- Contribution of private game ranching and captive bred operations in South Africa to white rhino Ceratotherium simum species survival conservation -
The southern white rhinoceros (SWR) Ceratotherium simum simum, like all extant rhinoceros’ species, is under global threat of extinction, due to their dwindling wild population numbers in protected areas and state-owned parks as a result of poaching. The Kruger National Park (KNP), the renowned state-owned stronghold for SWR, has suffered an estimated decline of over 75.0% of its population since 2011, with the highest annual poaching rates over the past decade and a remaining population estimated at only 2,607 animals by the end of 2020, which is an average annual population decline of -10.2% from 2008 to 2020, and 2,458 animals left by the end of June 2022. On the contrary, SWR under private custodianship and management on rewilded agro-sustainable biodiversity game ranches in South Africa (estimated currently at >8,000 animals, some of which are registered Captive Breeding Operations [CBO]; assessed CBOs contained 2,882 rhinos at the time of this study (Sep 2021), have increased in population numbers and survival rates, sustaining average annual population growth performances of 9.0%. This increase has been attributed to effective security, provision of additional habitat, dispersal, and frequent genetic exchange of rhinos between breeding subpopulations by the private sector. The conservation success of the private sector has largely been overlooked and disregarded by world conservation bodies and organizations, mostly due to misguided and prejudiced media publicity and the lack of scientific analytical assessment. Private rhino custodians and their biological/conservation breeding practices, with private agro-sustainable biodiversity wildlife management and/or captive breeding, generally being perceived and branded as either “canned” or equated to “captive zoological-gardens”. Since the commencement of the International Convention on Biodiversity, global controversy exists whereby most of mankind today perceive bio-conservation of a species to be assigned in principle solely to protected areas and state-owned parks. The unique and advantageous roles of rewilded bio-conservation and sustainable-use conservation CBOs, being a key to green-economy and natural capital in a post-Covid-19 struggle, are mostly ignored. This study serves to assess and quantify the impact of private wildlife ranching in South Africa with specific focus on its potential contribution to rhino conservation specifically for that of the SWR C.s. simum.
- Host specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome -
Hosts have evolved diverse strategies to respond to microbial infections, including the detection of pathogen-encoded proteases by inflammasome-forming sensors such as NLRP1 and CARD8. Here, we find that the 3CL protease (3CLpro) encoded by diverse coronaviruses, including SARS-CoV-2, cleaves a rapidly evolving region of human CARD8 and activates a robust inflammasome response. CARD8 is required for cell death and the release of pro-inflammatory cytokines during SARS-CoV-2 infection. We further find that natural variation alters CARD8 sensing of 3CLpro, including 3CLpro-mediated antagonism rather than activation of megabat CARD8. Likewise, we find that a single nucleotide polymorphism (SNP) in humans reduces CARD8’s ability to sense coronavirus 3CLpros, and instead enables sensing of 3C proteases (3Cpro) from select picornaviruses. Our findings demonstrate that CARD8 is a broad sensor of viral protease activities and suggests that CARD8 diversity contributes to inter- and intra-species variation in inflammasome-mediated viral sensing and immunopathology.
- Triple COVID-19 vaccination induces humoral and cellular immunity to SARS-CoV-2 with cross-recognition of the Omicron variant and IgA secretion -
COVID-19 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous COVID-19 vaccinations. All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron independently from age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed a SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to appearance of new variant-specific antibodies. In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
- SARS-CoV-2 Omicron boosting induces de novo B cell response in humans -
The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs). It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants. Here, we show that boosting with the original SARS-CoV-2 spike vaccine (mRNA-1273) or a B.1.351/B.1.617.2 (Beta/Delta) bivalent vaccine (mRNA-1273.213) induces robust spike-specific GC B cell responses in humans. The GC response persisted for at least eight weeks, leading to significantly more mutated antigen-specific MBC and bone marrow plasma cell compartments. Interrogation of MBC-derived spike-binding monoclonal antibodies (mAbs) isolated from individuals boosted with either mRNA-1273, mRNA-1273.213, or a monovalent Omicron BA.1-based vaccine (mRNA-1273.529) revealed a striking imprinting effect by the primary vaccination series, with all mAbs (n=769) recognizing the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted approach, we isolated mAbs that recognized the spike protein of the SARS-CoV-2 Omicron (BA.1) but not the original SARS-CoV-2 spike from the mRNA-1273.529 boosted individuals. The latter mAbs were less mutated and recognized novel epitopes within the spike protein, suggesting a naive B cell origin. Thus, SARS-CoV-2 boosting in humans induce robust GC B cell responses, and immunization with an antigenically distant spike can overcome the antigenic imprinting by the primary vaccination series.
- Evolution of new variants of SARS-COV-2 during the pandemic: mutation limited or selection limited? -
The recent pandemic caused by SARS-Cov-2 has witnessed an evolving succession of variants of the virus. While the phenomenon of invasion by immunity evading variants is known for other viruses such as influenza, the dynamics of the ecological and evolutionary process in the succession is little known. Since during the Covid-19 pandemic, large scale epidemiological data were collected and made available in the public domain, it is possible to seek answers to a number of evolutionary questions, which will also have public health implications. We list multiple alternative hypotheses about the origin and invasion of the variants and evaluate them in the light of epidemiological data. Our analysis shows that invasion by novel variants is selection limited and not mutation limited. Further novel variants are not the necessary and sufficient causes of the repeated waves during the pandemic. Rather there is substantial overlap between the conditions leading to a wave and those favoring selection of a partial immune evading variant. This is likely to lead to an association between invasion by new variant and the rise of a new wave. But the association is not sufficiently strong and does not support a causal role of the new variant. The dynamics of interaction between epidemiological processes and selection on viral variants have many public health implications that can guide future policies for effective control of infectious epidemics.
- A three-wave network analysis of COVID-19’s impact on schizotypal traits, paranoia and mental health through loneliness -
This manuscript is now published in open access UCL Open Environment: https://ucl.scienceopen.com/hosted-document?doi=10.14324/111.444/000092.v2 This manuscript has been submitted for publication and is likely to be edited as part of the peer-review process. Correspondence regarding this paper should be addressed to Keri Ka-Yee Wong, keri.wong@ucl.ac.uk. Background. The 2019 coronavirus (COVID-19) pandemic has impacted people’s mental wellbeing. Studies to date have examined the prevalence of mental health symptoms (anxiety, depression, loneliness), yet fewer longitudinal studies have compared across background factors and other psychological variables to identify vulnerable sub-groups. This study tests to what extent higher levels of psychotic-like experiences – indexed by schizotypal traits and paranoia – are associated with various mental health variables 6- and 12-months since April 2020. Methods. Over 2,300 adult volunteers (18-89 years, female=74.9%) with access to the study link online were recruited from the UK, USA, Greece, and Italy. Self-reported levels of schizotypy, paranoia, anxiety, depression, aggression, loneliness, and stress from three timepoints (17 April to 13 July 2020, N1 =1,599; 17 October to 31 January 2021, N2 =774; and 17 April to 31 July 2021, N3 =586) were mapped using network analysis and compared across time and background variables (sex, age, income, country). Results. Schizotypal traits and paranoia were positively associated with poorer mental health through loneliness, with no effect of age, sex, income levels, countries, and timepoints. Loneliness was the most influential variable across all networks, despite overall reductions in levels of loneliness, schizotypy, paranoia, and aggression during the easing of lockdown. Individuals with higher levels of schizotypal traits/paranoia reported poorer mental health outcomes than individuals in the low-trait groups. Conclusion. Schizotypal traits and paranoia are associated with poor mental health outcomes through self-perceived loneliness, suggesting that increasing social/community cohesion may improve individuals’ mental wellbeing in the long run.
- localcovid19now: processing and mapping COVID-19 case data at subnational scales -
The localcovid19now R package provides functionality to load, unify and visualize recent COVID-19 case data at subnational scales in order to provide localized situational reports and improve understanding of the scale of local COVID-19 transmission. The package loads data from a variety of data sources and returns the most recent estimate of recorded per capita active COVID-19 infections, the date of the most recent report, and the geometry of each region. These data can then be visualized via mapping documented per capita active infections. We also provide functionality to visualize the risk of exposure to COVID-19 given a particular event size.
- Reflections, Resilience, and Recovery: A qualitative study of the COVID-19 impact on an international general population’s mental health and priorities for support -
This paper is now published in open access UCL Open Environment: https://ucl.scienceopen.com/hosted-document?doi=10.14324/111.444/000119.v2* The impact of the coronavirus 2019 (COVID-19) pandemic on different countries and populations is well documented in quantitative studies, with some studies showing stable mental health symptoms and others showing fluctuating symptoms. However, the reasons behind why some symptoms are stable and others change are under-explored, which in turn makes identifying the types of support needed by participants themselves challenging. To address these gaps, this study thematically analysed 925 qualitative responses from five open-ended responses collected in the UCL-Penn Global COVID Study between 17 April to 31 July 2021 (wave 3). Three key themes comprised of 13 codes were reported by participants across countries and ages regarding the impact of COVID-19 on their health, both mental and physical, and livelihoods. These include: 1) Outlook on self/life, 2) Self-improvement, and 3) Loved ones (friends and family). In terms of support, while 2.91% did not require additional support, 91% wanted support beyond financial. Other unexpected new themes were also discussed regarding vulnerable populations suffering disproportionately. The pandemic has brought into sharp focus various changes in people’s mental health, physical health, and relationships. Greater policy considerations should be given to supporting citizens’ continued access to mental health when considering pandemic recovery. Keywords: COVID-19; mental health; behavioural change; qualitative; financial burden; support.
- Child Externalizing and Internalizing Behavior and Parental Well-Being During the COVID-19 Pandemic -
Author Notes This manuscript is now published in open access UCL Open Environment: https://ucl.scienceopen.com/hosted-document?doi=10.14324/111.444/ucloe.000040. This manuscript has been submitted for publication and is likely to be edited as part of the peer-review process. Correspondence regarding this paper should be addressed to Keri Ka-Yee Wong, keri.wong@ucl.ac.uk. Abstract In this study we surveyed families’ experiences with parental depression, stress, relationship conflict, and child behavioral issues during six months of the COVID-19 pandemic through the COVID-19: Global Social Trust and Mental Health Study. The current analyses used data collected from online surveys completed by adults in 66 countries from April 17, 2020-July 14, 2020 (Wave I), followed by surveys six months later at Wave II (October 17, 2020-January 31, 2021). Analyses were limited to 175 adult parents who reported living with at least one child under 18 years old at Wave I. Parents reported on children’s level of externalizing and internalizing behavior at Wave I. At Wave II, parents completed self-reported measures of stress, depression, and inter-partner conflict. Child externalizing behavior at Wave I significantly predicted higher levels of parental stress and marginally predicted parental depression at Wave II, controlling for covariates. Child internalizing behavior at Wave I did not predict parental stress or depression, controlling for covariates. Neither child externalizing nor internalizing behavior predicted parental relationship conflict. The overall findings demonstrate that child behavior likely influenced parental stress and depression during the COVID-19 pandemic. Findings suggest that mental health interventions for children and parents may improve the family system during times of disaster.
- In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury. -
The hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ failure including testicular injury and germ cell depletion. The ACE2 receptor is also expressed in the resident testicular cells however, SARS-CoV-2 infection and mechanisms of testicular injury are not fully understood. The testicular injury can likely result either from direct virus infection of resident cells or by exposure to systemic inflammatory mediators or virus antigens. We here characterized SARS-CoV-2 infection in different human testicular 2D and 3D models including primary Sertoli cells, Leydig cells, mixed seminiferous tubule cells (STC), and 3D human testicular organoids (HTO). Data shows that SARS-CoV-2 does not establish a productive infection in any testicular cell types. However, exposure of STC and HTO to inflammatory supernatant from infected airway epithelial cells and COVID-19 plasma depicted a significant decrease in cell viability and death of undifferentiated spermatogonia. Further, exposure to only SARS-CoV-2 envelope protein, but not Spike or nucleocapsid proteins led to cytopathic effects on testicular cells that was dependent on the TLR2 receptor. A similar trend was observed in the K18h-ACE2 mouse model which revealed gross pathology in the absence of virus replication in the testis. Collectively, data strongly indicates that the testicular injury is not due to direct infection of SARS-CoV-2 but more likely an indirect effect of exposure to systemic inflammation or SARS-CoV-2 antigens. Data also provide novel insights into the mechanism of testicular injury and could explain the clinical manifestation of testicular symptoms associated with severe COVID-19.
- Preclinical Study on SARS-CoV-2 Sublingual Vaccine with RBD Antigen and Poly(I:C) Adjuvant in Cynomolgus Macaques -
Mucosal vaccine for sublingual route was prepared with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and poly(I:C) adjuvant components. The efficacy of this sublingual vaccine was examined using Cynomolgus macaques. Nine of the macaque monkeys were divided into three groups of three animals; control (just 400 g poly(I:C) per head); low dose (30 g RBD and 400 g poly(I:C) per head); and high dose (150 g RBD and 400 g poly(I:C) per head), respectively. N-acetylcysteine (NAC), a mild reducing agent losing mucin barrier, was used to enhance vaccine delivery to mucosal immune cells. RBD-specific IgA antibody secreted in pituita was detected in two of three monkeys of the high dose group and one of three animals of the low dose group. RBD-specific IgG and/or IgA antibodies in plasma were also detected in these monkeys. These indicated that the sublingual vaccine stimulated mucosal immune response to produce antigen-specific secretory IgA antibodies in pituita and/or saliva. This sublingual vaccine also affected systemic immune response to produce IgG (IgA) in plasma. Little RBD-specific IgE was detected in plasma, suggesting no allergic antigenicity of this sublingual vaccine. Thus, SARS-CoV-2 sublingual vaccine consisting of poly(I:C) adjuvant showed reasonable efficacy in a non-human primate model.
- Evolution of antibody immunity following Omicron BA.1 breakthrough infection -
Understanding the evolution of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform the development of next-generation vaccines. Here, we tracked SARS-CoV-2 receptor binding domain (RBD)-specific antibody responses up to six months following Omicron BA.1 breakthrough infection in mRNA-vaccinated individuals. Cross-reactive serum neutralizing antibody and memory B cell (MBC) responses declined by two- to four-fold through the study period. Breakthrough infection elicited minimal de novo Omicron-specific B cell responses but drove affinity maturation of pre-existing cross-reactive MBCs toward BA.1. Public clones dominated the neutralizing antibody response at both early and late time points, and their escape mutation profiles predicted newly emergent Omicron sublineages. The results demonstrate that heterologous SARS-CoV-2 variant exposure drives the evolution of B cell memory and suggest that convergent neutralizing antibody responses continue to shape viral evolution.
- Evolutionary trajectory of receptor binding specificity and promiscuity of the spike protein of SARS-CoV-2 -
SARS-CoV-2 infects cells by attachment to its receptor the angiotensin converting enzyme 2 (ACE2). Regardless of the wealth of structural data, little is known about the physicochemical mechanism of interactions of the viral spike (S) protein with ACE2 and how this mechanism has evolved during the pandemic. Here, we applied experimental and computational approaches to characterize the molecular interaction of S proteins from SARS-CoV-2 variants of concern (VOC). Data on kinetics, activation- and equilibrium thermodynamics of binding of the receptor binding domain (RBD) from VOC with ACE2 as well as data from computational protein electrostatics revealed a profound remodeling of the physicochemical characteristics of the interaction during the evolution. Thus, as compared to RBDs from Wuhan strain and other VOC, Omicron RBD presented as a unique protein in terms of conformational dynamics and types of non-covalent forces driving the complex formation with ACE2. Viral evolution resulted in a restriction of the RBD structural dynamics, and a shift to a major role of electrostatic forces for ACE2 binding. Further, we investigated how the reshaping of the physicochemical qualities affect the functional properties of S proteins. Data from various binding assays revealed that SARS-CoV-2 Wuhan and Omicron RBDs manifest capacity for off-target (promiscuous) recognition of multiple unrelated proteins, but they harbor distinct reactivity patterns. This study provides mechanistic explanations for changes in the viral tropism, infectivity, and capacity to evade immune responses during evolution.
- Simplified Within Host and Dose-response Models of SARS-CoV-2 -
Understanding the mechanistic dynamics of transmission is key to designing more targeted and effective interventions to limit the spread of infectious diseases. A well-described within-host model allows explicit simulation of how infectiousness changes over time at an individual level. This can then be coupled with dose-response models to investigate the impact of timing on transmission. We collected and compared a range of within-host models used in previous studies and identified a minimally-complex model that provides suitable within-host dynamics while keeping a reduced number of parameters to allow inference and limit unidentifiability issues. Furthermore, non-dimensionalised models were developed to further overcome the uncertainty in estimates of the size of the susceptible cell population, a common problem in many of these approaches. We will discuss these models, and their fit to data from the human challenge study for SARS-CoV-2 and the model selection results, which has been performed using ABC-SMC. The parameter posteriors have then used to simulate viral-load based infectiousness profiles via a range of dose-response models, which illustrate the large variability of the periods of infection window observed for COVID-19.
- FDA-approved drug screening identified micafungin as an antiviral agent against bat-borne emerging zoonotic Pteropine orthoreovirus -
Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, severe acute respiratory syndrome (SARS) coronavirus, and SARS-CoV-2. Pteropine orthoreovirus (PRV), which spillover event occurred from fruit bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is a critical tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic effects on cultured Vero cells. Real-time quantitative PCR analysis revealed that six of eight hit compounds significantly inhibited PRV replication. Among them, micafungin used clinically as an antifungal drug, displayed a prominent antiviral effect on PRV.
Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19 - Condition: COVID-19
Interventions: Other: Olfactory training with essential oils; Other: Olfactory training with fragrance-free oils
Sponsor: Ditte Gertz Mogensen
Recruiting
COVID-19 Fourth Dose Study in Australia - Condition: COVID-19
Interventions: Biological: Tozinameran; Biological: Elasomeran; Biological: Bivalent Pfizer-BioNTech; Biological: Bivalent Moderna
Sponsors: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity
Not yet recruiting
Trial of 2nd Booster Dose of COVID-19 Vaccine - Condition: COVID-19
Intervention: Other: Invitation to get a 2nd booster dose of COVID-19 vaccine
Sponsor: Norwegian Institute of Public Health
Not yet recruiting
SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study - Condition: COVID-19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)
Not yet recruiting
SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study - Condition: COVID-19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Conversational Agent (CA); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)
Not yet recruiting
PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 - Condition: COVID-19
Interventions: Drug: PBI-0451; Drug: Placebo
Sponsor: Pardes Biosciences, Inc.
Recruiting
Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Biological: AD17002 + Formulation buffer; Biological: Placebo
Sponsors: Advagene Biopharma Co. Ltd.; Gadjah Mada University
Not yet recruiting
Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents - Condition: COVID-19
Interventions: Behavioral: Community-based Health Education based on core intervention package; Behavioral: Health Information Sharing Group
Sponsors: The Hong Kong Polytechnic University; Food and Health Bureau, Hong Kong
Recruiting
Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg; Biological: BNT162b4 5 µg; Biological: BNT162b4 10 µg; Biological: BNT162b4 15 µg
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia - Conditions: Olfactory Disorder; COVID-19
Intervention: Drug: Simvastatin
Sponsors: Washington University School of Medicine; Duke University
Not yet recruiting
Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations - Condition: COVID-19
Intervention: Behavioral: Active Intervention Group
Sponsor: Pennington Biomedical Research Center
Not yet recruiting
Cardiopulmonary Rehabilitation in Post-acute COVID-19 Syndrome - Condition: Post Acute COVID-19 Syndrome
Interventions: Other: Cardiopulmonary rehabilitation; Other: Health education
Sponsor: Taipei Medical University Shuang Ho Hospital
Not yet recruiting
Motivation, Syringe Exchange, and COVID-19 - Condition: COVID-19 Pandemic
Intervention: Behavioral: Connect2Test
Sponsors: University of Oregon; National Institute on Drug Abuse (NIDA)
Recruiting
Spikogen Booster Study - Condition: COVID-19
Intervention: Biological: SpikoGen vaccine
Sponsors: Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute Ltd; Cinnagen
Not yet recruiting
Rehabilitation Therapy for Post COVID 19 Chronic Fatigue Syndrome - Condition: Post-COVID-19 Syndrome
Intervention: Other: intensive combined rehabilitation therapy
Sponsor: Cairo University
Not yet recruiting
Pediatric Residency Training amid the COVID-19 Pandemic: Exploring the Impact of Supervision and Clinical Practice Guidelines on Clinical and Financial Outcomes - CONCLUSION: Direct supervision inhibited the negative impact of the COVID-19 pandemic on both clinical and financial outcomes of non-COVID-19 inpatient care by pediatric residents, while CPG only inhibited the negative impact on financial outcomes. Implication of This Study. In a disaster, the availability of CPG and direct supervision makes AMC hospitals able to inhibit the negative impact of disasters on clinical and financial outcomes.
Jian-Ti-Kang-Yi decoction alleviates poly(I:C)-induced pneumonia by inhibiting inflammatory response, reducing oxidative stress, and modulating host metabolism - Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory…
Structural Basis for the Inhibition of Coronaviral Main Proteases by a Benzothiazole-Based Inhibitor - The ongoing spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused hundreds of millions of cases and millions of victims worldwide with serious consequences to global health and economies. Although many vaccines protecting against SARS-CoV-2 are currently available, constantly emerging new variants necessitate the development of alternative strategies for prevention and treatment of COVID-19. Inhibitors that target the main protease (M^(pro)) of SARS-CoV-2, an…
Chemically Modified Bovine β-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks - Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine β-lactoglobulin (3HP-β-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human…
The Bovine Seminal Plasma Protein PDC-109 Possesses Pan-Antiviral Activity - Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines, and growth factors, with various functions during insemination and fertilization. The seminal plasma protein PDC-109 is one of the major soluble components of the bovine ejaculate and is crucially important for sperm motility, capacitation, and acrosome reaction. A hitherto underappreciated function of seminal plasma is its anti-microbial and…
SARS-CoV-2 RBD-Specific Antibodies Induced Early in the Pandemic by Natural Infection and Vaccination Display Cross-Variant Binding and Inhibition - The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern…
Broad-Spectrum Small-Molecule Inhibitors of the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction from a Chemical Space of Privileged Protein Binders - Therapeutically useful small-molecule inhibitors (SMIs) of protein-protein interactions (PPIs) initiating the cell attachment and entry of viruses could provide novel alternative antivirals that act via mechanisms similar to that of neutralizing antibodies but retain the advantages of small-molecule drugs such as oral bioavailability and low likelihood of immunogenicity. From screening our library, which is focused around the chemical space of organic dyes to provide good protein binders, we…
Bacteriophage-Derived Double-Stranded RNA Exerts Anti-SARS-CoV-2 Activity In Vitro and in Golden Syrian Hamsters In Vivo - Bacteriophage-derived dsRNA, known as Larifan, is a nationally well-known broad-spectrum antiviral medication. This study aimed to ascertain the antiviral activity of Larifan against the novel SARS-CoV-2 virus. Larifan’s effect against SARS-CoV-2 in vitro was measured in human lung adenocarcinoma (Calu3) and primary human small airway epithelial cells (HSAEC), and in vivo in the SARS-CoV-2 infection model in golden Syrian hamsters. Larifan inhibited SARS-CoV-2 replication both in vitro and in…
Quercetin in the Prevention and Treatment of Coronavirus Infections: A Focus on SARS-CoV-2 - The COVID-19 outbreak seems to be the most dangerous challenge of the third millennium due to its highly contagious nature. Amongst natural molecules for COVID-19 treatment, the flavonoid molecule quercetin (QR) is currently considered one of the most promising. QR is an active agent against SARS and MERS due to its antimicrobial, antiviral, anti-inflammatory, antioxidant, and some other beneficial effects. QR may hold therapeutic potential against SARS-CoV-2 due to its inhibitory effects on…
Plant Metabolites as SARS-CoV-2 Inhibitors Candidates: In Silico and In Vitro Studies - Since it acquired pandemic status, SARS-CoV-2 has been causing all kinds of damage all over the world. More than 6.3 million people have died, and many cases of sequelae are in survivors. Currently, the only products available to most of the world’s population to fight the pandemic are vaccines, which still need improvement since the number of new cases, admissions into intensive care units, and deaths are again reaching worrying rates, which makes it essential to compounds that can be used…
Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity - The replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its main protease (M^(pro)), which is a plausible therapeutic target for coronavirus disease 2019 (COVID-19). Although numerous in silico studies reported the potential inhibitory effects of natural products including cannabis and cannabinoids on SARS-CoV-2 M^(pro), their anti-M^(pro) activities are not well validated by biological experimental data. Herein, a library of minor cannabinoids…
Epigallocatechin Gallate Stabilized by Cyclodextrin Inactivates Influenza Virus and Human Coronavirus 229E - Natural products are attractive antiviral agents because they are environment-friendly and mostly harmless. Epigallocatechin gallate (EGCg), a type of catechin, is a well-known natural antiviral agent that can inhibit various viruses. However, EGCg easily oxidizes and loses its physiological activity. Although this problem can be overcome by combining EGCg with cyclodextrin (CD-EGCg), which makes it stable in water at high concentrations, the antiviral effect of this compound remains unclear….
1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants - SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and…
Molecular Bases of Serotonin Reuptake Inhibitor Antidepressant-Attributed Effects in COVID-19: A New Insight on the Role of Bradykinins - Widely available effective drugs to treat coronavirus disease-2019 (COVID-19) are still limited. Various studies suggested the potential contribution of selective serotonin-reuptake inhibitor (SSRI) antidepressants to alleviate the clinical course of COVID-19. Initially, SSRI antidepressant-attributed anti-COVID-19 activity was attributed to their direct agonistic or indirect serotonin-mediated stimulation of sigma-1 receptors (Sig1-R). Thereafter, attention was drawn to the property of SSRI…
Correlation between Type I Interferon Associated Factors and COVID-19 Severity - Antiviral type I interferons (IFN) produced in the early phase of viral infections effectively inhibit viral replication, prevent virus-mediated tissue damages and promote innate and adaptive immune responses that are all essential to the successful elimination of viruses. As professional type I IFN producing cells, plasmacytoid dendritic cells (pDC) have the ability to rapidly produce waste amounts of type I IFNs. Therefore, their low frequency, dysfunction or decreased capacity to produce type…