- Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection -
SARS-CoV-2 Omicron variants emerged in 2022 with >30 novel amino acid mutations in the spike protein alone. While most studies focus on receptor binding domain changes, mutations in the C-terminus of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. In this study, we examined three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we found that the mutant increased spike processing, consistent with prior reports for H655Y and P681H individually. Next, we generated a single N679K mutant, finding reduced viral replication in vitro and less disease in vivo. Mechanistically, the N679K mutant had reduced spike protein in purified virions compared to wild-type; spike protein decreases were further exacerbated in infected cell lysates. Importantly, exogenous spike expression also revealed that N679K reduced overall spike protein yield independent of infection. Although a loss-of-function mutation, transmission competition demonstrated that N679K had a replication advantage in the upper airway over wild-type SARS-CoV-2 in hamsters, potentially impacting transmissibility. Together, the data show that N679K reduces overall spike protein levels during Omicron infection, which has important implications for infection, immunity, and transmission.
- A large-scale serological survey in pets from October 2020 through June 2021 in France shows significantly higher exposure to SARS-CoV-2 in cats -
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect many animals, including pets such as dogs and cats. Many studies have documented infection in companion animals by bio-molecular and serological methods. However, only a few have compared seroprevalence in cats and dogs from the general population, and these studies were limited by small sample sizes and collections over short periods. Our goal was to obtain a more accurate evaluation of seroprevalence in companion animals in France and to determine whether cats and dogs differ in their exposure to SARS-CoV-2. For this purpose, we conducted an extensive SARS-CoV-2 serological survey of 2036 cats and 3577 dogs sampled by veterinarians during medical examinations in clinics throughout France. Sampling was carried out from October 2020 through June 2021, a period encompassing the second and third waves of SARS-CoV-2 infections in humans in the country. Using a microsphere immunoassay targeting receptor binding domain and trimeric spike protein, we found 7.1% seroprevalence in pets, in a subset of 308 seropositive samples, 26.3% had neutralizing antibodies. We found that cats were significantly more likely to test positive than dogs, with seropositivity rates of 9.3% and 5.9% in cats and dogs, respectively. Finally, data for both species showed that seroprevalence was lower in older animals and was not associated with the date of sampling or the sex of the animal. Our results show that cats are significantly more sensitive to SARS-CoV-2 than dogs, in line with experimental studies showing that cats are more susceptible than dogs. This study reinforces that pets are commonly infected or exposed to SARS-CoV-2, emphasizing the importance of a One-Health approach to the SARS-CoV-2 pandemic and raising the question of vaccination of companion animals in close contact with humans.
- Assessing the Impact of COVID-19 Pandemic on Vulnerable Populations in Bangladesh -
COVID-19 has affected all classes of people over the world in many ways. In major cases, the impact of COVID-19 on vulnerable group of people is overlooked though they are the major part of the society. Thus, this paper aims at investigating the impacts of COVID-19 on vulnerable people in Bangladesh intensively. Using literature review and case studies, this paper finds some interesting findings. The daily income of poor classes of people like day laborers, Rickshaw pullers, transport workers and so on reduced by 64.37 percent during COVID-19 situation. On the other hand, about 3.7 million new poor emerged amid this pandemic. Amid this pandemic, about 50 percent of women-led enterprises are laying off 76-100 percent of their workers while about 2.14 million garment workers were laid off. More effective policies should be taken to tackle the adverse impacts of COVID-19 pandemic on vulnerable populations than what is already taken by the government and NGOs.
- Different paths to COVID-19’s conspiratorial beliefs for the religious and spiritual: The roles of analytic and open-minded thinking -
With the threat of COVID-19, conspiratorial beliefs have proliferated, and people’s religiosity has risen. However, religiosity may only capture a narrow range of people’s meta-physical beliefs, spirituality may capture other aspects, and both of which may be associated with conspiratorial beliefs differently. To better understand the distinction between these traits, in a community sample of 662 Poles, we examined the correlations between them and misperceptions about COVID-19 (i.e., conspiracy and false factual beliefs) and the mediating role of analytic thinking and a tendency to be open-minded about evidence. Religiosity and spirituality were associated with misperceptions—directly and indirectly—but the associations were positive in the former and negative in the latter. The research points to the importance of studying both religiosity and spirituality in the context of cognition and misperceptions.
- Economic geography of contagion: A study on Covid-19 outbreak in India -
We propose a mechanism based on regional inequality in economic activity to explain the heterogeneity in the spread of Covid-19 and test it using data from India. The contagion is expected to spread at a higher rate in regions characterized by greater movements of goods and service. We argue that mobility will be higher in regions with greater degree of intra-regional inequality in economic activity. Such regions are usually characterized by core-periphery economic structure in which the periphery remains dependent on the core for the supply of jobs, goods, and services. Such dependence leads to greater degree of mobility between the core and periphery which in turn leads to higher rate of contagion. Using nightlights data to measure regional inequality, we find evidence in support of our hypothesis. Using mobility data, we provide direct evidence in support of our proposed channel; the positive relationship between regional inequality and Covid-19 infection is driven by mobility. Our findings suggest that policy responses to contain Covid-19 contagion needs to be heterogeneous across India where the priority areas can be chosen ex ante based on a regional inequality-based criterion.
- Antimicrobial peptides and other potential biomarkers of critical illness in Sars-CoV-2 patients with acute kidney injury -
Antimicrobial peptides (AMPs) are a complex network of 10-100 amino acid sequence molecules, widely distributed in Nature. Even though more than 300 AMPs have been described in mammals, cathelicidins and defensins remain the most investigated to date. Some publications examined the role of AMPs in COVID-19, but the findings are preliminary and in vivo studies are still lacking. Here, we report the plasma levels of five AMPs (LL-37, α-defensin 1, α-defensin 3, β-defensin 1 and β-defensin 3) and five cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, interferon-gamma and monocyte chemoattractant protein-1), in 15 healthy volunteers, 36 COVID-19 patients without Acute Kidney Injury (AKI) and 17 COVID-19 patients with AKI, since AKI is a well-known marker of worse prognosis in Sars-CoV-2 infections. We found increased levels of α-defensin 1, α-defensin 3 and β-defensin 3, but not LL-37 or β-defensin 3, in our COVID-19 population, when compared with the healthy controls, in conjunction with higher levels of interleukin-6, interleukin-10, interferon-gamma and monocyte chemoattractant protein-1, putting in evidence that these AMPs and cytokines may have an important role in the systemic inflammatory response and tissue damage that characterizes severe COVID-19.
- COVID-19 and socioeconomic context in Bangladesh: Discussion from a gendered point of view -
The COVID-19 affected communities and the economy beyond public health. The epidemic is expected to increase global poverty and inequality, making it crucial to study its effects. Several international organisations determined that a “new recession” was underway due to the global pandemic’s destructive effects on the financial, social, and personal spheres. Despite their best efforts, many undeveloped nations are fighting the pandemic’s aftereffects. Bangladesh is like other nations. Global economic and social changes will lead to new difficulties in the near future. Thus, studying COVID’s effects from a variety of perspectives, including gender, is crucial and timely. This paper explores the aftermath of the epidemic, focusing on the plight of women workers. In doing so, it sheds light on a particularly marginalised group, including maids and housekeepers, who have been denied benefits and recognition for their job.
- Psychometric Evaluation of The Fear of COVID-19 Scale Among Chinese Population -
Background. Fear is a negative emotional reaction to or persistent worry over an imminent public health event like COVID-19. The COVID-Fear Scale was developed in many countries, but not in China. The current study aims to examined the psychometric properties of Chinese version of the Fear of COVID-19 Scale. Methods. Translation into Chinese and back-translation into English were conducted firstly. Item analysis and exploratory factor analysis in Sample 1, followed by validity tests in Sample 2). Likely, test-rest reliability was conducted in Sample 3. Results. A bifactor structure of Chinese version of FCV-19S with a general fear factor and two orthogonal group factors with fear thoughts and physical response was confirmed. Besides, it has good internal consistency reliability (α=.92), composite reliability (CR=.92) and validity correlation validity. Conclusion. The results of the present study confirmed that the Chinese version of FCV-19S has good psychometric properties in the Chinese communities.
- Epidemiology of mental health problems in COVID-19: a review -
The novel coronavirus disease (COVID-19) has become a pandemic affecting health and wellbeing globally. In addition to the physical health, economic, and social implications, the psychological impacts of this pandemic are increasingly being reported in the scientific literature. This narrative review reflected on scholarly articles on the epidemiology of mental health problems in COVID-19. The current literature suggests that people affected by COVID-19 may have a high burden of mental health problems, including depression, anxiety disorders, stress, panic attack, irrational anger, impulsivity, somatization disorder, sleep disorders, emotional disturbance, posttraumatic stress symptoms, and suicidal behavior. Moreover, several factors associated with mental health problems in COVID-19 are found, which include age, gender, marital status, education, occupation, income, place of living, close contact with people with COVID-19, comorbid physical and mental health problems, exposure to COVID-19 related news and social media, coping styles, stigma, psychosocial support, health communication, confidence in health services, personal protective measures, risk of contracting COVID-19, and perceived likelihood of survival. Furthermore, the epidemiological distribution of mental health problems and associated factors were heterogeneous among the general public, COVID-19 patients, and healthcare providers. The current evidence suggests that a psychiatric epidemic is cooccurring with the COVID-19 pandemic, which necessitates the attention of the global health community. Future epidemiological studies should emphasize on psychopathological variations and temporality of mental health problems in different populations. Nonetheless, multipronged interventions should be developed and adopted to address the existing psychosocial challenges and promote mental health amid the COVID-19 pandemic.
- The blending of bending: how we engage with the world of Avatar: The Last Airbender through memes -
People often use memes to express their ideological stance on real world events. This study departs from a recent COVID-19-related meme which makes use of elements known from the animated television series Avatar: The Last Airbender (ATLA) and Avatar: Legend of Korra (LOK), and asks how it came to be and how stance is conveyed through them. After acknowledging the impact of the series, conceptual blending theory is adopted to investigate the worldbuilding of the macrocosm in ATLA. This is identified as a correlative network, which acts as the blended space of multiple input spaces consisting of intertextual references. The world of ATLA then functions as a new input space which is updated with modern elements, resulting in the blend of LOK. Minor blends are identified in the hybrid animals that occupy the fictional world. Lastly, it is shown how the selection of a particular input element for participation in meme blends already conveys an ideological stance, rather than only emerging through readers’ eyes.
- Legal hunting for conservation of highly threatened species: The case of African rhinos -
Legal hunting of highly threatened species – and especially the recreational practice of ‘trophy hunting’ – is controversial with selected ethical objections being increasingly voiced. Less attention has been paid to how hunting (even of threatened species) can be useful as a conservation tool, and likely outcomes if this was stopped. As case studies, we examine the regulated legal hunting in South Africa and Namibia of two African rhino species. Counter-intuitively, removing a small number of specific males can enhance population demography and genetic diversity, encourage range expansion, and generate meaningful socio-economic benefits to help fund effective conservation (facilitated by appropriate local institutional arrangements). Legal hunting of these species has been sustainable, as very small proportions of the populations of both species are hunted each year, and numbers of both today are higher in these countries than when controlled recreational hunting began. Terminating this management option and funding source could have negative consequences at a time when rhinos are being increasingly viewed as liabilities and COVID-19 has significantly impacted revenue generation for wildlife areas. Provided that there is appropriate governance and management, conservation of certain highly threatened species can be supported by cautiously selective and limited legal hunting.
- Human complement Factor H and Properdin act as soluble pattern recognition receptors and differentially modulate SARS-CoV-2 Infection -
Severe cases of SARS-CoV-2 infection are characterised by an imbalanced immune response, excessive inflammation, and the development of acute respiratory distress syndrome, which can lead to multiorgan failure and death. Several studies have demonstrated dysregulated complement activity as an indicator of immunopathogenesis in the SARS-CoV-2 infection. Notably, the complement alternative pathway has been implicated in driving the excessive inflammation during severe SARS-CoV-2 infection. Reduced levels of factor H (FH), a down-regulator of the alternative pathway, and increased levels of properdin (Factor P/FP), the only known up-regulator of the alternative pathway, have been observed in individuals with severe COVID-19 infection. The present study investigated the complement activation-independent, and a more direct role of FH and FP against SARS-CoV-2 infection. Using direct ELISA, the interactions of FH and FP with the SARS-CoV-2 spike (S) and receptor binding domain (RBD) were assessed. Using S protein expressing lentiviral pseudotypes, the cell binding and luciferase-based virus entry assays were employed to assess the potential modulatory effects of FH, FP, and recombinant thrombospondin repeats 4 and 5 (TSR4+5) on SARS-CoV-2 cell entry. We also evaluated the immunomodulatory functions of FH and FP in the cytokine response triggered by SARS-CoV-2 pseudotypes via RT-qPCR. SARS-CoV-2 S and RBD proteins were found to bind both FH and FP. Treatment of A549 cells expressing human ACE2 and TMPRSS2 with FP or TSR4+5 resulted in increased cell entry and binding of SARS-CoV-2 pseudotypes. In silico studies revealed that FP increases affinity between SARS-CoV-2 and host ACE2. The impact of FP on viral cell entry and binding was reversed by anti-FP antibody treatment in A549-hACE2+TMPRSS2 cells. However, FH treatment reduced the cell entry and binding of SARS-CoV-2 lentiviral pseudotypes. Furthermore, the A549-hACE2+TMPRSS2 cells challenged with SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes pre-treated with FP or TSR4+5, exhibited upregulation of the transcripts of pro-inflammatory cytokines, such as IL-1{beta}, IL-8, IL-6, TNF-, IFN- and RANTES (as well as NF-kB). Conversely, FH pre-treatment downregulated the expression of these pro-inflammatory cytokines. Treatment of A549-hACE2+TMPRSS2 cells with FP increased S protein-mediated NF-kB activation, while FH treatment reduced it. These findings suggest that FH may act as an inhibitor of SARS-CoV-2 cell entry and binding, thereby attenuating the infection-associated inflammatory response in a complement activation-independent manner. FP may contribute to viral cell entry, binding, and exacerbating the immune response. That may result in potentially influencing the severity of the infection.
- Explaining viral pandemics with help from Theology and Physics - Alternative Hypotheses. -
Pathogens have been plaguing humans since time immemorial. One characteristic feature is repetition of pandemics by the same pathogen(s) resulting in devastation. However, starting CE 1880, the offending pathogens have been different with every episode. Borrowing concepts from theology and physics, this article tries to proffer answers to some aspects observed regarding Viruses, Vectors, and Humans, and thereby tries to redefine our thinking on the concepts of viral infections. These aspects being: how pandemics occur in the first instance, the rapid global spread of the current Covid-19 Pandemic and will the humanity be able to control such pandemics in future.
- Neuron- and microglia-specific immunoexpression in steroid-independent male sexual behaviour in castrated B6D2F1 male mice -
Sexual behaviour is necessary for procreation for several species and is traditionally viewed to be regulated by sex steroid hormones. However, several species exhibit steroid-independent sexual behaviour, and its molecular understanding is only beginning to be uncovered. The main goal of our experiment was to provide new insight into cell-specific roles that both neuronal and non-neuronal cells may play in steroid-independent male sexual behaviour. Forty B6D2F1 hybrid male mice underwent orchidectomy and were tested for reinstatement of steroid-independent male sexual behaviour after an extended period of social isolation caused by the COVID-19-mandated laboratory shutdown. After 62 weeks post-orchidectomy, 20.59% demonstrated reinstatement of steroid-independent male sexual behaviour (identified as steroid-independent persistent maters), while 23.53% of the males did not display steroid-independent male sexual behaviour (identified as steroid-independent non-maters). Using flow cytometry, we compared the preoptic area immunoexpression in NeuN+ neurons and Iba1+ microglia between steroid-independent persistent maters and steroid-independent non-maters (N = 5-6 per group). We found neuronal immunoexpression up-regulated for amyloid precursor protein and androgen receptor, as well as down-regulated for glucocorticoid receptor in steroid-independent persistent maters compared to steroid-independent non-maters. In conjunction, microglial immunoexpression of amyloid precursor protein was up-regulated in steroid-independent persistent maters compared to steroid-independent non-maters. These data suggest there are cell-specific immunoexpression differences, including the role of non-neuronal cells in steroid-independent male sexual behaviour.
- Comparative Reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data. -
Objectives: Africa has experienced fewer coronavirus disease 2019 (COVID-19) cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa. Method: We built a susceptible-exposed-infected-recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar. Finding: Senegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination in Tunisia and Senegal on model parameters was evaluated. Interpretation: Loss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. Severe acute respiratory syndrome coronavirus 2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.
Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition: COVID-19
Intervention: Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine
Sponsor: PT Bio Farma
Not yet recruiting
Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial - Condition: COVID-19
Interventions: Drug: Ivermectin Tablets; Drug: Colchicine 0.5 MG; Drug: Standared managment
Sponsor: Ain Shams University
Completed
A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01E-2; Biological: SCTV01E
Sponsor: Sinocelltech Ltd.
Not yet recruiting
COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists - Condition: COVID-19
Interventions: Behavioral: Standard implementation webinar and online training; Behavioral: Virtual facilitation
Sponsors: University of North Carolina, Chapel Hill; University of Arkansas; University of South Carolina; National Institute on Minority Health and Health Disparities (NIMHD)
Not yet recruiting
Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+ - Condition: COVID-19
Intervention: Device: Resistance Training
Sponsor: Józef Piłsudski University of Physical Education
Recruiting
LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients - Conditions: COVID-19; Hospitalized COVID-19 Patients
Interventions: Drug: Lopinavir / Ritonavir; Drug: Remdesivir (RDV); Drug: Tocilizumab; Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
Sponsors: Lebanese University; Hospital Saydet Zgharta University Medical Center
Recruiting
Multimodal Long Covid19 - Condition: Long COVID-19 Syndrome
Intervention: Other: Multimodal intervention in Long Covid19
Sponsors: Universidad de Magallanes; Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG; Clinical Hospital Dr. Lautaro Navarro Avaria
Active, not recruiting
Comprehensive Imaging Exam of Convalesced COVID-19 Patients - Conditions: COVID-19; COVID Long-Haul
Interventions: Other: Magnetic Resonance Imaging; Other: Ultra-High Resolution Computed Tomography (CT) Scan
Sponsors: Johns Hopkins University; Canon Medical Systems, USA
Enrolling by invitation
UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study) - Conditions: COVID-19 Pandemic; COVID-19 Vaccines
Interventions: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg
Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia
Recruiting
Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults - Condition: COVID-19
Interventions: Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection; Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection
Sponsor: Clover Biopharmaceuticals AUS Pty Ltd
Not yet recruiting
The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002 - Condition: COVID-19
Interventions: Biological: LYB002V14; Biological: LYB002V14A; Biological: LYB002CA
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College
Active, not recruiting
Phase 2/3 Heterologous Boosting Study With Different Dose Levels of Monovalent SARS-CoV-2 rS Vaccines - Condition: COVID-19
Interventions: Biological: NVX-CoV2373 (5μg); Biological: NVX-CoV2601 (5μg); Biological: NVX-CoV2601(5μg); Biological: NVX-CoV2601 (35μg); Biological: NVX-CoV2601(35μg); Biological: NVX-CoV2601(50μg); Biological: Bivalent BA.4/5
Sponsor: Novavax
Not yet recruiting
Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease - Conditions: COVID-19; Renal Insufficiency, Chronic
Intervention: Drug: Nirmatrelvir/ritonavir
Sponsor: Chinese PLA General Hospital
Recruiting
The Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001 - Conditions: COVID-19; Vaccine Reaction
Interventions: Biological: LYB001; Biological: CoronaVac
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College
Active, not recruiting
Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome - Condition: Post-Acute COVID-19 Syndrome
Interventions: Drug: Placebo; Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]
Sponsor: Hellenic Institute for the Study of Sepsis
Not yet recruiting
Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro - Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence. Methods: We…
Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2 - Since the outbreak of the novel coronavirus nearly 3 years ago, the world’s public health has been under constant threat. At the same time, people’s travel and social interaction have also been greatly affected. The study focused on the potential host targets of SARS-CoV-2, CD13, and PIKfyve, which may be involved in viral infection and the viral/cell membrane fusion stage of SARS-CoV-2 in humans. In this study, electronic virtual high-throughput screening for CD13 and PIKfyve was conducted…
Investigation of oxidative, inflammatory and apoptotic effects of favipiravir use alone and combined with vitamin C on brain tissue of elderly rats - Favipiravir is a nucleoside analogue antiviral drug and inhibits the replication of many RNA viruses, especially influenza viruses. Favipiravir has also been used to treat patients with mild to moderate COVID-19 disease. However, various side effects, including neurological side effects, have been reported related to the use of favipiravir. Therefore, in this study, we aimed to investigate the possible effects of favipiravir alone or in combination with vitamin C on aged rats’ brain tissue and…
In silico identification of D449-0032 compound as a putative SARS-CoV-2 Mpro inhibitor - The SARS-CoV-2 pandemic originated the urgency in developing therapeutic resources for the treatment of COVID-19. Despite the current availability of vaccines and some antivirals, the occurence of severe cases of the disease and the risk of the emergence of new virus variants still motivate research in this field. In this context, this study aimed at the computational prospection of likely inhibitors of the main protease (M^(pro)) of SARS-CoV-2 since inhibiting this enzyme leads to disruption of…
Synthesis of multivalent sialyllactose-conjugated PAMAM dendrimers: Binding to SARS-CoV-2 spike protein and influenza hemagglutinin - Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and influenza viruses have spread around the world at an unprecedented rate. Despite multiple vaccines, new variants of SARS-CoV-2 and influenza have caused a remarkable level of pathogenesis. The development of effective antiviral drugs to treat SARS-CoV-2 and influenza remains a high priority. Inhibiting viral cell surface attachment represents an early and efficient means to block virus infection. Sialyl glycoconjugates, on…
Nanobodies with cross-neutralizing activity provide prominent therapeutic efficacy in mild and severe COVID-19 rodent models - The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency, which underscores the urgent need for universal therapeutic antibody intervention for clinical patients. Here, we screened three alpacas-derived nanobodies (Nbs) with neutralizing activity from twenty RBD-specific Nbs. The three Nbs were fused with the Fc domain of human IgG, namely aVHH-11-Fc, aVHH-13-Fc and aVHH-14-Fc, which could specifically bind RBD protein…
Janus kinase inhibition in juvenile idiopathic arthritis - No abstract
Patch-clamp studies and cell viability assays suggest a distinct site for viroporin inhibitors on the E protein of SARS-CoV-2 - CONCLUSIONS: This study demonstrates direct inhibition of the SARS-CoV-2 E protein by classical viroporin inhibitors. Ivermectin and milbemycin inhibit the E protein channel but their cytotoxicity argues against clinical application.
Structural basis for the inhibition of coronaviral main proteases by ensitrelvir - Main protease (M^(pro)) is a highly conserved cysteine protease that plays a vital role in the replication of coronaviruses, making it an attractive pan-coronaviral therapeutic target. Ensitrelvir (S-217622), developed by Shionogi, is the first orally active non-covalent, non-peptidic SARS-CoV-2 M^(pro) inhibitor, which also displays antiviral efficacy against other human coronaviruses as well as SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). Here, we report the crystal…
Kaempferol inhibits SARS-CoV-2 invasion by impairing heptad repeats-mediated viral fusion - CONCLUSIONS: Kae prevents SARS-CoV-2 infection by blocking membrane fusion and possesses a broad-spectrum anti-fusion ability. These findings provide valuable insights into potential benefits of Kae-containing botanical products as a complementary prophylaxis, especially during the waves of breakthrough infections and re-infections.
Prologue: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 Annual Meeting - The 2022 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held from July 14 to 17, 2022, in New York City, New York, USA, and was attended by 420 rheumatologists, dermatologists, basic scientists, allied health professionals, patient research partners, and industry partners from 31 countries. A GRAPPA executive retreat, a Trainee Symposium, and the Patient Research Partners Network meeting were held prior to the annual meeting….
NETosis promotes chronic inflammation and fibrosis in systemic lupus erythematosus and COVID-19 - Pulmonary fibrosis, a serious complication of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19), leads to irreversible lung damage. However, the underlying mechanism of this condition remains unclear. In this study, we revealed the landscape of transcriptional changes in lung biopsies from individuals with SLE, COVID-19-induced pulmonary fibrosis, and idiopathic pulmonary fibrosis (IPF) using histopathology and RNA sequencing, respectively. Despite the diverse etiologies…
Structure basis of two nanobodies neutralizing SARS-CoV-2 Omicron variant by targeting ultra-conservative epitopes - The evolving SARS-CoV-2 Omicron strain has repeatedly caused widespread disease epidemics, and effective antibody drugs continue to be in short supply. Here, we identified a batch of nanobodies with high affinity for receptor binding domain (RBD) of SARS-CoV-2 spike protein, separated them into three classes using high performance liquid chromatography (HPLC), and then resolved the crystal structures of the ternary complexes of two non-competing nanobodies (NB1C6 and NB1B5) with RBD using X-ray…
Repurposing the Medicines for Malaria Venture’s COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice - Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world’s population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the “Medicines for Malaria Venture”…
Targeting 2-Oxoglutarate-Dependent Dioxygenases Promotes Metabolic Reprogramming That Protects against Lethal SARS-CoV-2 Infection in the K18-hACE2 Transgenic Mouse Model - Dysregulation of host metabolism is a feature of lethal SARS-CoV-2 infection. Perturbations in α-ketoglutarate levels can elicit metabolic reprogramming through 2-oxoglutarate-dependent dioxygenases (2-ODDGs), leading to stabilization of the transcription factor HIF-1α. HIF1-α activation has been reported to promote antiviral mechanisms against SARS-CoV-2 through direct regulation of ACE2 expression (a receptor required for viral entry). However, given the numerous pathways HIF-1α serves to…