Daily-Dose/archive-covid-19/03 August, 2023.html

184 lines
51 KiB
HTML
Raw Blame History

This file contains invisible Unicode characters

This file contains invisible Unicode characters that are indistinguishable to humans but may be processed differently by a computer. If you think that this is intentional, you can safely ignore this warning. Use the Escape button to reveal them.

This file contains Unicode characters that might be confused with other characters. If you think that this is intentional, you can safely ignore this warning. Use the Escape button to reveal them.

<!DOCTYPE html>
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
<meta charset="utf-8"/>
<meta content="pandoc" name="generator"/>
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
<title>03 August, 2023</title>
<style>
code{white-space: pre-wrap;}
span.smallcaps{font-variant: small-caps;}
span.underline{text-decoration: underline;}
div.column{display: inline-block; vertical-align: top; width: 50%;}
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
ul.task-list{list-style: none;}
</style>
<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
<body>
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Tetherin restricts SARS-CoV-2 replication despite antagonistic effects of Spike and ORF7a</strong> -
<div>
SARS-CoV-2 infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S) inducing lysosomal degradation of Tetherin, and ORF7a altering its glycosylation. SARS-CoV-2 ORF7a has also been shown to antagonize Tetherin. Therefore, we here investigated whether SARS-CoV-2 S is also a Tetherin antagonist and compared the abilities and mechanisms of S and ORF7a in counteracting Tetherin. SARS-CoV and SARS-CoV-2 S reduced Tetherin cell surface levels in a cell type-dependent manner, possibly related to the basal protein levels of Tetherin. In HEK293T cells, under conditions of high exogenous Tetherin expression, SARS-CoV-2 S and ORF7a reduced total Tetherin levels much more efficiently than the respective counterparts derived from SARS-CoV. Nevertheless, ORF7a from both strains was able to alter Tetherin glycosylation. The ability to decrease total protein levels of Tetherin was conserved among S proteins from different SARS-CoV-2 variants (D614G, Cluster 5, , {gamma}, {delta}, o). While SARS-CoV-2 S and ORF7a both colocalized with Tetherin, only ORF7a directly interacted with the restriction factor. Despite the presence of two Tetherin antagonists, however, SARS-CoV-2 replication in Caco-2 cells was further enhanced upon Tetherin knockout. Altogether, our data show that endogenous Tetherin restricts SARS-CoV-2 replication, and that the antiviral activity of Tetherin is partially counteracted by two viral antagonists with differential and complementary modes of action, S and ORF7a.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.28.550997v1" target="_blank">Tetherin restricts SARS-CoV-2 replication despite antagonistic effects of Spike and ORF7a</a>
</div></li>
<li><strong>The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions</strong> -
<div>
Dysregulated microglia activation, leading to neuroinflammation, is currently considered to be of major relevance in the development and progression of neurodegenerative diseases. The initial M1/M2 dual activation classification for microglia is now considered outdated. Even the "disease-associated microglia" (DAM) phenotype, firstly described in mice, has proven insufficient to precisely represent the multitude of microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution to the establishment of pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. The HuMicA is an invaluable resource tool used to support further advances in the study of microglia biology through healthy and disease settings.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.01.550767v1" target="_blank">The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions</a>
</div></li>
<li><strong>Frequency of Atypical Pulmonary Manifestations of COVID-19 Patients on Chest CTscan: A cross-sectional study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Chest CT examination is significant in COVID-19 diagnosis due to its high sensitivity. Although typical chest CT findings have been discussed thoroughly in the literature throughout the pandemic, we aimed to investigate the prevalence of the atypical conclusions during the start of the Omicron variant insurgency and compare the results to studies conducted before its outbreak. Methods: 606 confirmed COVID-19 cases were included in this study based on inclusion and exclusion criteria during January and February 2022. Demographic information of patients, including age and sex, was recorded. The computed tomography (CT) examination was carried out using a 100-slice scanner (Philips Brilliance 6 CT Scanner). One radiology attending and one resident evaluated SARSCoV- 2 RT-PCR-positive patients for atypical pulmonary CT findings. The obtained data were evaluated using R software version 4.1.1. Results: 55% of patients were female, and the median age was 56 (IQR: 42, 69 59% of patients had atypical findings on their pulmonary CT examination. These findings showed that pleural abnormalities were the most frequent atypicalfindings, with pleural thickening being the most common (17%). The double halo sign represented the least frequent atypical sign (0.2%). Conclusion: Atypical findings were more prevalent in this study than its predecessors, while we acknowledge that other factors, such as study design and patient population, could have impacted it. The presence of atypical signs generally was not correlated with specific demographic groups, while some of these signs were more frequent in some groups.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293261v1" target="_blank">Frequency of Atypical Pulmonary Manifestations of COVID-19 Patients on Chest CTscan: A cross-sectional study</a>
</div></li>
<li><strong>Lower Urinary Tract Symptoms in a prospective cohort of COVID-19 survivors</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Purpose: To analyze the prevalence of lower urinary tract symptoms (LUTS) in patients who survived moderate and severe forms of COVID-19 and the risk factors for LUTS six months after hospital discharge. Materials and Methods: In this prospective cohort study, patients were evaluated six months after being hospitalized due to COVID-19. LUTS were assessed using the International Prostate Symptom Score. General health was assessed through the Hospital Anxiety and Depression Scale and the EQ5D-L5 scale, which evaluates mobility, ability to perform daily activities, pain and discomfort and completed a self-perception health evaluation. Results: Of 255 participants, 54.1% were men and the median age was 57.3 [44.3 / 66.6] years. Pre-existing comorbidities included diabetes (35.7%), hypertension (54.5%), obesity (30.2%) and physical inactivity (65.5%). 124 (48.6%) had a hospital stay &gt;15 days, 181 (71.0%) were admitted to an ICU and 124 (48.6%) needed mechanical ventilation. Median IPSS score was 6 [3-11] and did not differ between men and women. Moderate to severe LUTS affected 108 (42.4%) patients (40.6% men and 44.4% women; p=0.610). Nocturia (58.4%) and frequency (45.9%) were the most prevalent symptoms and urgency was the only symptom that affected men (29.0%) and women (44.4%) differently (p=0.013). LUTS significantly impacted the quality of life of 60 (23.5%) patients with women more severely affected (p=0.004). Preexisting diabetes, hypertension and self-perception of worse general health were associated with LUTS. Conclusions: LUTS are highly prevalent and bothersome six months after hospitalization due to COVID-19. Assessment of LUTS may help ensure appropriate diagnosis and treatment in these patients.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.01.23293500v1" target="_blank">Lower Urinary Tract Symptoms in a prospective cohort of COVID-19 survivors</a>
</div></li>
<li><strong>Graphical Learning and Causal Inference for Drug Repurposing</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Abstract Gene expression profiles that connect drug perturbations, disease gene expression signatures, and clinical data are important for discovering potential drug repurposing indications. However, the current approach to gene expression reversal has several limitations. First, most methods focus on validating the reversal expression of individual genes. Second, there is a lack of causal approaches for identifying drug repurposing candidates. Third, few methods for passing and summarizing information on a graph have been used for drug repurposing analysis, with classical network propagation and gene set enrichment analysis being the most common. Fourth, there is a lack of graph-valued association analysis, with current approaches using real-valued association analysis one gene at a time to reverse abnormal gene expressions to normal gene expressions. To overcome these limitations, we propose a novel causal inference and graph neural network (GNN)-based framework for identifying drug repurposing candidates. We formulated a causal network as a continuous constrained optimization problem and developed a new algorithm for reconstructing large-scale causal networks of up to 1,000 nodes. We conducted large-scale simulations that demonstrated good false positive and false negative rates. To aggregate and summarize information on both nodes and structure from the spatial domain of the causal network, we used directed acyclic graph neural networks (DAGNN). We also developed a new method for graph regression in which both dependent and independent variables are graphs. We used graph regression to measure the degree to which drugs reverse altered gene expressions of disease to normal levels and to select potential drug repurposing candidates. To illustrate the application of our proposed methods for drug repurposing, we applied them to phase I and II L1000 connectivity map perturbational profiles from the Broad Institute LINCS, which consist of gene-expression profiles for thousands of perturbagens at a variety of time points, doses, and cell lines, as well as disease gene expression data under-expressed and over-expressed in response to SARS-CoV-2.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.29.23293346v1" target="_blank">Graphical Learning and Causal Inference for Drug Repurposing</a>
</div></li>
<li><strong>Loss of severe respiratory syncytial virus infection-associated antibody function during the peak of the COVID-19 pandemic mitigation measures</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Studies have linked reduced respiratory syncytial virus-specific Fc-mediated phagocytic function and complement deposition to more severe infection. This study shows a loss of these functions during the first year of COVID-19 pandemic. These findings corroborate other data supporting a general waning of RSV antibody functions in absence of viral circulation.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.30.23292881v1" target="_blank">Loss of severe respiratory syncytial virus infection-associated antibody function during the peak of the COVID-19 pandemic mitigation measures</a>
</div></li>
<li><strong>Prevalence of long-term symptoms varies by using different post-COVID-19 definitions in positively and negatively tested adults: the PRIME post-COVID study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Abstract Background Long-term symptoms after a SARS-CoV-2 infection (i.e., post-COVID-19 condition or long COVID), constitute a substantial public health problem. Yet, the prevalence remains currently unclear as different case definitions are used, and negatively tested controls are lacking. We aimed to estimate post-COVID-19 condition prevalence using six definitions. Methods The Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study is a population-based sample of COVID-19 tested adults. End 2021, 61,655 adults were invited to complete an online questionnaire, including 44 symptoms plus a severity score (0-10) per symptom. The prevalence was calculated in both positively and negatively tested adults, stratified by time since their COVID-19 test (3-5, 6-11 or ≥12 months ago). Results In positives (n=7,405; 75.6%), the prevalence of long-term symptoms was between 26.9% and 64.1% using the six definitions, while in negatives (n=2,392; 24.4%) the prevalence varied between 11.4% and 32.5%. The prevalence of long-term symptoms potentially accountable to COVID-19 ranged from 17.9% to 26.3%. Conclusion There is a (substantial) variation in prevalence estimates by using different definitions as is current practice, showing limited overlap between definitions, indicating that the essential post-COVID-19 condition criteria are still unclear. Including negatives is important to determine long-term symptoms accountable to COVID-19. Trial registration ClinicalTrials.gov Identifier: NCT05128695.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.27.23293244v1" target="_blank">Prevalence of long-term symptoms varies by using different post-COVID-19 definitions in positively and negatively tested adults: the PRIME post-COVID study</a>
</div></li>
<li><strong>Growth media affects susceptibility of air-lifted human nasal epithelial cell cultures to SARS-CoV2, but not Influenza A, virus infection.</strong> -
<div>
Primary differentiated human epithelial cell cultures have been widely used by researchers to study viral fitness and virus-host interactions, especially during the COVID19 pandemic. These cultures recapitulate important characteristics of the respiratory epithelium such as diverse cell type composition, polarization, and innate immune responses. However, standardization and validation of these cultures remains an open issue. In this study, two different expansion medias were evaluated and the impact on the resulting differentiated culture was determined. Use of both Airway and Ex Plus media types resulted in high quality, consistent cultures that were able to be used for these studies. Upon histological evaluation, Airway-grown cultures were more organized and had a higher proportion of basal progenitor cells while Ex Plus- grown cultures had a higher proportion terminally differentiated cell types. In addition to having different cell type proportions and organization, the two different growth medias led to cultures with altered susceptibility to infection with SARS-CoV-2 but not Influenza A virus. RNAseq comparing cultures grown in different growth medias prior to differentiation uncovered a high degree of differentially expressed genes in cultures from the same donor. RNAseq on differentiated cultures showed less variation between growth medias but alterations in pathways that control the expression of human transmembrane proteases including TMPRSS11 and TMPRSS2 were documented. Enhanced susceptibility to SARS-CoV-2 cannot be explained by altered cell type proportions alone, rather serine protease cofactor expression also contributes to the enhanced replication of SARS-CoV-2 as inhibition with camostat affected replication of an early SARS-CoV-2 variant and a Delta, but not Omicron, variant showed difference in replication efficiency between culture types. Therefore, it is important for the research community to standardize cell culture protocols particularly when characterizing novel viruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.31.551381v1" target="_blank">Growth media affects susceptibility of air-lifted human nasal epithelial cell cultures to SARS-CoV2, but not Influenza A, virus infection.</a>
</div></li>
<li><strong>Jointly modeling deep mutational scans identifies shifted mutational effects among SARS-CoV-2 spike homologs</strong> -
<div>
Deep mutational scanning (DMS) is a high-throughput experimental technique that measures the effects of thousands of mutations to a protein. These experiments can be performed on multiple homologs of a protein or on the same protein selected under multiple conditions. It is often of biological interest to identify mutations with shifted effects across homologs or conditions. However, it is challenging to determine if observed shifts arise from biological signal or experimental noise. Here, we describe a method for jointly inferring mutational effects across multiple DMS experiments while also identifying mutations that have shifted in their effects among experiments. A key aspect of our method is to regularize the inferred shifts, so that they are nonzero only when strongly supported by the data. We apply this method to DMS experiments that measure how mutations to spike proteins from SARS-CoV-2 variants (Delta, Omicron BA.1, and Omicron BA.2) affect cell entry. Most mutational effects are conserved between these spike homologs, but a fraction have markedly shifted. We experimentally validate a subset of the mutations inferred to have shifted effects, and confirm differences of &gt;1,000-fold in the impact of the same mutation on spike-mediated viral infection across spikes from different SARS-CoV-2 variants. Overall, our work establishes a general approach for comparing sets of DMS experiments to identify biologically important shifts in mutational effects.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.31.551037v1" target="_blank">Jointly modeling deep mutational scans identifies shifted mutational effects among SARS-CoV-2 spike homologs</a>
</div></li>
<li><strong>Single-cell RNA sequencing reveals characteristics of myeloid cells in pulmonary post-acute sequelae of SARS-CoV-2</strong> -
<div>
Background: Although our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complication in COVID-19 infection remain unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequelae of SARS-CoV-2 infection with persistent pulmonary symptoms (PPASC). However, the dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown. Results: To characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from participants naive to SARS-CoV-2 (Control) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC). We analyzed more than 34,139 PBMCs by integrating our dataset with previously reported control datasets (GSM4509024) cell distribution. In total, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14+/CD16+monocytes and dendritic cells) was increased in PPASC compared to controls. MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis-related (VEGF, WNT, and SMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. In PPASC, we observed interactive VEGF ligand-receptor pairs among MLCs, and network modules in CD14+ (cluster 4) and CD16+ (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID-19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS-CoV-2 naive samples. Conclusion: This study offers valuable insights into the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests their potential role as a driver of PPASC.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.31.551349v1" target="_blank">Single-cell RNA sequencing reveals characteristics of myeloid cells in pulmonary post-acute sequelae of SARS-CoV-2</a>
</div></li>
<li><strong>Integrated Organ Immunity: Antigen-specific CD4-T cell-derived IFN-γ induced by BCG imprints prolonged lung innate resistance against respiratory viruses</strong> -
<div>
Bacille Calmette-Guerin (BCG) vaccination can confer non-specific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. Here, we show that mice immunized intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with SARS-CoV-2 and influenza. Protection was first evident between 14 - 21 days post vaccination, and lasted for at least 42 days. Remarkably, BCG induced a biphasic innate response in the lung, initially at day 1 and a subsequent prolonged phase starting at ~15 days post vaccination, and robust antigen-specific Th1 responses. MyD88-dependent TLR signaling was essential for the induction of the innate and Th1 responses, and protection against SARS-CoV-2. Depletion of CD4+ T cells or IFN-{gamma} activity prior to infection obliterated innate activation and protection. Single cell and spatial transcriptomics revealed CD4-dependent expression of interferon-stimulated genes (ISGs) in myeloid, type II alveolar and lung epithelial cells. Thus, BCG elicits "integrated organ immunity" where CD4+ T cells act on local myeloid and epithelial cells to imprint prolonged antiviral innate resistance.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.31.551354v1" target="_blank">Integrated Organ Immunity: Antigen-specific CD4-T cell-derived IFN-γ induced by BCG imprints prolonged lung innate resistance against respiratory viruses</a>
</div></li>
<li><strong>Strong immunogenicity &amp; protection in mice with PlaCCine: A COVID-19 DNA vaccine formulated with a functional polymer</strong> -
<div>
DNA- based vaccines have demonstrated the potential as a safe and effective modality. PlaCCine, a DNA-based vaccine approach described subsequently relies on a synthetic DNA delivery system and is independent of virus or device. The synthetic functionalized polymer combined with DNA demonstrated stability over 12 months at 4C and for one month at 25C. Transfection efficiency compared to naked DNA increased by 5-15-fold in murine skeletal muscle. Studies of DNA vaccines expressing spike proteins from variants D614G (pVAC15), Delta (pVAC16), or a D614G + Delta combination (pVAC17) were conducted. Mice immunized intramuscular injection (IM) with pVAC15, pVAC16 or pVAC17 formulated with functionalized polymer and adjuvant resulted in induction of spike-specific humoral and cellular responses. Antibody responses were observed after one immunization. And endpoint IgG titers increased to greater than 1x 105 two weeks after the second injection. Neutralizing antibodies as determined by a pseudovirus competition assay were observed following vaccination with pVAC15, pVAC16 or pVAC17. Spike specific T cell immune responses were also observed following vaccination and flow cytometry analysis demonstrated the cellular immune responses included both CD4 and CD8 spike specific T cells. The immune responses in vaccinated mice were maintained for up to 14 months after vaccination. In an immunization and challenge study of K18 hACE2 transgenic mice pVAC15, pVAC16 and pVAC17 induced immune responses lead to decreased lung viral loads by greater than 90% along with improved clinical score. These findings suggest that PlaCCine DNA vaccines are effective and stable and further development against emerging SARS-CoV-2 variants is warranted.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.01.551509v1" target="_blank">Strong immunogenicity &amp; protection in mice with PlaCCine: A COVID-19 DNA vaccine formulated with a functional polymer</a>
</div></li>
<li><strong>Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes</strong> -
<div>
RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consists of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and in silico sequence analyses, we find that the sensitivity of the IAV H3N2 RNA polymerase to t-loops increased between isolates from 1968 and 2017, whereas the total free energy of t-loops in the IAV H3N2 genome was reduced. This reduction is particularly prominent in the PB1 gene. In H1N1 IAV, we find two separate reductions in t-loop free energy, one following the 1918 pandemic and one following the 2009 pandemic. No destabilization of t-loops is observed in the IBV genome, whereas analysis of SARS-CoV-2 isolates reveals destabilization of viral RNA structures. Overall, we propose that a loss of free energy in the RNA genome of emerging respiratory RNA viruses may contribute to the adaption of these viruses to the human population.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.25.542331v2" target="_blank">Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes</a>
</div></li>
<li><strong>The infectivity of SARS-CoV-2 progeny virions requires the activity of host cell N-myristoyltransferases and it is severely compromised by their inhibition</strong> -
<div>
Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Despite vaccinations, the development and use of neutralising antibodies against the viral surface spike proteins, and small molecule inhibitors targeting the viral replication machinery, COVID-19 remains a global public health crisis. Emerging mutations in the viral genome have the potential to reduce prophylactic and therapeutic efficacy of virus-directed treatments. Targeting host cell factors required for infection could, therefore, be a potential strategy to overcome this problem since mutations in the viral genome are unlikely to bypass the requirement for the targeted host factor or function. The enzymatic activity of N-myristoyltransferases (NMTs) are essential to mediate stable membrane binding and function of a diverse class of cellular proteins, many of which regulate intracellular membrane trafficking. Here we report that nanomolar concentrations of the NMT inhibitor IMP-1088 inhibited SARS-CoV-2 spreading in human cells by compromising the infectivity of released viral particles, which was reduced by up to 90%. IMP-1088 also inhibited human Respiratory syncytial virus, the main cause of viral death in infants world-wide, but not the mosquito-delivered alphavirus Semliki Forest virus and the vesiculovirus Vesicular stomatitis virus. The antiviral effect of IMP-1088 against SARS-CoV-2 displayed remarkably slow reversibility, was well tolerated by cells, and is, therefore, a promising candidate for COVID-19 prophylaxis and therapy.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.03.530798v2" target="_blank">The infectivity of SARS-CoV-2 progeny virions requires the activity of host cell N-myristoyltransferases and it is severely compromised by their inhibition</a>
</div></li>
<li><strong>SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID-19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 21 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P&lt;0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293441v1" target="_blank">SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: Freeze-dried Mare Milk (Saumal)<br/><b>Sponsor</b>:   Asfendiyarov Kazakh National Medical University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Exercise Training on Patients With Long COVID-19</strong> - <b>Condition</b>:   Long COVID-19<br/><b>Intervention</b>:   Behavioral: Exercise training<br/><b>Sponsor</b>:   Guangdong Provincial Peoples 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>A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: mRNA-CR-04 vaccine 10μg;   Biological: mRNA-CR-04 vaccine 30μg;   Biological: mRNA-CR-04 vaccine 100μg;   Drug: Placebo<br/><b>Sponsor</b>:   GlaxoSmithKline<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 Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine;   Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br/><b>Sponsor</b>:   Novavax<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>Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome</strong> - <b>Conditions</b>:   Fatigue;   Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>:   Procedure: Immunoadsorption vs. sham immunoadsorption<br/><b>Sponsor</b>:   Hannover Medical School<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>Non-ventilated Prone Positioning in the COVID-19 Population</strong> - <b>Conditions</b>:   COVID-19;   Proning;   Oxygenation;   Length of Stay<br/><b>Interventions</b>:   Other: Proning group;   Other: Control group<br/><b>Sponsor</b>:   Baylor St. Lukes Medical Center<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19</strong> - <b>Conditions</b>:   COVID-19;   Delirium;   Critical Illness<br/><b>Interventions</b>:   Combination Product: Active HD-tDCS;   Combination Product: Sham HD-tDCS<br/><b>Sponsors</b>:   Suellen Andrade;   City University of New York<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 on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults</strong> - <b>Condition</b>:   SARS-CoV-2<br/><b>Interventions</b>:   Biological: CV0701 Bivalent High dose;   Biological: CV0701 Bivalent Medium dose;   Biological: CV0701 Bivalent Low dose;   Biological: CV0601 Monovalent High dose;   Biological: Control vaccine<br/><b>Sponsors</b>:   GlaxoSmithKline;   CureVac<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>RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms</strong> - <b>Conditions</b>:   Long COVID-19;   Long COVID<br/><b>Interventions</b>:   Drug: Paxlovid 25 day dosing;   Drug: Paxlovid 15 day dosing;   Drug: Control<br/><b>Sponsor</b>:   Kanecia Obie Zimmerman<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>PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>:   SARS-CoV-2<br/><b>Interventions</b>:   Drug: Upamostat;   Drug: Placebo (PO)<br/><b>Sponsors</b>:   Henry M. Jackson Foundation for the Advancement of Military Medicine;   Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies;   FHI Clinical, Inc.;   RedHill Biopharma Limited<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>RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>:   Long COVID;   Long Covid19;   Long Covid-19<br/><b>Interventions</b>:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham<br/><b>Sponsor</b>:   Duke University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Directed Topical Drug Delivery for Treatment for PASC Hyposmia</strong> - <b>Condition</b>:   Post Acute Sequelae Covid-19 Hyposmia<br/><b>Interventions</b>:   Drug: Beclomethasone;   Other: Placebo;   Device: Microsponge<br/><b>Sponsor</b>:   Duke University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>:   Long COVID;   Long Covid19;   Long Covid-19<br/><b>Interventions</b>:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham<br/><b>Sponsor</b>:   Duke University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of COVID-19 on Sinus Augmentation Surgery</strong> - <b>Condition</b>:   Bone Loss<br/><b>Interventions</b>:   Procedure: Sinus lift in patients with positive COVID-19 history;   Procedure: Sinus lift with negative COVID-19 history<br/><b>Sponsor</b>:   Cairo University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telerehabilitation for Post COVID-19 Condition</strong> - <b>Conditions</b>:   Long COVID;   Chronic Fatigue Syndrome<br/><b>Intervention</b>:   Other: Telerehabilitation program based on cardiorespiratory principles<br/><b>Sponsors</b>:   Université de Sherbrooke;   Hotel Dieu Hospital<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>Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation</strong> - NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2O-methyl-transferase (2O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM…</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>Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease</strong> - Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that…</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>Crystal structures of main protease (M<sup>pro</sup>) mutants of SARS-CoV-2 variants bound to PF-07304814</strong> - There is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (M^(pro)) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 M^(pro) with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment…</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>Direct blue 53, a biological dye, inhibits SARS-CoV-2 infection by blocking ACE2 and spike interaction in vitro and in vivo</strong> - COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five…</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>Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model</strong> - Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were…</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>Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury</strong> - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis</strong> - CONCLUSIONS: Potentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions.</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 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones</strong> - The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds,…</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 a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection</strong> - We previously identified GAPDH as one of the cyclic adenosine diphosphoribose (cADPR)s binding proteins and found that GAPDH participates in cADPR-mediated Ca^(2+) release from ER via ryanodine receptors (RyRs). Here we aimed to chemically synthesize and pharmacologically characterize novel cADPR analogues. Based on the simulated cADPR-GAPDH complex structure, we performed the structure-based drug screening, identified several small chemicals with high docking scores to cADPRs binding pocket…</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>Discovery and evaluation of active compounds from Xuanfei Baidu formula against COVID-19 via SARS-CoV-2 M<sup>pro</sup></strong> - CONCLUSION: Acteoside is regarded as a representative active natural compound in XFBD to inhibit replication of SARS-CoV-2, which provides the antiviral evidence and some insights into the identification of SARS-CoV-2 M^(pro) natural inhibitors.</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>Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2</strong> - CONCLUSION: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.</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>Deuteration for Metabolic Stabilization of SARS-CoV-2 Inhibitors GC373 and Nirmatrelvir</strong> - Nirmatrelvir and GC373 inhibit the SARS-CoV-2 3CL protease and hinder viral replication in COVID-19. As nirmatrelvir in Paxlovid is oxidized by cytochrome P450 3A4, ritonavir is coadministered to block this. However, ritonavir undesirably alters the metabolism of other drugs. Hydrogens can be replaced with deuterium in nirmatrelvir and GC373 to slow oxidation. Results show that deuterium slows oxidation of nirmatrelvir adjacent to nitrogen by 40% and that the type of warhead can switch the site…</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>Structures of SARS-CoV-2 N7-methyltransferase with DOT1L and PRMT7 inhibitors provide a platform for new antivirals</strong> - The RNA N7-methyltransferase (MTase) activity of SARS-CoV-2s nsp14 protein is essential for viral replication and is a target for the development of new antivirals. Nsp14 uses S-adenosyl methionine (SAM) as the methyl donor to cap the 5 end of the SARS-CoV-2 mRNA and generates S-adenosyl homocysteine (SAH) as the reaction byproduct. Due to the central role of histone MTases in cancer, many SAM/SAH analogs with properties of cell permeability have recently been developed for the inhibition of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mega-scale desalination efficacy (Reverse Osmosis, Electrodialysis, Membrane Distillation, MED, MSF) during COVID-19: Evidence from salinity, pretreatment methods, temperature of operation</strong> - The unprecedented situation of the COVID-19 pandemic heavily polluted water bodies whereas the presence of SARS-CoV-2, even in treated wastewater in every corner of the world is reported. The main aim of the present study is to show the effectiveness and feasibility of some well-known desalination technologies which are reverse osmosis (RO), Electrodialysis (ED), Membrane Distillation (MD), multi effect distillation (MED), and multi stage flashing (MSF) during the COVID-19 pandemic. Systems</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 RBD bispecific antibody effectively neutralizes a SARS-CoV-2 Omicron variant</strong> - Potent neutralizing antibodies (nAbs) against SARS-CoV-2 are a promising therapeutic against the ongoing COVID-19 pandemic. However, the continuous emergence of neutralizing antibody escape variants makes it challenging for antibody therapeutics based on monospecific nAbs. Here, we generated an IgG-like bispecific antibody (bsAb), Bi-Nab, based on a pair of human neutralizing antibodies targeting multiple and invariant sites of the spike receptor binding domain (RBD): 35B5 and 32C7. We…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<script>AOS.init();</script></body></html>