The ecology of viruses in urban rodents with a focus on SARS-CoV-2.

Wild animals are naturally infected with a range of viruses, some of which may be zoonotic. During the human COVID pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this, we sampled rats (Rattus norvegicus) and mice (Apodemus sylvaticus) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralization ability that are consistent with rats being exposed to SARS-CoV-2 and/or exposed to other viruses that result in cross-reactive antibodies.

COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient

A 25-year-old patient with a primary immunodeficiency lacking immunoglobulin production experienced a relapse after a 239-day period of persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral genetic sequencing demonstrated that SARS-CoV-2 had evolved during the infection period, with at least five mutations associated with host cellular immune recognition. Among them, the T32I mutation in ORF3a was found to evade recognition by CD4+ T cells. The virus found after relapse showed an increased proliferative capacity in vitro. SARS-CoV-2 may have evolved to evade recognition by CD4+ T cells and increased in its proliferative capacity during the persistent infection, likely leading to relapse. These mutations may further affect viral clearance in hosts with similar types of human leukocyte antigens. The early elimination of SARS-CoV-2 in immunocompromised patients is therefore important not only to improve the condition of patients but also to prevent the emergence of mutants that threaten public health. Graphical

A universal fluorescence polarization high throughput screening assay to target the SAM-binding sites of SARS-CoV-2 and other viral methyltransferases.

SARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since 2020. Currently, only limited options are available to treat SARS-CoV-2 infections for vulnerable populations. In this study, we report a universal fluorescence polarization (FP)-based high throughput screening (HTS) assay for SAM-dependent viral methyltransferases (MTases), using a fluorescent SAM-analogue, FL-NAH. We performed the assay against a reference MTase, NSP14, an essential enzyme for SARS-CoV-2 to methylate the N7 position of viral 5'-RNA guanine cap. The assay is universal and suitable for any SAM-dependent viral MTases such as the SARS-CoV-2 NSP16/NSP10 MTase complex and the NS5 MTase of Zika virus (ZIKV). Pilot screening demonstrated that the HTS assay was very robust and identified two candidate inhibitors, NSC 111552 and 288387. The two compounds inhibited the FL-NAH binding to the NSP14 MTase with low micromolar IC50. We used three functional MTase assays to unambiguously verified the inhibitory potency of these molecules for the NSP14 N7-MTase function. Binding studies indicated that these molecules are bound directly to the NSP14 MTase with similar low micromolar affinity. Moreover, we further demonstrated that these molecules significantly inhibited the SARS-CoV-2 replication in cell-based assays at concentrations not causing cytotoxicity. Furthermore, NSC111552 significantly synergized with known SARS-CoV-2 drugs including nirmatrelvir and remdesivir. Finally, docking suggested that these molecules bind specifically to the SAM-binding site on the NSP14 MTase. Overall, these molecules represent novel and promising candidates to further develop broad-spectrum inhibitors for the management of viral infections.

Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity.

Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell-cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.

Randomized controlled trials assessing efficacy of brief web-based stress management interventions for college students during the COVID pandemic.

The purpose of this study was to evaluate the efficacy of brief, self-guided web-based interventions for decreasing distress among U.S. college students during the pandemic. Three randomized controlled trials were conducted during the spring (Study 1), summer (Study 2), and fall (Study 3) 2020 terms, and were combined into one sample to increase power (N = 775). We evaluated a web-based intervention that focused on increasing present control that had been shown to be effective in several studies prior to the pandemic (e.g., Nguyen-Feng et al., 2017). This intervention was compared to an active comparison condition (psychoeducation about and reminders to engage in Centers for Disease Control and Prevention (CDC)-recommended stress management techniques) in Study 1, to a waitlist comparison in Study 2, and to both comparison conditions in Study 3. Participants were undergraduate psychology students at two campuses of a midwestern state university system. Outcomes-perceived stress (primary); depression, anxiety, and stress symptoms (secondary); and boredom (tertiary)-were assessed at pretest and posttest (and 3-week follow-up in Study 3). Differences across conditions were significant for perceived stress, stress symptoms, and boredom (but not depression or anxiety). Contrary to hypotheses, the Present Control and CDC stress management interventions were equally effective. Both were more effective than no intervention (between-group ds = -0.27 and -0.42). Both interventions were more effective for students with higher baseline stress levels. Completion and adherence rates were high for both conditions. Results suggest that very brief, self-guided stress management interventions can be effective in reducing stress among college students. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of IL-6 in coronavirus, especially in COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects both people and animals and may cause significant respiratory problems, including lung illness: Corona Virus Disease 2019 (COVID-19). Swabs taken from the throat and nose of people who have the illness or are suspected of having it have shown this pathogenic virus. When SARS-CoV-2 infects the upper and lower respiratory tracts, it may induce moderate to severe respiratory symptoms, as well as the release of pro-inflammatory cytokines including interleukin 6 (IL-6). COVID-19-induced reduction of IL-6 in an inflammatory state may have a hitherto undiscovered therapeutic impact. Many inflammatory disorders, including viral infections, has been found to be regulated by IL-6. In individuals with COVID-19, one of the primary inflammatory agents that causes inflammatory storm is IL-6. It promotes the inflammatory response of virus infection, including the virus infection caused by SARS-CoV-2, and provides a new diagnostic and therapeutic strategy. In this review article, we highlighted the functions of IL-6 in the coronavirus, especially in COVID-19, showing that IL-6 activation plays an important function in the progression of coronavirus and is a rational therapeutic goal for inflammation aimed at coronavirus.

The role of IL-6 in coronavirus, especially in COVID-19

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects both people and animals and may cause significant respiratory problems, including lung illness: Corona Virus Disease 2019 (COVID-19). Swabs taken from the throat and nose of people who have the illness or are suspected of having it have shown this pathogenic virus. When SARS-CoV-2 infects the upper and lower respiratory tracts, it may induce moderate to severe respiratory symptoms, as well as the release of pro-inflammatory cytokines including interleukin 6 (IL-6). COVID-19-induced reduction of IL-6 in an inflammatory state may have a hitherto undiscovered therapeutic impact. Many inflammatory disorders, including viral infections, has been found to be regulated by IL-6. In individuals with COVID-19, one of the primary inflammatory agents that causes inflammatory storm is IL-6. It promotes the inflammatory response of virus infection, including the virus infection caused by SARS-CoV-2, and provides a new diagnostic and therapeutic strategy. In this review article, we highlighted the functions of IL-6 in the coronavirus, especially in COVID-19, showing that IL-6 activation plays an important function in the progression of coronavirus and is a rational therapeutic goal for inflammation aimed at coronavirus.

Consecutive BNT162b2 mRNA vaccination induces short-term epigenetic memory in innate immune cells.

Consecutive mRNA vaccinations against SARS-CoV-2 reinforced both innate and adaptive immune responses. However, it remains unclear whether the enhanced innate immune responses are mediated by epigenetic regulation and, if so, whether these effects persist. Using mass cytometry, RNA-seq, and ATAC-seq, we show that BNT162b2 mRNA vaccination upregulated antiviral and IFN-stimulated gene expression in monocytes with greater effects after the second vaccination than those after the first vaccination. Transcription factor-binding motif analysis also revealed enriched IFN regulatory factors and PU.1 motifs in accessible chromatin regions. Importantly, although consecutive BNT162b2 mRNA vaccinations boosted innate immune responses and caused epigenetic changes in isolated monocytes, we showed that these effects occur only transiently and disappear 4 weeks after the second vaccination. Furthermore, single-cell RNA sequencing analysis revealed that a similar gene signature was impaired in the monocytes of unvaccinated COVID-19 patients with acute respiratory distress syndrome. These results reinforce the importance of the innate immune response in the determination of COVID-19 severity but indicate that, unlike adaptive immunity, innate immunity is not unexpectedly sustained even after consecutive vaccination. This study, which focuses on innate immmune memory, may provide novel insights into the vaccine development against infectious diseases.

International migrants and coronavirus disease 2019 vaccinations: Social Media, motivated information management, and vaccination willingness.

Objective: This study examines how those who were born outside the United States and migrated to the country in the past decade used social media and other online sites to deal with uncertainties around the coronavirus disease 2019 pandemic. In particular, we examine how they used digital communication technologies to tap into online resources and social connections both in the United States and their origin country and how various aspects of online information management were associated with their willingness to get vaccinated against the virus. Method: We conducted an online survey and in-depth interviews with international migrants aged 18-64 years who moved to the United States in 2011 or later and were living in two neighboring states in the US Midwest as of spring 2021. Since this research involves understanding how these international migrants dealt with uncertainties related to coronavirus disease 2019 vaccinations, we collected the survey and interview data when each state had a vaccination rate of less than 10% and very limited vaccination eligibility for those aged 64 years and below. Results: Our results show that international migrants" perceived uncertainty, positive and negative emotions, efficacy, and outcome expectancy affect their information seeking related to the coronavirus disease 2019 vaccination. In addition, issue salience moderates the effect between information seeking and vaccine willingness. Conclusion: This research provides relevant and timely scholarly and policy implications that help advance research in this area and better support international migrant communities during public health crises such as the coronavirus disease 2019 pandemic.

A protein-protein interaction map reveals that the Coxiella burnetii effector CirB inhibits host proteasome activity.

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91-120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection.

COVID-19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

Race/ethnicity, online information and COVID-19 vaccination: Study of minority immigrants’ internet use for health-related information

The COVID-19 pandemic aggravated existing challenges for racial/ethnic minority immigrants in the U.S. in obtaining health information and seeking health care. Based on in-depth interviews with 49 racial/ethnic minority immigrants in the U.S. Midwest, this study examines how they navigated online health information related to general health issues and in particular COVID-19, how they encounter online misinformation related to COVID-19 vaccination and their willingness to get vaccinated. Results show that participants use online health information from both the U.S. and their home country to stay informed about the pandemic, but often encounter misinformation and hate speech online. Further, participants are hesitant to correct misinformation due to contentious online environment. Additionally, findings revealed that younger participants tended to be less willing to get vaccinated due to low perceived benefits. The study suggests scholarly and practical implications for those who work in the area of health communication, digital media messaging and minority communication.

An antibody-based proximity labeling protocol to identify biotinylated interactors of SARS-CoV-2.

Elucidating the molecular interactions between virus and host is fundamental to understanding the mechanism of viral pathogenesis. Here, we present a protocol to screen SARS-CoV-2 protein interactors using an antibody-based TurboID proximity labeling approach. This technique directly identifies biotinylated peptides labeled by the TurboID-tagged viral proteins. We describe the steps to prepare biotinylated peptide samples for mass spectrometry analysis and a stringent workflow to identify biotinylated high-confidence interactors of the virus by filtering out non-specific co-purified proteins. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).

Mental health of US undergraduate and graduate students before and during the COVID-19 pandemic: Differences across sociodemographic groups.

The purposes of this study were to assess differences between sociodemographic groups in student mental health before and during the COVID-19 pandemic, to investigate whether the pandemic disproportionately affected certain groups, and to examine between-group differences in pandemic-related stressors. Data from Minnesota undergraduate and graduate students who completed an online survey in 2020 (N = 2,067) were compared to data collected from students in 2018 (N = 3,627). The survey assessed days of poor mental health, stress, stress management ability, days of adequate sleep, and pandemic-related stressors (2020 only). Multivariate analyses of variance assessed differences between study years (2020 vs. 2018), sociodemographic groups (gender, sexual orientation, race, disability, international student), and their interactions with study year in predicting mental health, and the sociodemographic groups in predicting pandemic stressors, among undergraduate and graduate students. Stress management ability decreased and sleep improved from 2018 to 2020. The sociodemographic variables most associated with poorer mental health were identifying as female, a sexual minority, or having a disability. Undergraduates reported poorer mental health than graduate students. Differences between sociodemographic groups were not larger during the pandemic, except among students with disabilities. All five sociodemographic variables were related to greater pandemic stressors in some domains.

Efficient disinfection of SARS-CoV-2-like coronavirus, pseudotyped SARS-CoV-2 and other coronaviruses using cold plasma induces spike protein damage.

Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency, and the high transmission of SARS-CoV-2 variants has raised serious concerns. Efficient disinfection methods are crucial for the prevention of viral transmission. Herein, pulse power-driven cold atmospheric plasma (CAP), a novel sterilization strategy, was found to potently inactivate SARS-CoV-2-like coronavirus GX_P2V, six strains of major epidemic SARS-CoV-2 variants and even swine coronavirus PEDV and SADS-CoV within 300 s (with inhibition rate more than 99%). We identified four dominant short-lived reactive species, ONOO-, 1O2, O2- and·OH, generated in response to CAP and distinguished their roles in the inactivation of GX_P2V and SARS-CoV-2 spike protein receptor binding domain (RBD), which is responsible for recognition and binding to human angiotensin-converting enzyme 2 (hACE2). Our study provides detailed evidence of a novel surface disinfection strategy for SARS-CoV-2 and other coronaviruses.

Applications of density functional theory in COVID-19 drug modeling.

The rapidly evolving Coronavirus 2019 (COVID-19) pandemic has led to millions of deaths around the world, highlighting the pressing need to develop effective antiviral pharmaceuticals. Recent efforts with computer-aided rational drug discovery have allowed detailed examination of drug-macromolecule interactions primarily by molecular mechanics (MM) techniques. Less widely applied in COVID-19 drug modeling is density functional theory (DFT), a quantum mechanics (QM) method that enables electronic structure calculations and elucidations of reaction mechanisms. Here, we review recent advances in applying DFT in molecular modeling studies of COVID-19 pharmaceuticals. We start by providing an overview of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs and targets, followed by a brief introduction to DFT. We then provide a discussion of different approaches by which DFT has been applied. Finally, we discuss essential factors to consider when incorporating DFT in future drug modeling research.

SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS.

The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is still unclear. In this study, we found that SARS-CoV-2 Nsp5 can induce the expression of cytokines IL-1ß, IL-6, TNF-α, and IL-2 in Calu-3 and THP1 cells. Further research found that Nsp5 enhances cytokine expression through activating the NF-κB signaling pathway. Subsequently, we investigated the upstream effectors of the NF-κB signal pathway on Nsp5 overexpression and discovered that Nsp5 increases the protein level of MAVS. Moreover, Nsp5 can promote the SUMOylation of MAVS to increase its stability and lead to increasing levels of MAVS protein, finally triggering activation of NF-κB signaling. The knockdown of MAVS and the inhibitor of SUMOylation treatment can attenuate Nsp5-mediated NF-κB activation and cytokine induction. We identified a novel role of SARS-CoV-2 Nsp5 to enhance cytokine production by activating the NF-κB signaling pathway.

US college student mental health and COVID-19: Comparing pre-pandemic and pandemic timepoints.

OBJECTIVE: To assess mental health in US undergraduates during COVID-19; to identify key pandemic-related stressors, perceived control, and coping and their associations with mental health. PARTICIPANTS: Data collected from a sample of undergraduates in April 2020 (N = 312) were compared to data collected in Spring 2017 (N = 362). METHODS: Online measures of depression, anxiety, and stress symptoms and perceived control and coping (both samples); pandemic-related stressors and perceived benefits (April 2020). RESULTS: Depression and stress symptoms were higher in April 2020 than in 2017. Most students reported perceiving at least some pandemic-related benefits. Top-rated stressors involved missing seeing friends and school-related stressors. Perceived control and approach coping were lower during the pandemic but related to better mental health; avoidant coping was higher during the pandemic and related to poorer mental health. CONCLUSIONS: Findings can inform campuses regarding how to improve student mental health during COVID and beyond.

An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity.

The global epidemic caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in the infection of over 200 million people. To extend the knowledge of interactions between SARS-CoV-2 and humans, we systematically investigate the interactome of 29 viral proteins in human cells by using an antibody-based TurboID assay. In total, 1,388 high-confidence human proximal proteins with biotinylated sites are identified. Notably, we find that SARS-CoV-2 manipulates the antiviral and immune responses. We validate that the membrane protein ITGB1 associates angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 entry. Moreover, we reveal that SARS-CoV-2 proteins inhibit activation of the interferon pathway through the mitochondrial protein mitochondrial antiviral-signaling protein (MAVS) and the methyltransferase SET domain containing 2, histone lysine methyltransferase (SETD2). We propose 111 potential drugs for the clinical treatment of coronavirus disease 2019 (COVID-19) and identify three compounds that significantly inhibit the replication of SARS-CoV-2. The proximity labeling map of SARS-CoV-2 and humans provides a resource for elucidating the mechanisms of viral infection and developing drugs for COVID-19 treatment.