Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• PARA-DIPLOMACY IN TIME OF COVID-19: JAKARTA REGIONAL GOVERNMENT’S OBJECTIVES IN HOSTING INTERNATIONAL YOUTH CHAMPIONSHIP -
  The Novel Corona Virus Disease or COVID-19 has caused unprecedented huge impacts and affected all aspects of governance including the relations among countries. Amid the crisis, sub-national governments have demonstrated their international engagements and innovations in order to respond to the pandemic. Jakarta as the largest city and the capital city of the Republic of Indonesia became the national attention in early of the pandemic due to its functional position as the main gate of international mobility. However, the region held an international event called the International Youth Championship while the pandemic still existed. This research aimed to describe the region’s objectives to carry out the event as a para-diplomacy practice. This research applied the qualitative research method with a descriptive analysis. In addition, the research utilized para-diplomacy concept as a theoretical tool to help describe such objectives. This research found that the regional government had a number of objectives in hosting the event; promoting the success of handing the COVID-19, promoting sports tourism in the post-pandemic, and introducing a new ‘green’ icon of the region. Those objectives belong to the economic and cultural dimension of para-diplomacy. This paper argues that Indonesian para-diplomacy is an asset inasmuch as the national government can harvest benefits from sub-national governments’ para-diplomatic activities.
  🖺 Full Text HTML: PARA-DIPLOMACY IN TIME OF COVID-19: JAKARTA REGIONAL GOVERNMENT’S OBJECTIVES IN HOSTING INTERNATIONAL YOUTH CHAMPIONSHIP
• The dynamic relationship between COVID-19 cases and SARS-CoV-2 wastewater concentrations across time and space: considerations for model training data sets -

  During the COVID-19 pandemic, wastewater-based surveillance has been used alongside diagnostic testing to monitor infection rates. With the decline in cases reported to public health departments due to at-home testing, wastewater data may serve as the primary input for epidemiological models, but training these models is not straightforward. We explored factors affecting noise and bias in the ratio between wastewater and case data collected in 26 sewersheds in California from October 2020 to March 2022. The strength of the relationship between wastewater and case data appeared dependent on sampling frequency and population size, but was not increased by wastewater normalization to flow rate or case count normalization to testing rates. Additionally, the lead and lag times between wastewater and case data varied over time and space, and the ratio of log-transformed individual cases to wastewater concentrations changed over time. This ratio increased sequentially in the Epsilon/Alpha, Delta, and Omicron BA.1 variant surges of COVID-19 and was also related to the diagnostic testing rate. Based on this analysis, we present a framework of scenarios describing the dynamics of the case to wastewater ratio to aid in data handling decisions for ongoing modeling efforts.

  🖺 Full Text HTML: The dynamic relationship between COVID-19 cases and SARS-CoV-2 wastewater concentrations across time and space: considerations for model training data sets
• An Early SARS-CoV-2 Omicron Outbreak in a Dormitory in Saint-Petersburg, Russia -

  The Omicron variant of SARS-CoV-2 has rapidly spread globally in late 2021 - early 2022, displacing the previously prevalent Delta variant. Before December 16, 2021, community transmission had already been observed in tens of countries globally. However, in Russia, the majority of reported cases at that time had been sporadic and associated with travel. Here, we report an Omicron outbreak at a student dormitory in Saint Petersburg between December 16 - 29, 2021, which was the earliest known instance of large-scale community transmission in Russia. Out of the 465 sampled residents of the dormitory, 180 (38.7%) tested PCR positive. Among the 118 residents for whom the variant has been tested by whole-genome sequencing, 111 (94.1%) carried the Omicron variant. Among these 111 residents, 60 (54.1%) were vaccinated or had reported previous COVID-19. Phylogenetic analysis confirmed that the outbreak was caused by a single introduction of the BA.1.1 sublineage of Omicron. The dormitory-derived clade constituted a significant proportion of BA.1.1 samples in Saint-Petersburg and has spread to other regions of Russia and other countries. The rapid spread of Omicron in a population with preexisting immunity to previous variants underlines its propensity for immune evasion.

  🖺 Full Text HTML: An Early SARS-CoV-2 Omicron Outbreak in a Dormitory in Saint-Petersburg, Russia
• Assessment of Attitude and Hesitancy Towards Covid-19 Vaccine among Hepatitis B and C Patients in Pakistan -

  OBJECTIVE: The research aimed to evaluate the attitude and perceptions towards the covid-19 vaccine among Hepatitis B and C patients in Peshawar, Khyber Pakhtunkhwa, Muzaffarabad, Azad Kashmir, Pakistan. METHODS: A survey-based study was adopted to evaluate the attitude of Hepatitis B and C patients towards immunization against covid-19 in Peshawar (KPK) and Muzaffarabad (AJK) cities of Pakistan. The study continued from January 2020 to February 2021. Participants were also assessed for their perception towards covid-19 vaccination. RESULTS: A total of 839 (33.6%) individuals participated in the study. About 52 % of Hepatitis B patients were immunized against Covid-19, whereas the number of Hepatitis C patients was recorded at around 48%. About 53.7 % of participants refused to get the vaccine without any reason. About 63.2% of patients showed concern about the insufficient data available on the vaccine safety and efficacy published by the Public Health Department. Individuals with higher education were observed to be more open towards vaccination then those without a formal education. More than half of the participants (61.5 %) were concerned about the interference of the vaccine with their hepatitis treatment whereas 54.7 % patients refused vaccine because of a poor liver condition. CONCLUSIONS: The data indicated that limited data availability regarding the vaccine efficacy in viral hepatitis patients and negative attitudes of people toward covid-19 vaccination is the main cause of Covid-19 vaccination refusal among hepatitis B and C patients. DESCRIPTORS: Hepatitis B, Hepatitis C, covid-19, immunization, vaccine refusal, Pakistan.

  🖺 Full Text HTML: Assessment of Attitude and Hesitancy Towards Covid-19 Vaccine among Hepatitis B and C Patients in Pakistan
• An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission -
  SARS-CoV-2 and its variants cause COVID-19, which is primarily transmitted through droplets and airborne aerosols. To prevent viral infection and reduce viral spread, vaccine strategies must elicit protective immunity in the airways. FcRn transfers IgG across epithelial barriers; we explore FcRn-mediated respiratory delivery of SARS-CoV-2 spike (S). A monomeric IgG Fc was fused to a stabilized S protein; the resulting S-Fc bound to S-specific antibodies (Ab) and FcRn. A significant increase in Ab responses was observed following the intranasal immunization of mice with S-Fc formulated in CpG as compared to the immunization with S alone or PBS. Furthermore, we intranasally immunize adult or aged mice and hamsters with S-Fc. A significant reduction of virus replication in nasal turbinate, lung, and brain was observed following nasal challenges with SARS-CoV-2, including Delta and Omicron variants. Intranasal immunization also significantly reduced viral transmission between immunized and naive hamsters. Protection was mediated by nasal IgA, serum-neutralizing Abs, tissue-resident memory T cells, and bone marrow S-specific plasma cells. Hence FcRn delivers an S-Fc antigen effectively into the airway and induces protection against SARS-CoV-2 infection and transmission. Based on these findings, FcRn-targeted non-invasive respiratory immunizations are superior strategies for preventing highly contagious respiratory viruses from spreading.
  🖺 Full Text HTML: An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission
• Mapping the content of comments on bioRxiv and medRxiv preprints -
  Introduction: Preprints have been increasingly used in biomedical sciences, providing the opportunity for research to be publicly assessed before journal publication. With the increase in attention over preprints during the COVID-19 pandemic, we decided to assess the content of comments left on preprint platforms. Methods: Preprints posted on bioRxiv and medRxiv in 2020 were accessed through each platform’s API, and a random sample of preprints that had received between 1 and 20 comments was analyzed. Comments were evaluated in triplicate by independent evaluators using an instrument that assessed their features and general content. Results: 7.3% of preprints received at least 1 comment during a mean follow-up of 7.5 months. Analyzed comments had a median size of 43 words. Criticisms, corrections or suggestions were the most prevalent type of content, followed by compliments or positive appraisals and questions. Most critical comments regarded interpretation, data collection and methodological design, while compliments were usually about relevance and implications. Conclusions: Only a small percentage of preprints posted in 2020 in bioRxiv and medRxiv received comments in these platforms. When present, however, these comments address content that is similar to that analyzed by traditional peer review. A more precise taxonomy of peer review functions would be desirable to describe whether post-publication peer review fulfills these roles.
  🖺 Full Text HTML: Mapping the content of comments on bioRxiv and medRxiv preprints
• SARS-CoV-2 evolves increased infection elicited cell death and fusion in an immunosuppressed individual -

  The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS-CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction of cell fusion and cell death in SARS-CoV-2 evolved from ancestral virus during long-term infection. Both cell fusion and death were reduced in Omicron BA.1 infection relative to ancestral virus. Evolved virus was isolated at different times during a 6-month infection in an immunosuppressed individual with advanced HIV disease. The virus isolated 16 days post-reported symptom onset induced fusogenicity and cell death at levels similar to BA.1. However, fusogenicity was increased in virus isolated at 6 months post-symptoms to levels intermediate between BA.1 and ancestral SARS-CoV-2. Similarly, infected cell death showed a graded increase from earlier to later isolates. These results may indicate that, at least by the cellular measures used here, evolution in long-term infection does not necessarily attenuate the virus.

  🖺 Full Text HTML: SARS-CoV-2 evolves increased infection elicited cell death and fusion in an immunosuppressed individual
• Rapid Real-time Squiggle Classification for Read Until Using RawMap -
  ReadUntil enables Oxford Nanopore Technology’s (ONT) sequencers to selectively sequence reads of target species in real-time. This enables efficient microbial enrichment for applications such as microbial abundance estimation and is particularly beneficial for metagenomic samples with a very high fraction of non-target reads (> 99% can be human reads). Read-until, however, requires a fast and accurate software filter that analyzes a short prefix of a read and determines if it belongs to a microbe of interest (target) or not. The baseline Read Until pipeline uses a deep neural network-based basecaller called Guppy and is slow and inaccurate for this task (60% of bases sequenced are unclassified). We present RawMap, an efficient CPU-only microbial species-agnostic Read Until classifier for filtering non-target human reads in the squiggle space. RawMap uses a Support Vector Machine (SVM), which is trained to distinguish human from microbe using non-linear and non-stationary characteristics of ONT’s squiggle output (continuous electrical signals). Compared to the baseline Read Until pipeline, RawMap is 1327X faster and significantly improve the sequencing time and cost, and compute time savings. We show that RawMap augmented pipelines reduce sequencing time and cost by 23.79% and computing cost by 22%. Additionally, since RawMap is agnostic to microbial species, it can also classify microbial species it is not trained on. We also discuss how RawMap may be used as an alternative to the RT-PCR test for viral load quantification of SARS-CoV-2.
  🖺 Full Text HTML: Rapid Real-time Squiggle Classification for Read Until Using RawMap
• Fragment-Based Hit Discovery via Unsupervised Learning of Fragment-Protein Complexes -
  The process of finding molecules that bind to a target protein is a challenging first step in drug discovery. Crystallographic fragment screening is a strategy based on elucidating binding modes of small polar compounds and then building potency by expanding or merging them. Recent advances in high-throughput crystallography enable screening of large fragment libraries, reading out dense ensembles of fragments spanning the binding site. However, fragments typically have low affinity thus the road to potency is often long and fraught with false starts. Here, we take advantage of high-throughput crystallography to reframe fragment-based hit discovery as a denoising problem – identifying significant pharmacophore distributions from a fragment ensemble amid noise due to weak binders – and employ an unsupervised machine learning method to tackle this problem. Our method screens potential molecules by evaluating whether they recapitulate those fragment-derived pharmacophore distributions. We retrospectively validated our approach on an open science campaign against SARS-CoV-2 main protease (Mpro), showing that our method can distinguish active compounds from inactive ones using only structural data of fragment-protein complexes, without any activity data. Further, we prospectively found novel hits for Mpro and the Mac1 domain of SARS-CoV-2 non-structural protein 3. More broadly, our results demonstrate how unsupervised machine learning helps interpret high throughput crystallography data to rapidly discover of potent chemical modulators of protein function.
  🖺 Full Text HTML: Fragment-Based Hit Discovery via Unsupervised Learning of Fragment-Protein Complexes
• RE2DC: a robust and efficient 2D classifier with visualization for processing massive and heterogeneous cryo-EM data -
  Despite the fact that single particle cryo-EM has become a powerful method of structural biology, processing cryo-EM images are challenging due to the low SNR, high-dimension and un-label nature of the data. Selecting the best subset of particle images relies on 2D classification - a process that involves iterative image alignment and clustering. This process, however, represents a major time sink, particularly when the data is massive or overly heterogeneous. Popular approaches to this process often trade its robustness for efficiency. Here, we introduced a new unsupervised 2D classification method termed RE2DC. It is built upon a highly efficient variant of {gamma}-SUP, a robust statistical cryo-EM clustering algorithm resistant to the attractor effect. To develop this efficient variant, we employed a tree-based approximation to reduce the computation complexity from O(N2) to O(N), with N as the number of images. In addition, we exploited t-SNE visualization to unveil the process of 2D classification. Our tests of RE2DC using various datasets demonstrate it is both robust and efficient, with the potential to reveal subtle structural intermediates. Using RE2DC to curate a dataset of sub-millions of COVID-19 spike particles picked from 3,511 movies only takes 8 hours, suggesting its capability of accelerating cryo-EM structural determination. Currently, RE2DC is available with both CPU and GPU versions, where the implementation only requires modest hardware resources.
  🖺 Full Text HTML: RE2DC: a robust and efficient 2D classifier with visualization for processing massive and heterogeneous cryo-EM data
• Feline Coronavirus Infection of Domestic Cats Causes Development of Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain -
  The current study was initiated when our specific pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each from FCoV serotypes 1 and 2 (FCoV1, FCoV2) demonstrated amino acid sequence identity of 11.5% and similarity of 31.8% with FCoV1 RBD, as well as 12.2% identity and 36.5% similarity for FCoV2 RBD. The sera from all three toms and three mated queens cross-reacted with SCoV2 RBD and reacted with FCoV1 RBD and FCoV2 spike-2, nucleocapsid, and membrane proteins of FCoV2 whole-virus, but not with FCoV2 RBD. Additionally, the plasma from all six FCoV2-inoculated laboratory cats reacted with FCoV2 and SCoV2 RBDs, but not with FCoV1 RBD. In another study, eight group-housed laboratory cats from a different lineage had a range of serum cross-reactivity to SCoV2 RBD even 15 months later. Such cross-reactivity was also observed in FCoV1-positive group-housed pet cats. The SCoV2 RBD at a high non-toxic dose and FCoV2 RBD at a 60-400-fold lower dose blocked the in vitro FCoV2 infection of the feline cells, demonstrating their close structural conformations essential as vaccine immunogens. Furthermore, such cross-reactivity to SCoV2 RBD was also detected by the peripheral blood mononuclear cells of both transient and chronically FCoV1-infected cats. Overall, the cross-reactivity with SCoV2 RBD by the sera from both serotypes of FCoV-infected cats also suggests that the cross-reactive epitope(s) on FCoV1 and FCoV2 RBDs may be similar to those of SCoV2 RBD and provides essential insights to developing a pan-CoV vaccine.
  🖺 Full Text HTML: Feline Coronavirus Infection of Domestic Cats Causes Development of Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain
• Trajectories of Relationship and Sexual Satisfaction Over Two Years in the Covid-19 Pandemic -
  The impact of the Covid-19 pandemic on various aspects of life, including romantic relationships, has already been demonstrated in several investigations. The aim of the present study was to extend these findings by including a period extending from the beginning to the near end of the pandemic (April 2020-March 2022) and applying a latent class approach to identify population subgroups with different relationship and sexual satisfaction trajectories. We identified three latent classes, a group with high satisfaction levels but a descending trajectory, a group with low satisfaction levels but an ascending trajectory, and a fluctuating group. Living apart, psychological symptoms, low life satisfaction, and avoidant attachment characterized the latter two groups. Separations were mainly predicted by sex and living apart.
  🖺 Full Text HTML: Trajectories of Relationship and Sexual Satisfaction Over Two Years in the Covid-19 Pandemic
• Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses -
  Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.
  🖺 Full Text HTML: Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses
• Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus -
  There is an urgent need for efficient and safe vaccines against the monkeypox virus (MPXV) in response to the rapidly spreading monkeypox epidemic. In the age of COVID-19, mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation. Here, we have developed two MPXV quadrivalent mRNA vaccines, named mRNA-A-LNP and mRNA-B-LNP, based on two IMVs (A29L and M1R) and two EEVs (A35R and B6R). By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice, mice have induced MPXV-specific IgG antibodies and potent Vaccinia virus (VACV)-specific neutralizing antibodies. Additionally, it elicited durable MPXV-specific killer memory T-cell immunity as well as memory B-cell immunity in mice. Furthermore, the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protected nude mice against the VACV challenge. In addition, two doses of mRNA-A-LNP and mRNA-B-LNP were also protective against the VACV challenge in mice. Overall, our results demonstrated that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics, as well as against outbreaks caused by other orthopoxviruses, including the smallpox virus.
  🖺 Full Text HTML: Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus
• Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein -
  SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging showed that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Strikingly, cellular cryo-electron tomography revealed dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and found that S protein recognizes integrin v{beta}3. Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.
  🖺 Full Text HTML: Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein

From Clinical Trials

• A Study on Voluntary Routine COVID-19 Self-testing in Mizoram, India. - Condition:   COVID-19
  Intervention:   Diagnostic Test: COVID-19 Self testing and related messaging
  Sponsors:   PATH;   UNITAID;   Zoram Medical College (ZMC);   Pacchunga University College;   Association for Leprosy Education Rehabilitation & Treatment India (ALERT India);   Government of Mizoram
  Not yet recruiting

• A Study to Evaluate EDP-235 in Non-hospitalized Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: EDP-235;   Drug: Placebo
  Sponsor:   Enanta Pharmaceuticals, Inc
  Recruiting

• Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: RAY1216;   Drug: Placebo
  Sponsor:   Guangdong Raynovent Biotech Co., Ltd
  Not yet recruiting

• The LAVA (Lateral Flow Antigen Validation and Applicability) 2 Study for COVID-19 - Condition:   SARS-CoV-2 Infection
  Intervention:   Diagnostic Test: Innova Lateral Flow Test
  Sponsor:   Alder Hey Children’s NHS Foundation Trust
  Completed

• Q-POC SARS-CoV-2 Assay COVID-19 Clinical Evaluation - Condition:   COVID-19
  Interventions:   Diagnostic Test: RT-PCR Test;   Diagnostic Test: Real-time PCR Test
  Sponsors:   QuantuMDx Group Ltd;   EDP Biotech;   Paragon Rx Clinical;   PathAI;   PRX Research and Development
  Not yet recruiting

• Acute Rehabilitation in Patients With COVID-19 Pneumonia - Conditions:   COVID-19;   Rehabilitation;   Physical Medicine
  Intervention:   Procedure: Acute rehabilitation program
  Sponsor:   Institut za Rehabilitaciju Sokobanjska Beograd
  Recruiting

• Enhancing Protection Against Influenza and COVID-19 for Pregnant Women and Medically at Risk Children - Conditions:   Influenza;   COVID-19
  Intervention:   Behavioral: Nudge
  Sponsor:   University of Adelaide
  Recruiting

• A Trial Evaluate the Immunogenicity and Safety of Recombinant COVID-19 Omicron-Delta Variant Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Omicron-Delta Recombinant Novel Coronavirus Protein Vaccine (CHO cells);   Biological: Recombinant Novel Coronavirus Protein Vaccine (CHO cells)
  Sponsor:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
  Recruiting

• COVID-19 Antibody Responses in Cystic Fibrosis - Conditions:   COVID-19;   Cystic Fibrosis
  Intervention:   Biological: Blood sample
  Sponsors:   Hospices Civils de Lyon;   Queen’s University, Belfast
  Recruiting

• Message Communicating Latest Data on COVID Transmission in Patient’s Area - Condition:   COVID-19
  Intervention:   Behavioral: COVID Booster text messages
  Sponsor:   University of Pennsylvania
  Enrolling by invitation

• Message From Local Pharmacy Team - Condition:   COVID-19
  Intervention:   Behavioral: COVID Booster text messages
  Sponsor:   University of Pennsylvania
  Enrolling by invitation

• Safety, Tolerability, and Immunogenicity of Trivalent Coronavirus Vaccine Candidate VBI-2901e With E6020 Adjuvant - Conditions:   COVID-19;   Coronavirus Infections
  Intervention:   Biological: VBI-2901e
  Sponsor:   VBI Vaccines Inc.
  Not yet recruiting

• Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection - Conditions:   Health Behavior;   Child Development;   Adolescent Obesity
  Interventions:   Dietary Supplement: Probiotics;   Behavioral: Counselling on healthy eating, physical activity, and psychosocial stimulation;   Dietary Supplement: Placebo probiotics
  Sponsors:   Indonesia University;   Gadjah Mada University;   Universitas Airlangga;   University of Melbourne;   The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia
  Recruiting

• Phonation Therapy to Improve Symptoms and Lung Physiology in Patients Referred for Pulmonary Rehabilitation - Condition:   COVID-19
  Interventions:   Behavioral: Tonation Breathing Techniques;   Behavioral: Music Driven Vocal Exercises;   Behavioral: Silent Breathing
  Sponsor:   MetroHealth Medical Center
  Recruiting

• Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings - Condition:   COVID-19
  Interventions:   Drug: Paxlovid;   Drug: Other;   Other: Other
  Sponsors:   Unity Health Toronto;   Canadian Institutes of Health Research (CIHR);   Health Canada
  Not yet recruiting

From PubMed

• Treatment of Advanced Systemic Mastocytosis with Midostaurin: Practical Guidance for Optimal Therapy and Management - Systemic mastocytosis (SM) is a rare disease with a range of clinical presentations, and the vast majority of patients have a KIT D816V mutation that results in a gain of function. The multikinase/KIT inhibitor midostaurin inhibits the D816V mutant and has a well-established role in treating advanced SM. Even if considered the standard of therapy, some open questions remain on optimizing midostaurin management in daily practice. The current review presents the opinions of a group of experts who…

• Computational search for potential COVID-19 drugs from ayurvedic medicinal plants to identify potential inhibitors against SARS-CoV-2 targets - CONCLUSION: Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike protein of SARS-CoV-2.

• CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis - COVID-19 patients can develop clinical and histopathological features associated with fibrosis, but the pathogenesis of fibrosis remains poorly understood. CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants, which could initiate COVID-19-related cytokine storm. Here, we systemically analyzed lung pathogenesis in SARS-CoV-2- and its delta variant-infected humanized CD147 transgenic mice. Histopathology and Transmission Electron Microscopy revealed inflammation,…

• Rational Design and Synthesis of D-galactosyl Lysophospholipids as Selective Substrates and non-ATP-competitive Inhibitors of Phosphatidylinositol Phosphate Kinases - Phosphatidylinositol phosphate kinases (PIPKs) produce lipid signaling molecules and have been attracting increasing attention as drug targets for cancer, neurodegenerative diseases, and viral infection. Given the potential cross-inhibition of kinases and other ATP-utilizing enzymes by ATP-competitive inhibitors, targeting the unique lipid substrate binding site represents a superior strategy for PIPK inhibition. Here, by taking advantage of the nearly identical stereochemistry between…

• Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier - SARS-CoV-2 is the causative agent of the immune response-driven disease COVID-19 for which new antiviral and anti-inflammatory treatments are urgently needed to reduce recovery time, risk of death and long COVID development. Here, we demonstrate that the immunoregulatory kinase p38 MAPK is activated during viral entry, mediated by the viral spike protein, and drives the harmful virus-induced inflammatory responses. Using primary human lung explants and lung epithelial organoids, we demonstrate…

• Nanobody derived using a peptide epitope from the Spike protein receptor-binding motif inhibits entry of SARS-CoV-2 variants - The emergence of new escape mutants of the SARS-CoV-2 virus has escalated its penetration among the human population and has reinstated its status as a global pandemic. Therefore, developing effective antiviral therapy against emerging SARS-CoV variants and other viruses in a short period of time becomes essential. Blocking SARS-CoV-2 entry into human host cells by disrupting the Spike glycoprotein-angiotensin-converting enzyme 2 (ACE2) interaction has already been exploited for vaccine…

• Xuanfei Baidu formula alleviates impaired mitochondrial dynamics and activated NLRP3 inflammasome by repressing NF-κB and MAPK pathways in LPS-induced ALI and inflammation models - CONCLUSION: In this study, we demonstrate that XBF exerts anti-ALI and -inflammatory effects by recovering mitochondrial dynamics and reducing inflammasome activation, providing a biological illustration of the clinical efficacy of XBF in treating COVID-19 patients.

• Computational investigation of natural compounds as potential main protease (M^pro) inhibitors for SARS-CoV-2 virus - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significantly impacting human lives, overburdening the healthcare system and weakening global economies. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. The SARS-CoV-2 Main protease (M^(pro)) is considered an appealing target because of its role in replication in host cells. We curated a set…

• IFITM3 Inhibits SARS-CoV-2 Infection and Is Associated with COVID-19 Susceptibility - SARS-CoV-2 has become a global threat to public health. Infected individuals can be asymptomatic or develop mild to severe symptoms, including pneumonia, respiratory distress, and death. This wide spectrum of clinical presentations of SARS-CoV-2 infection is believed in part due to the polymorphisms of key genetic factors in the population. In this study, we report that the interferon-induced antiviral factor IFITM3 inhibits SARS-CoV-2 infection by preventing SARS-CoV-2 spike-protein-mediated…

• Prevention and Treatment of Monkeypox: A Systematic Review of Preclinical Studies - The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as…

• Antiviral activity of nano-monocaprin against Phi6 as a surrogate for SARS-CoV-2 - The COVID-19 pandemic involving SARS-CoV-2 has raised interest in using antimicrobial lipid formulations to inhibit viral entry into their host cells or to inactivate them. Lipids are a part of the innate defense mechanism against pathogens. Here, we evaluated the use of nano-monocaprin (NMC) in inhibiting enveloped (phi6) and unenveloped (MS2) bacteriophages. NMC was prepared using the sonochemistry technique. Size and morphology analysis revealed the formation of ~ 8.4 ± 0.2-nm NMC as measured…

• Antiviral Properties of Pennisetum purpureum Extract against Coronaviruses and Enteroviruses - Many severe epidemics are caused by enteroviruses (EVs) and coronaviruses (CoVs), including feline coronavirus (FCoV) in cats, epidemic diarrhea disease virus (PEDV) in pigs, infectious bronchitis virus (IBV) in chickens, and EV71 in human. Vaccines and antiviral drugs are used to prevent and treat the infection of EVs and CoVs, but the effectiveness is affected due to rapidly changing RNA viruses. Many plant extracts have been proven to have antiviral properties despite the continuous mutations…

• Investigating the Potential Anti-SARS-CoV-2 and Anti-MERS-CoV Activities of Yellow Necklacepod among Three Selected Medicinal Plants: Extraction, Isolation, Identification, In Vitro, Modes of Action, and Molecular Docking Studies - The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5% and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2…

• Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs - Gold compounds have a long tradition in medicine and offer many opportunities for new therapeutic applications. Herein, we evaluated the lead compound Auranofin and five related gold(I) complexes as possible inhibitors of SARS-CoV-2 Main Protease (SARS-CoV-2 M^(pro)), a validated drug target for the COVID-19 disease. The investigational panel of gold compounds included Auranofin; three halido analogues, i.e., Au(PEt(3))Cl, Au(PEt(3))Br, and Au(PEt(3))I; and two gold carbene complexes, i.e.,…

• Inhibition of SARS-CoV-2 Viral Channel Activity Using FDA-Approved Channel Modulators Independent of Variants - CONCLUSIONS: We developed an efficient method to screen FDA-approved ion channel modulators that could be repurposed to detect and inhibit SARS-CoV-2 viral replication, independent of variants.

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