉及一种柴胡解毒药物组合物及其制备方法和应用，所述柴胡解毒药物组合物以质量份计由如下原料组分制成：柴胡30<sub>60份，黄芩15</sub>30份，法半夏15<sub>30份，生姜15</sub>30份，大枣5<sub>10份，枳实20</sub>40份，大黄10<sub>20份，桃仁10</sub>20份，白芍15~30份。本发明的柴胡解毒药物组合物能够显著改善普通型COVID‑19引起的咳嗽；能改善疫毒闭肺型重型COVID‑19引起的咳嗽，显著改善疫毒闭肺型重型COVID‑19引起的胸闷、气短和乏力等主要症状。另外经大量临床观察，本发明的柴胡解毒药物组合物能够显著改善疫毒闭肺型重型COVID‑19引起的发热面红，咳嗽，痰黄粘少，或痰中带血，喘憋气促，疲乏倦怠，口干苦粘，大便不畅，小便短赤等症状。</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种新型冠状病毒RBD核苷酸序列、优化方法与应用</strong> - 本发明公开了一种新型冠状病毒RBD核苷酸序列、优化方法与应用。属于基因工程技术领域。优化步骤：（1）对野生型新型冠状病毒RBD核苷酸序列进行初步优化；（2）将宿主细胞特异性高表达分泌蛋白信号肽序列进行优化；（3）将人IgG1‑Fc核苷酸序列进行优化；（4）将步骤（2）优化后的宿主细胞特异性高表达分泌蛋白信号肽核苷酸序列、步骤（1）得到的初步优化新型冠状病毒RBD核苷酸序列、连接子核苷酸序列和步骤（3）优化后的人IgG1‑Fc核苷酸序列依次连接即可。与现有技术相比，本发明的有益效果：产生的克隆表达效率比野生新型冠状病毒RBD序列提高了约12倍，比中国仓鼠密码子偏性优化序列克隆表达效率提高了2倍。</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ASSISTING COMPLEX FOR TAKING OF BIOMATERIAL FROM MOUTH IN PANDEMIC CONDITIONS</strong> - FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to methods for contactless taking of biomaterial in tested person. Taking the biomaterial in the tested person is carried out in a room located in a dirty zone and separated by a partition from the clean zone, in which there is a laboratory assistant performing the procedure using a robotic complex. Complex includes digital controller, manipulator with tool unit, small manipulator, camera, monitor, control system of digital controller, manipulator, small manipulator, and complex control system. In the partition there are two holes: one – for installation and passage of the swab, the other – for the test tube installation. In the dirty zone there is a small manipulator having two actuators: one for movement of a test tube with a swab, and the second for positioning and placing a disposable mouthpiece. EFFECT: reduced risk of laboratory assistant and tested person infection by avoiding their direct contact. 17 cl, 1 dwg</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.
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</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.
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</p></li>
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</ul>
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