Covid-19 Sentry

Contents

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

From Preprints

• Erythromycin, Retapamulin, Pyridoxine, Folic acid, and Ivermectin dose-dependently inhibit cytopathic effect, Papain-like Protease, and MPRO of SARS-CoV-2 -
  We previously showed that Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin inhibit SARS-COV-2 induced cytopathic effect (CPE) in Vero cells. In this study and using validated quantitative neutral red assay, we show that the inhibition of CPE is concentration dependent with Inhibitory Concentration-50(IC50) of 3.27 microM, 4.23 microM, 9.29 microM, 3.19 microM and 84.31 microM respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50 of 0.94 microM, 0.88 microM, 1.14 microM, 1.07 microM, 1.51 microM respectively and the main protease(MPRO) with IC50 of 1.35 microM, 1.25 microM, 7.36 microM, 1.15 microM, and 2.44 microM respectively. The IC50 for all the drugs, except ivermectin, are at the clinically achievable plasma concentration in human, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by Ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.
  🖺 Full Text HTML: Erythromycin, Retapamulin, Pyridoxine, Folic acid, and Ivermectin dose-dependently inhibit cytopathic effect, Papain-like Protease, and MPRO of SARS-CoV-2
• SARS-CoV-2 accessory proteins ORF3a and ORF7a modulate autophagic flux and Ca2+ homeostasis in yeast -
  Virus infection involves the manipulation of key host cell functions by specialized virulence proteins. The SARS-CoV-2 small accessory proteins ORF3a and ORF7a have been implicated in favoring virus replication and spreading by inhibiting the autophagic flux within the host cell. Here, we apply yeast models to gain insights into the physiological functions of both SARS-CoV-2 small ORFs. ORF3a and ORF7a can be stably overexpressed in yeast cells, producing a decrease in cellular fitness. Both proteins show a distinguishable intracellular localization. ORF3a specifically localizes to the vacuolar membrane, whereas ORF7a targets the endoplasmic reticulum. Overexpression of ORF3a and ORF7a leads to the accumulation of Atg8 specific autophagosomes. However, the underlying mechanism is different for each viral protein as assessed by the quantification of the autophagic degradation of Atg8-GFP fusion proteins, which is inhibited by ORF3a and stimulated by ORF7a. Overexpression of both SARS-CoV-2 ORFs decreases cellular fitness upon starvation conditions, where autophagic processes become essential. These data are in agreement with a model where both small ORFs have synergistic functions in stimulating intracellular autophagosome accumulation, ORF3a by inhibiting autophagosome processing at the vacuole and ORF7a by promoting autophagosome formation at the ER. ORF3a has an additional function in Ca2+ homeostasis. The overexpression of ORF3a confers calcineurin-dependent Ca2+ tolerance and activates a Ca2+ sensitive FKS2-luciferase reporter, suggesting a possible ORF3a-mediated Ca2+ efflux from the vacuole. Taken together, we show that viral accessory proteins can be functionally investigated in yeast cells and that SARS-CoV-2 ORF3a and ORF7a proteins interfere with autophagosome formation and processing as well as with Ca2+ homeostasis from distinct cellular targets.
  🖺 Full Text HTML: SARS-CoV-2 accessory proteins ORF3a and ORF7a modulate autophagic flux and Ca2+ homeostasis in yeast
• Immunogenicity of COVID-eVax Is Moderately Impacted by Temperature and Molecular Isoforms -
  DNA integrity is a key issue in gene therapy and genetic vaccine approaches based on plasmid DNA. In contrast to messenger RNA that requires a controlled cold chain for efficacy, DNA molecules are considered to be more stable. In this study, we challenged this concept by characterizing the immunological response induced by a plasmid DNA vaccine delivered using electroporation. As a model, we used COVID-eVax, which is a plasmid DNA vaccine that targets the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Increased nicked DNA was produced by using either an accelerated stability protocol or a lyophilization protocol. Surprisingly, the immune response induced in vivo was only minimally affected by the percentage of open circular DNA. This result suggests that plasmid DNA vaccines, such as COVID-eVax that has completed a phase I clinical trial, retain their efficacy upon storage at higher temperatures and this feature may facilitate their use in low-/middle-income countries.
  🖺 Full Text HTML: Immunogenicity of COVID-eVax Is Moderately Impacted by Temperature and Molecular Isoforms
• A robust deep learning platform to predict CD8+ T-cell epitopes -
  T-cells play a crucial role in the adaptive immune system by inducing an anti-tumour response, defending against pathogens, and maintaining tolerance against self-antigens, which has sparked interest in the development of T-cell-based vaccines and immunotherapies. Because screening antigens driving the T-cell response is currently low-throughput and laborious, computational methods for predicting CD8+ T-cell epitopes have emerged. However, most immunogenicity algorithms struggle to learn features of peptide immunogenicity from small datasets, suffer from HLA bias and are unable to reliably predict pathology-specific CD8+ T-cell epitopes. Therefore, we developed TRAP (T-cell recognition potential of HLA-I presented peptides), a robust deep learning platform for predicting CD8+ T-cell epitopes from MHC-I presented pathogenic and self-peptides. TRAP uses transfer learning, deep learning architecture and MHC binding information to make context-specific predictions of CD8+ T-cell epitopes. TRAP also detects low-confidence predictions for peptides that differ significantly from those in the training datasets to abstain from making incorrect predictions. To estimate the immunogenicity of pathogenic peptides with low-confidence predictions, we further developed a novel metric, RSAT (relative similarity to autoantigens and tumour-associated antigens), as a complementary to dissimilarity to self from cancer studies. We used TRAP to identify epitopes from glioblastoma patients as well as SARS-CoV-2 peptides, and it outperformed other algorithms in both cancer and pathogenic settings. Thus, this study presents a novel computational platform for accurately predicting CD8+ T-cell epitopes to foster a better understanding of antigen-specific T-cell response and the development of effective clinical therapeutics.
  🖺 Full Text HTML: A robust deep learning platform to predict CD8+ T-cell epitopes
• Maternal Mortality within the African American Population in the United States -
  This paper discusses the prominence of maternal mortality among the African American population in the United States. Statistics regarding the state of the maternal mortality crisis are listed, as well as how the United States compares to other first-world countries. Trends that have resulted in the crisis are discussed, as well as how they have changed over time. The effect of COVID-19 on maternal complications and the crisis are described. Lastly, there is a focus on the factors that have contributed and continue to contribute to this phenomenon, as well as potential solutions.
  🖺 Full Text HTML: Maternal Mortality within the African American Population in the United States
• New compartment model for COVID-19 -

  Population is separated into five compartments for COVID-19; susceptible individuals (S), pre-symptomatic patients (P), asymptomatic patients (A), quarantined patients (Q) and recovered and/or dead patients (R). The time evolution of each compartment is described by a set of ordinary differential equations. Numerical solution to the set of differential equations shows that quarantining pre-symptomatic and asymptomatic patients is effective in controlling the pandemic. It is also shown that the ratio of non-symptomatic patients to the daily confirmed new cases can be as large as 20 and that the fraction of untraceable cases in new cases can be as large as 80%, depending on the policies for social distancing and PCR test.

  🖺 Full Text HTML: New compartment model for COVID-19
• Intranasal inhibitor broadly blocks SARS-CoV-2 including recent highly immunoevasive Omicron subvariants -
  The recent emergence of novel SARS-CoV-2 variants capable of efficiently escaping neutralizing antibodies emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Nasal epithelium is rich in the ACE2 receptor and important for SARS-CoV-2 transmission by supporting early viral replication before seeding to the lung. Intranasal administration of SARS-CoV-2 neutralizing antibodies or antibody fragments has shown encouraging potential as a protective measure in animal models. However, there remains a dire need for SARS-CoV-2 blocking agents that are less vulnerable to mutational variation in the neutralization epitopes of the viral spike glycoprotein and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and extremely stable trimeric human SH3 domain-derived antibody mimetic targeted against a conserved region in the receptor-binding domain of spike. TriSb92 potently neutralizes SARS-CoV-2 and its variants of concern, including Omicron BA.5 as well as the latest and most immunoevasive variants like BF.7, XBB, and BQ.1.1. Intranasal administration of a modest dose of TriSb92 (5 or 50 micrograms) as early as eight hours before a challenge with SARS-CoV-2 efficiently protected mice from infection, and was still effective even when given 4 h after the viral challenge. The target epitope of TriSb92 was defined by cryo-EM, which revealed triggering of a conformational shift in the spike trimer rather than competition for ACE2 binding as the molecular basis of its strong inhibitory action. The high potency and robust biochemical properties of TriSb92 together with the remarkable resistance of its inhibitory action against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.
  🖺 Full Text HTML: Intranasal inhibitor broadly blocks SARS-CoV-2 including recent highly immunoevasive Omicron subvariants
• The Effect of COVID-19 on Distracted Driving: A Survey Study -

  The COVID-19 pandemic caused a significant shift in people9s travel behaviors and distractions while driving. This paper aims to investigate the impacts of the COVID-19 pandemic on distracted driving by comparing their behavior before and during the pandemic (from 3/1/2019 to 3/1/2021) in the state of Maryland using a stated preference online survey. Some 158 people were recruited for the survey. Participants were asked about their risky driving behaviors and self-reported distraction both before and during the pandemic. To analyze the results, the Chi-square and post-hoc tests with the Bonferroni adjustment were applied. The results showed that during the pandemic, distraction dropped from 25% to 21%. The highest reported distracted driving behavior during the pandemic was using hands-free cell phones (64%), using GPS (75%), and eating or drinking (57%). The respondents9 daily trips have significantly decreased - about 44% below pre-pandemic rates. Moreover, using a binary logistic regression, it was revealed that the odds of becoming distracted among participants who used a handheld cell phone before and during the pandemic were 4.5 and 6.6 times higher than others, respectively. The findings of this study shed light on the causes of distraction before and during the pandemic.

  🖺 Full Text HTML: The Effect of COVID-19 on Distracted Driving: A Survey Study
• Estimating the transmission dynamics of Omicron in Beijing, November to December 2022 -

  We tracked the effective reproduction number Rt of SARS-CoV-2 Omicron BF.7 in Beijing in November-December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on November 1-11 (when the zero-covid interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on December 10-22 and self-reported to have been previously test-positive since November 1. After the announcement of “20 measures”, we estimated that Rt increased to 3.44 (95% CrI: 2.82-4.14) on November 18 and the infection incidence peaked on December 11. The cumulative infection attack rate (i.e. the proportion of population who have been infected since November 1) was 43.1% (95% CrI: 25.6-60.9) on December 14 and 75.7% (95% CrI: 60.7-84.4) on December 22. Surveillance programmes should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.

  🖺 Full Text HTML: Estimating the transmission dynamics of Omicron in Beijing, November to December 2022
• Viral and host small RNA transcriptome analysis of SARS-CoV-1 and SARS-CoV-2-infected human cells reveals novel viral short RNAs. -
  RNA viruses have been shown to express various short RNAs, some of which have regulatory roles during replication, transcription, and translation of viral genomes. However, short viral RNAs (svRNAs) generated by SARS-CoV-1 and SARS-CoV-2 remained largely unexplored, mainly due limitations of the widely used library preparation methods for small RNA deep sequencing and corresponding data processing. By analyzing publicly available small RNA-seq datasets, we observed that human cells infected by SARS-CoV-1 or SARS-CoV-2 produce multiple short viral RNAs (svRNAs), ranging in size from 15 to 26 nt and deriving predominantly from (+) RNA strands. In addition, we verified the presence of the five most abundant SARS-CoV-2 svRNAs in SARS-CoV-2-infected human lung adenocarcinoma cells by qPCR. Interestingly, the copy number of the observed SARS-CoV-2 svRNAs dramatically exceeded the expression of previously reported viral miRNAs in the same cells. We hypothesize that the reported SARS-CoV-2 svRNAs could serve as biomarkers for early infection stages due to their high abundance. Finally, we found that both SARS-CoV-1 and SARS-CoV-2 infection induced up- and down-regulation of multiple endogenous human short RNAs that align predominantly to protein-coding and lncRNA transcripts. Interestingly, a significant proportion of short RNAs derived from full-length viral genomes also aligned to various hg38 sequences, suggesting opportunities to investigate regulatory roles of svRNAs during infection. Further characterization of the small RNA landscape of both viral and host genomes is clearly warranted to improve our understanding of molecular events related to infection and to design more efficient strategies for therapeutic interventions as well as early diagnosis.
  🖺 Full Text HTML: Viral and host small RNA transcriptome analysis of SARS-CoV-1 and SARS-CoV-2-infected human cells reveals novel viral short RNAs.
• SCIP: A self-paced, community-based summer coding program creates community and increases coding confidence -
  In 2020, many students lost summer opportunities due to the COVID-19 pandemic. We wanted to offer students an opportunity to learn computational skills and be part of a community while stuck at home. Because the pandemic created an unexpected research and academic situation, it was unclear how to best support students to learn and build community online. We used lessons learned from literature and our own experience to design, run and test an online program for students called the Science Coding Immersion Program (SCIP). In our program, students worked in teams for 8 hours a week, with one participant as the team leader and Zoom host. Teams worked on an online R or Python class at their own pace with support on Slack from the organizing team. For motivation and career advice, we hosted a weekly webinar with guest speakers. We used pre- and post-program surveys to determine how different aspects of the program impacted students. We were able to recruit a large and diverse group of participants who were happy with the program, found community in their team, and improved their coding confidence. We hope that our work will inspire others to start their own version of SCIP.
  🖺 Full Text HTML: SCIP: A self-paced, community-based summer coding program creates community and increases coding confidence
• A second update on mapping the human genetic architecture of COVID-19 -

  Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release. The increased number of candidate genes at the identified loci helped to map three major biological pathways involved in susceptibility and severity: viral entry, airway defense in mucus, and type I interferon.

  🖺 Full Text HTML: A second update on mapping the human genetic architecture of COVID-19
• Study COVID-19 Severity of Patients Admitted to Emergency Room (ER) with Chest X-ray Images -

  Abstract. We have conducted a study of the COVID-19 severity with the chest x-ray images, a private dataset collected from our collaborator St Bernards Medical Center. The dataset is comprised of chest x-ray images from 1,550 patients who were admitted to emergency room (ER) and were all tested positive for COVID-19. Our study is focused on the following two questions: (1) To predict patients hospital staying duration, based on the chest x-ray image which was taken when the patient was admitted to the ER. The length of stay ranged from zero hours to 95 days in the hospital and followed a power law distribution. Based on our testing results, it is hard for the prediction models to detect strong signal from the chest x-ray images. No model was able to perform better than a trivial most-frequent classifier. However, each model was able to outperform the most-frequent classifier when the data was split evenly into four categories. This would suggest that there is signal in the images, and the performance may be further improved by the addition of clinical features as well as increasing the training set. (2) To predict if a patient is COVID-19 positive or not with the chest x-ray image. We also tested the generalizability of training a prediction model on chest x-ray images from one hospital and then testing the model on images captures from other sites. With our private dataset and the COVIDx dataset, the prediction model can achieve a high accuracy of 95.9%. However, for our hold-one-out study of the generalizability of the models trained on chest x-rays, we found that the model performance suffers due to a significant reduction in training samples of any class.

  🖺 Full Text HTML: Study COVID-19 Severity of Patients Admitted to Emergency Room (ER) with Chest X-ray Images
• Literature analysis of the efficacy of COVID-19 vaccinations -

  The COVID-19 pandemic is the largest epidemic of the 21st century so far. Over 650 million people have already been infected with the SARS-CoV-2 virus. One of the ways to stop this pandemic, is to vaccinate the population and gain herd immunity. Many different vaccines are being used around the world, with differing efficacy. This review summarizes the 79 publications on the efficacy of the currently existing COVID-19 vaccines. It shows that there are eleven vaccines that have efficacy data published in a PubMed-indexed scientific journal. Most research has been done on the Pfizer/BioNTech BNT162B2 vaccine, and the eleven vaccines generally have a high efficacy in preventing illness. The Pfizer (86%-100%), Moderna (93.2%-94.1%), Sputnik-V (91.6%) and Novavax (~90%) vaccines show the highest efficacy, followed by the Sinovac (83.5%), QazCovid-in 82%) and Covaxin (77.8%) vaccines. The Oxford/AstraZeneca (69% - 81.5%) and Johnson & Johnson (66%) vaccines have lower efficacy in preventing illness. This overview also shows efficacies other than in preventing illness (e.g. asymptomatic, severe illness, hospitalization, death) in some cases. The results also show that the vaccines have specific effects on specific age groups (e.g. adolescents, adults, elderly) and people with diseases (e.g. leukemia, other cancers, HIV). Future research in this area will mostly focus on vaccine efficacy on specific strains of the SARS-CoV-2 virus (such as the Omicron variant) as well as the efficacy of booster vaccinations.

  🖺 Full Text HTML: Literature analysis of the efficacy of COVID-19 vaccinations
• A Usability Evaluation of YouDiagnose: Artificial Intelligence Powered Physician Consultation -

  The COVID-19 Pandemic has resulted in a forced transition to telemedicine, where history-taking and clinical assessments are performed remotely during video or telephonic consultations. While telemedicine has added to safety and social distancing during the pandemic, the manual and resource-intense pro-cess of telephonic and video consultations has not helped to ease the patient backlog, rather has added to this snowballing issue. This paper describes about YouDiagnose pre-consultation exercise that automates patient triage and clinical assessment using artificial intelligence technologies delivered through either a Smart Questionnaire or Chatbot. A usability evaluation was conducted with participants from the Patient and Public Involvement and Engagement Senate (PIES) of the Innovation Agency (an Academic Health Science Net-work) Qualitative feedback was obtained from the participants on both modalities and quantitative feedback in the form of the System Usability Scale (SUS), comparing the usability of both interaction modalities. The SUS scores were analysed using the Adjective Rating Scale that revealed the Smart Questionnaire had Good Usability compared to OK Usability of the Chatbot. The results shows the user experience and untapped potential of process automation and artificial intelligence in clinical services.

  🖺 Full Text HTML: A Usability Evaluation of YouDiagnose: Artificial Intelligence Powered Physician Consultation

From Clinical Trials

• 101-PGC-005 for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: 101-PGC-005;   Drug: Dexamethasone
  Sponsor:   101 Therapeutics
  Recruiting

• A Clinical Study to Assess Preliminary Efficacy, Safety and Tolerability of HH-120 Nasal Spray in COVID-19 Patients - Condition:   Coronavirus Disease 2019(COVID-19)
  Intervention:   Biological: HH-120 Nasal Spray
  Sponsor:   Beijing Ditan Hospital
  Recruiting

• COVID-19 Booster Study in Healthy Adults in Australia - Condition:   COVID-19
  Interventions:   Biological: Bivalent Moderna;   Biological: Novavax
  Sponsors:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   The Peter Doherty Institute for Infection and Immunity
  Not yet recruiting

• Effect of N-Acetylcysteine on Neutrophil Lymphocyte Ratio And Length of Stay In COVID-19 Patients - Condition:   COVID-19
  Intervention:   Drug: N-acetyl cysteine
  Sponsor:   Universitas Sebelas Maret
  Completed

• Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People - Condition:   COVID-19
  Interventions:   Drug: SA58 Nasal Spray;   Drug: Placebo
  Sponsors:   Sinovac Life Sciences Co., Ltd.;   Beijing Ditan Hospital
  Recruiting

• Efficacy and Safety of Anti-COVID-19 Antibody SA58 Nasal Spray to Prevent Infection in High-risk Populations - Condition:   COVID-19
  Intervention:   Drug: SA58 Nasal Spray
  Sponsor:   Sinovac Life Sciences Co., Ltd.
  Recruiting

• Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: One dose group;   Biological: Two doses group;   Biological: Aged 18-59 years;   Biological: Aged 60 years old and above
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.
  Not yet recruiting

• Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly;   Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled;   Drug: Standard of care
  Sponsor:   Promomed, LLC
  Completed

• Immunogenicity and Safety of COVID-19 Vaccine as a Booster Vaccination in Population Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Vaccine (CHO Cell) LYB001;   Biological: ZF2001
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.
  Not yet recruiting

• Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: CoronaVac/CoronaVac;   Biological: CoronaVac/BNT162b2
  Sponsor:   Institut Pasteur de Tunis
  Completed

• Study of GST-HG171/Ritonavir Compared With Placebo in Patients With Mild to Moderate COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: GST-HG171/Ritonavir;   Drug: Placebo
  Sponsor:   Fujian Akeylink Biotechnology Co., Ltd.
  Not yet recruiting

• The COPE Study: Pilot Intervention to Improve Symptom Self-management and Coping in Adults With Post COVID-19 - Conditions:   Post COVID-19 Condition;   Post-COVID-19 Syndrome
  Intervention:   Behavioral: 6-Week Self-Management Group
  Sponsor:   University of Washington
  Not yet recruiting

• ICBT for Psychological Symptoms Related to the COVID-19 Pandemic Remaining After Societal Opening - Condition:   Depression and Anxiety Symptoms Related to the COVID-19 Pandemic
  Intervention:   Behavioral: Internet-based Cognitive Behavioral Therapy
  Sponsor:   Linkoeping University
  Not yet recruiting

• ARVAC - A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine - Condition:   COVID-19 Vaccine
  Intervention:   Biological: ARVAC-CG vaccine (recombinant protein vaccine against SARS-CoV-2)
  Sponsors:   Laboratorio Pablo Cassara S.R.L.;   Universidad Nacional de San Martín (UNSAM);   National Council of Scientific and Technical Research, Argentina
  Active, not recruiting

• The KIN-FAST Trial (KIN001 For Accelerated Symptoms Termination) in Non Hospitalized Patients Infected With SARS-CoV-2 - Condition:   COVID-19
  Interventions:   Drug: KIN001;   Drug: KIN001-Placebo
  Sponsor:   Kinarus AG
  Recruiting

From PubMed

• Cell cycle block by p53 activation reduces SARS-CoV-2 release in infected alveolar basal epithelial A549-hACE2 cells - SARS-CoV viruses have been shown to downregulate cellular events that control antiviral defenses. They adopt several strategies to silence p53, key molecule for cell homeostasis and immune control, indicating that p53 has a central role in controlling their proliferation in the host. Specific actions are the stabilization of its inhibitor, MDM2, and the interference with its transcriptional activity. The aim of our work was to evaluate a new approach against SARS-CoV-2 by using MDM2 inhibitors…

• Molecular Modeling Targeting the ACE2 Receptor with Cannabis sativa’s Active Ingredients for Antiviral Drug Discovery against SARS-CoV-2 Infections - The emergence of a novel coronavirus that later on rendered a global pandemic, caused desperation within the communities and drove increased interest in exploring medicinal plant-based therapeutics to treat and prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections. Many medicinal plants have been reported to have antiviral, anti-inflammatory, and immunomodulatory effects that hinder, cure, or ease the symptoms of COVID-19 infection. This exploratory study seeks to…

• 5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro - Amphipathic nucleoside and non-nucleoside derivatives of pentacyclic aromatic hydrocarbon perylene are known as potent non-cytotoxic broad-spectrum antivirals. Here we report 3-methyl-5-(perylen-3-ylethynyl)-uracil-1-acetic acid and its amides, a new series of compounds based on a 5-(perylen-3-ylethynyl)-uracil scaffold. The compounds demonstrate pronounced in vitro activity against arthropod-borne viruses, namely tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV), in plaque…

• SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming - How SARS-CoV-2 penetrates the airway barrier of mucus and periciliary mucins to infect nasal epithelium remains unclear. Using primary nasal epithelial organoid cultures, we found that the virus attaches to motile cilia via the ACE2 receptor. SARS-CoV-2 traverses the mucus layer, using motile cilia as tracks to access the cell body. Depleting cilia blocks infection for SARS-CoV-2 and other respiratory viruses. SARS-CoV-2 progeny attach to airway microvilli 24 h post-infection and trigger…

• Guanylate-binding protein 1 restricts avian coronavirus infectious bronchitis virus-infected HD11 cells - The Infectious Bronchitis Virus (IBV), a coronavirus, is a key avian pathogen that causes acute and highly infectious viral respiratory diseases. IBV is an enveloped, positive-sense RNA virus, and the host factors that restrict infection and replication of the virus remain poorly understood. Guanylate-binding protein 1 (GBP1), an interferon-gamma (IFN-γ)-inducible guanosine triphosphatase (GTPase), is a major player in host immunity and provides defense against viral replication. However, the…

• CdTe QDs-sensitized TiO₂ nanocomposite for magnetic-assisted photoelectrochemical immunoassay of SARS-CoV-2 nucleocapsid protein - A sensitive, reliable, and cost-effective detection for SARS-CoV-2 was urgently needed due to the rapid spread of COVID-19. Here, a “signal-on” magnetic-assisted PEC immunosensor was constructed for the quantitative detection of SARS-CoV-2 nucleocapsid (N) protein based on Z-scheme heterojunction. Fe(3)O(4)@SiO(2)@Au was used to connect the capture antibody to act as a capture probe (Fe(3)O(4)@SiO(2)@Au/Ab(1)). It can extract target analytes selectively in complex samples and multiple electrode…

• Silver nanoparticles with excellent biocompatibility block pseudotyped SARS-CoV-2 in the presence of lung surfactant - Silver (Ag) is known to possess antimicrobial properties which is commonly attributed to soluble Ag ions. Here, we showed that Ag nanoparticles (NPs) potently inhibited SARS-CoV-2 infection using two different pseudovirus neutralization assays. We also evaluated a set of Ag nanoparticles of different sizes with varying surface properties, including polyvinylpyrrolidone (PVP)-coated and poly (ethylene glycol) (PEG)-modified Ag nanoparticles, and found that only the bare (unmodified) nanoparticles…

• Suppression of porcine hemagglutinating encephalomyelitis virus replication by resveratrol - CONCLUSION: These results indicated that resveratrol exerted antiviral effects under various drug treatment and virus infection conditions in vitro and holds promise as a treatment for PHEV infection in vivo.

• Characterization of SARS-CoV-2 omicron variants from Iran and evaluation of the effect of mutations on the spike, nucleocapsid, ORF8, and ORF9b proteins function - The SARS-CoV-2 ‘Omicron’ strain, with 15 mutations in the receptor binding domain (RBD), was detected in South Africa and rapidly spread worldwide. SARS-CoV-2 ORF9b protein by binding to the TOM70 receptor and ORF8 protein by binding to MHC-I, IF3 receptors inhibit the host’s immune response. In this study, genomics variations were evaluated for 96 samples isolated from Iran from March to July 2022 using the Nextclade web server and informatics tools. We identified the mutations occurring in the…

• Molecular insights into the in silico discovery of corilagin from Terminalia chebula as a potential dual inhibitor of SARS-CoV-2 structural proteins - The spike (S) glycoprotein and nucleocapsid (N) proteins are the crucial pathogenic proteins of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus during its interaction with the host. Even FDA-approved drugs like dexamethasone and grazoprevir are not able to curb the viral progression inside the host and are reported with adverse effects on body metabolism. In this context, we aim to report corilagin a novel, potential dual inhibitor of S and N proteins from Terminalia…

• Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline - The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology…

• Performance and correlation of ten commercial immunoassays for the detection of SARS-CoV-2 antibodies - Accurate immunoassays with a good correlation to neutralizing antibodies are required to support SARS-CoV-2 diagnosis, management, vaccine deployment, and epidemiological investigation. We conducted a study to evaluate the performance and correlation of the surrogate virus neutralization test (sVNT) and other commercial immunoassays. We tested 107 sera of COVID-19 confirmed cases from three different time points, 58 confirmed non-COVID-19 sera, and 52 sera collected before the pandemic with two…

• SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to down-regulate MHC-I surface expression - Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small-protein β(2)-microglobulin (β(2)m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells, these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those…

• Carotenoids as potential inhibitors of TNFα in COVID-19 treatment - Tumor necrosis factor-alpha (TNF-α) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. In COVID-19 patients, increased TNF-α concentration may provoke inflammatory cascade and induce the initiation of cytokine storm that may result in fatal pneumonia and acute respiratory distress syndrome (ADRS). Hence, TNFα is assumed to be a promising drug target against cytokine storm in COVID-19 patients. In the present study, we focused on finding novel…

• Infectivity of pseudotyped SARS-CoV-2 variants of concern in different human cell types and inhibitory effects of recombinant spike protein and entry-related cellular factors - Since the report of the first COVID-19 case in 2019, SARS-CoV-2 variants of concern (VOCs) have continued to emerge, manifesting diverse infectivity, evasion of host immunity and pathology. While ACE2 is the predominant receptor of SARS-CoV-2, TMPRSS2, Kim-1, NRP-1, CD147, furin, CD209L and CD26 have also been implicated as viral entry-related cofactors. To understand the variations in infectivity and pathogenesis of VOCs, we conducted infection analysis in human cells from different organ…

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