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1.
Nat Microbiol ; 7(10): 1635-1649, 2022 10.
Article in English | MEDLINE | ID: covidwho-2050394

ABSTRACT

Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis of epitope location, neutralization mechanism and analysis of antibody binding to spike variants, we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of the identified population antibody response. These substitutions, including L452R (present in the Delta variant), disrupt interactions mediated by the VH1-69-specific hydrophobic HCDR2 to impair antibody-antigen association, enabling variants to escape. The first Omicron variants were sensitive to antibody R1-32 but subvariants that harbour L452R quickly emerged and spread. Our results provide insights into how SARS-CoV-2 variants emerge and evade host immune responses.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Formation , Epitopes/genetics , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
2.
JMIR Form Res ; 6(9): e38589, 2022 Sep 19.
Article in English | MEDLINE | ID: covidwho-2039598

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, increased social media usage has led to worsened mental health outcomes for many people. Moreover, due to the sociopolitical climate during the pandemic, the prevalence of online racial discrimination has contributed to worsening psychological well-being. With increases in anti-Asian hate, Asian and Asian American social media users may experience the negative effects of online racial discrimination in addition to the reduced psychological well-being resulting from exposure to online COVID-19 content. OBJECTIVE: This study aims to investigate the impact of COVID-19-related social media use and exposure to online racial discrimination during the pandemic on the mental health outcomes (ie, anxiety, depression, and secondary traumatic stress [STS]) of Asian Americans compared with those of non-Asian Americans. In addition, this study explores the mediating role of negative affect and the moderating role of racial/ethnic identification. METHODS: An online survey was conducted through Amazon Mechanical Turk and a university-wide research portal from March 3 to March 15, 2021. A total of 1147 participants took the survey. Participants' social media usage related to COVID-19 and exposure to 2 online forms of racial discrimination (individual and vicarious), mental health outcomes (anxiety, depression, and STS), racial/ethnic identification, negative affect, and demographics were assessed. RESULTS: Our results showed that COVID-19-related social media use, individual discrimination, and vicarious discrimination were predictors of negative mental health outcomes (anxiety, depression, and STS). Asian Americans reported higher vicarious discrimination than Latinx and White Americans, but Asian Americans' mental health outcomes did not differ substantially from those of the other racial/ethnic groups. Racial/ethnic identification moderated the relationship between both types of discrimination and STS, and negative affect served as a mediator between both types of discrimination and all 3 mental health outcomes. CONCLUSIONS: These results suggest that social media exposure continues to have a dire effect on mental health during the COVID-19 pandemic. This study helps to contextualize the rise of anti-Asian American hate and its impact on mental health outcomes in the United States.

3.
J Health Commun ; 27(5): 343-352, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1984802

ABSTRACT

This study aims to examine how the process of online support obtainment may affect cognitive and behavioral coping during a public crisis. A cross-sectional online survey (N = 555) was conducted during the early stage of the COVID-19 pandemic in the U.S. Our findings revealed that informational support, obtained primarily through passive and private online involvement, led to increased risk perceptions of COVID-19; emotional support, obtained mainly via private online involvement, appeared to elicit higher perceived efficacy to cope with the crisis. People's engagement in preventive behaviors was found to be affected by efficacy perceptions, but not by risk perceptions. The results suggested that online social support functioned as a double-edged sword to affect people's coping with a public crisis.


Subject(s)
COVID-19 , Pandemics , Adaptation, Psychological , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Humans , Pandemics/prevention & control , SARS-CoV-2 , Social Support
4.
Molecules ; 27(10)2022 May 23.
Article in English | MEDLINE | ID: covidwho-1953751

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CLpro) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8H-indeno[1,2-d]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CLpro. Among them, the representative compound 7a displayed inhibitory activity with an IC50 of 1.28 ± 0.17 µM against SARS-CoV-2 3CLpro. Molecular docking of 7a against 3CLpro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CLpro.


Subject(s)
COVID-19 , Protease Inhibitors , COVID-19/drug therapy , Cysteine Endopeptidases/chemistry , Humans , Molecular Docking Simulation , Pandemics , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , SARS-CoV-2 , Thiazoles/pharmacology , Viral Proteins/metabolism
5.
Inf Process Manag ; 59(4): 102990, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1867287

ABSTRACT

Documenting the emergent social representations of COVID-19 in public communication is necessary for critically reflecting on pandemic responses and providing guidance for global pandemic recovery policies and practices. This study documents the dynamics of changing social representations of the COVID-19 pandemic on one of the largest Chinese social media, Weibo, from December 2019 to April 2020. We draw on the social representation theory (SRT) and conceptualize topics and topic networks as a form of social representation. We analyzed a dataset of 40 million COVID-19 related posts from 9.7 million users (including the general public, opinion leaders, and organizations) using machine learning methods. We identified 12 topics and found an expansion in social representations of COVID-19 from a clinical and epidemiological perspective to a broader perspective that integrated personal illness experiences with economic and sociopolitical discourses. Discussions about COVID-19 science did not take a prominent position in the representations, suggesting a lack of effective science and risk communication. Further, we found the strongest association of social representations existed between the public and opinion leaders and the organizations' representations did not align much with the other two groups, suggesting a lack of organizations' influence in public representations of COVID-19 on social media in China.

6.
Molecules ; 27(10):3359, 2022.
Article in English | MDPI | ID: covidwho-1857876

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CLpro) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8H-indeno[1,2-d]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CLpro. Among them, the representative compound 7a displayed inhibitory activity with an IC50 of 1.28 ±0.17 μM against SARS-CoV-2 3CLpro. Molecular docking of 7a against 3CLpro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CLpro.

7.
Small Methods ; 6(7): e2200387, 2022 07.
Article in English | MEDLINE | ID: covidwho-1850249

ABSTRACT

The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel ß-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of ß-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.


Subject(s)
COVID-19 , Sharks , Single-Domain Antibodies , Animals , Mice , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
8.
Bioorg Med Chem Lett ; 58: 128526, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1814173

ABSTRACT

The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (Mpro) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 Mpro inhibition with an IC50 value of 116 nM and selectivity against SARS-CoV-2 Mpro when compared to PLpro and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Drug Discovery , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , Thiazoles/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , COVID-19/drug therapy , Coronavirus 3C Proteases/metabolism , Humans , Microbial Sensitivity Tests , Molecular Structure , Protease Inhibitors/chemical synthesis , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , Thiazoles/chemical synthesis , Thiazoles/chemistry
10.
J Immunol ; 206(9): 2146-2159, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1181676

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients developing severe illness or even death. Disease severity has been associated with increased levels of proinflammatory cytokines and lymphopenia. To elucidate the atlas of peripheral immune response and pathways that might lead to immunopathology during COVID-19 disease course, we performed a peripheral blood RNA sequencing analysis of the same patient's samples collected from symptom onset to full recovery. We found that PBMCs at different disease stages exhibited unique transcriptome characteristics. We observed that SARS-CoV-2 infection caused excessive release of inflammatory cytokines and lipid mediators as well as an aberrant increase of low-density neutrophils. Further analysis revealed an increased expression of RNA sensors and robust IFN-stimulated genes expression but a repressed type I IFN production. SARS-CoV-2 infection activated T and B cell responses during the early onset but resulted in transient adaptive immunosuppression during severe disease state. Activation of apoptotic pathways and functional exhaustion may contribute to the reduction of lymphocytes and dysfunction of adaptive immunity, whereas increase in IL2, IL7, and IL15 may facilitate the recovery of the number and function of lymphocytes. Our study provides comprehensive transcriptional signatures of peripheral blood response in patients with moderate COVID-19.


Subject(s)
COVID-19/blood , Cytokines/blood , Disease Progression , Inflammation Mediators/blood , Leukocytes, Mononuclear/metabolism , RNA-Seq , SARS-CoV-2/metabolism , Adult , Aged , Female , Gene Expression Regulation , Humans , Leukocytes, Mononuclear/virology , Longitudinal Studies , Male , Middle Aged
11.
Biosens Bioelectron ; 166: 112471, 2020 Oct 15.
Article in English | MEDLINE | ID: covidwho-670678

ABSTRACT

The infection and spread of pathogens (e.g., COVID-19) pose an enormous threat to the safety of human beings and animals all over the world. The rapid and accurate monitoring and determination of pathogens are of great significance to clinical diagnosis, food safety and environmental evaluation. In recent years, with the evolution of nanotechnology, nano-sized graphene and graphene derivatives have been frequently introduced into the construction of biosensors due to their unique physicochemical properties and biocompatibility. The combination of biomolecules with specific recognition capabilities and graphene materials provides a promising strategy to construct more stable and sensitive biosensors for the detection of pathogens. This review tracks the development of graphene biosensors for the detection of bacterial and viral pathogens, mainly including the preparation of graphene biosensors and their working mechanism. The challenges involved in this field have been discussed, and the perspective for further development has been put forward, aiming to promote the development of pathogens sensing and the contribution to epidemic prevention.


Subject(s)
Bacteria/isolation & purification , Betacoronavirus/isolation & purification , Biosensing Techniques/methods , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Graphite , Pandemics , Pneumonia, Viral/diagnosis , Viruses/isolation & purification , Animals , Bacteria/genetics , Bacteria/pathogenicity , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Testing , Graphite/chemistry , Humans , Molecular Diagnostic Techniques , Nanotechnology , SARS-CoV-2 , Viruses/genetics , Viruses/pathogenicity
12.
J Med Internet Res ; 22(6): e19782, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-605125

ABSTRACT

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, engagement in preventive behaviors and getting tested for the virus play a crucial role in protecting people from contracting the new coronavirus. OBJECTIVE: This study aims to examine how internet use, risk awareness, and demographic characteristics are associated with engagement in preventative behaviors and testing during the COVID-19 pandemic in the United States. METHODS: A cross-sectional survey was conducted on Amazon Mechanical Turk from April 10, 2020, to April 14, 2020. Participants' internet use (in terms of the extent of receiving information pertaining to COVID-19), risk awareness (whether any immediate family members, close friends or relatives, or people in local communities tested positive for COVID-19), demographics (sex, age, ethnicity, income, education level, marital status, and employment status), as well as their engagement in preventative behaviors and testing were assessed. RESULTS: Our data included 979 valid responses from the United States. Participants who received more COVID-19-related health information online reported more frequent effort to engage in all types of preventive behaviors: wearing a facemask in public (odds ratio [OR] 1.55, 95% CI 1.34-1.79, P<.001), washing hands (OR 1.58, 95% CI 1.35-1.85, P<.001), covering nose and mouth when sneezing and coughing (OR 1.78, 95% CI 1.52-2.10, P<.001), keeping social distance with others (OR 1.41, 95% CI 1.21-1.65, P<.001), staying home (OR 1.40, 95% CI 1.20-1.62, P<.001), avoiding using public transportation (OR 1.57, 95% CI 1.32-1.88, P<.001), and cleaning frequently used surfaces (OR 1.55, 95% CI 1.34-1.79, P<.001). Compared with participants who did not have positive cases in their social circles, those who had immediate family members (OR 1.48, 95% CI 8.28-26.44, P<.001) or close friends and relatives (OR 2.52, 95% CI 1.58-4.03, P<.001) who tested positive were more likely to get tested. Participants' sex, age, ethnicity, marital status, and employment status were also associated with preventive behaviors and testing. CONCLUSIONS: Our findings revealed that the extent of receiving COVID-19-related information online, risk awareness, and demographic characteristics including sex, ethnicity, age, marital status, and employment status are key factors associated with US residents' engagement in various preventive behaviors and testing for COVID-19.


Subject(s)
Coronavirus Infections/prevention & control , Coronavirus Infections/psychology , Internet , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/psychology , Risk Reduction Behavior , Adolescent , Adult , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Risk Factors , SARS-CoV-2 , Surveys and Questionnaires , United States/epidemiology , Young Adult
13.
J Med Internet Res ; 22(5): e19421, 2020 May 28.
Article in English | MEDLINE | ID: covidwho-401450

ABSTRACT

BACKGROUND: Coronavirus disease (COVID-19) has affected more than 200 countries and territories worldwide. This disease poses an extraordinary challenge for public health systems because screening and surveillance capacity is often severely limited, especially during the beginning of the outbreak; this can fuel the outbreak, as many patients can unknowingly infect other people. OBJECTIVE: The aim of this study was to collect and analyze posts related to COVID-19 on Weibo, a popular Twitter-like social media site in China. To our knowledge, this infoveillance study employs the largest, most comprehensive, and most fine-grained social media data to date to predict COVID-19 case counts in mainland China. METHODS: We built a Weibo user pool of 250 million people, approximately half the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19-related posts from our user pool from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify "sick posts," in which users report their own or other people's symptoms and diagnoses related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. RESULTS: We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China regardless of the unequal distribution of health care resources and the outbreak timeline. CONCLUSIONS: Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. In addition to monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understanding of information sharing behaviors is a promising approach to identify true disease signals and improve the effectiveness of infoveillance.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Public Health Surveillance , Public Health/methods , Social Media/statistics & numerical data , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/physiopathology , Disease Outbreaks/statistics & numerical data , Humans , Information Dissemination , Pandemics , Pneumonia, Viral/physiopathology , SARS-CoV-2
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