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1.
Hum Behav Emerg Technol ; 2(3): 200-211, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1898740

ABSTRACT

Since the outbreak in China in late 2019, the novel coronavirus (COVID-19) has spread around the world and has come to dominate online conversations. By linking 2.3 million Twitter users to locations within the United States, we study in aggregate how political characteristics of the locations affect the evolution of online discussions about COVID-19. We show that COVID-19 chatter in the United States is largely shaped by political polarization. Partisanship correlates with sentiment toward government measures and the tendency to share health and prevention messaging. Cross-ideological interactions are modulated by user segregation and polarized network structure. We also observe a correlation between user engagement with topics related to public health and the varying impact of the disease outbreak in different U.S. states. These findings may help inform policies both online and offline. Decision-makers may calibrate their use of online platforms to measure the effectiveness of public health campaigns, and to monitor the reception of national and state-level policies, by tracking in real-time discussions in a highly polarized social media ecosystem.

2.
JMIR Infodemiology ; 2(1): e32378, 2022.
Article in English | MEDLINE | ID: covidwho-1707944

ABSTRACT

BACKGROUND: The novel coronavirus, also known as SARS-CoV-2, has come to define much of our lives since the beginning of 2020. During this time, countries around the world imposed lockdowns and social distancing measures. The physical movements of people ground to a halt, while their online interactions increased as they turned to engaging with each other virtually. As the means of communication shifted online, information consumption also shifted online. Governing authorities and health agencies have intentionally shifted their focus to use social media and online platforms to spread factual and timely information. However, this has also opened the gate for misinformation, contributing to and accelerating the phenomenon of misinfodemics. OBJECTIVE: We carried out an analysis of Twitter discourse on over 1 billion tweets related to COVID-19 over a year to identify and investigate prevalent misinformation narratives and trends. We also aimed to describe the Twitter audience that is more susceptible to health-related misinformation and the network mechanisms driving misinfodemics. METHODS: We leveraged a data set that we collected and made public, which contained over 1 billion tweets related to COVID-19 between January 2020 and April 2021. We created a subset of this larger data set by isolating tweets that included URLs with domains that had been identified by Media Bias/Fact Check as being prone to questionable and misinformation content. By leveraging clustering and topic modeling techniques, we identified major narratives, including health misinformation and conspiracies, which were present within this subset of tweets. RESULTS: Our focus was on a subset of 12,689,165 tweets that we determined were representative of COVID-19 misinformation narratives in our full data set. When analyzing tweets that shared content from domains known to be questionable or that promoted misinformation, we found that a few key misinformation narratives emerged about hydroxychloroquine and alternative medicines, US officials and governing agencies, and COVID-19 prevention measures. We further analyzed the misinformation retweet network and found that users who shared both questionable and conspiracy-related content were clustered more closely in the network than others, supporting the hypothesis that echo chambers can contribute to the spread of health misinfodemics. CONCLUSIONS: We presented a summary and analysis of the major misinformation discourse surrounding COVID-19 and those who promoted and engaged with it. While misinformation is not limited to social media platforms, we hope that our insights, particularly pertaining to health-related emergencies, will help pave the way for computational infodemiology to inform health surveillance and interventions.

3.
SLAS Discov ; 27(1): 8-19, 2022 01.
Article in English | MEDLINE | ID: covidwho-1641663

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Cysteine Proteinase Inhibitors/pharmacology , Dipeptides/pharmacology , Virus Attachment/drug effects , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cathepsin L/antagonists & inhibitors , Cell Line , Chlorocebus aethiops , Drug Evaluation, Preclinical , Drug Repositioning , HEK293 Cells , Humans , Molecular Docking Simulation , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
4.
Nat Commun ; 12(1): 6055, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1475294

ABSTRACT

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/administration & dosage , Indoles/administration & dosage , Leucine/administration & dosage , Pyrrolidinones/administration & dosage , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacokinetics , Alanine/administration & dosage , Alanine/adverse effects , Alanine/analogs & derivatives , Alanine/pharmacokinetics , Animals , COVID-19/virology , Chlorocebus aethiops , Coronavirus 229E, Human/drug effects , Coronavirus 229E, Human/enzymology , Coronavirus Protease Inhibitors/adverse effects , Coronavirus Protease Inhibitors/pharmacokinetics , Disease Models, Animal , Drug Design , Drug Synergism , Drug Therapy, Combination , HeLa Cells , Humans , Indoles/adverse effects , Indoles/pharmacokinetics , Infusions, Intravenous , Leucine/adverse effects , Leucine/pharmacokinetics , Mice , Pyrrolidinones/adverse effects , Pyrrolidinones/pharmacokinetics , SARS Virus/drug effects , SARS Virus/enzymology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Vero Cells
5.
JCO Oncol Pract ; 18(1): e89-e97, 2022 01.
Article in English | MEDLINE | ID: covidwho-1331970

ABSTRACT

PURPOSE: The COVID-19 pandemic has created a new set of problems for clinicians. This study examines the experiences of oncologists providing care to seriously ill persons near the end of life in the context of the COVID-19 pandemic. METHODS: Between January 2020 and August 2020, we conducted semistructured, in-depth individual interviews with 22 purposefully sampled oncologists from practices enrolled in the Michigan Oncology Quality Consortium. Deidentified transcripts of the interviews were examined using thematic analysis. RESULTS: Our respondents described several novel problems created by the COVID-19 pandemic, including: (1) ethical challenges, (2) the need to manage uncertainty-physically and emotionally-on the part of both patients and oncologists, and (3) the difficulty of integrating technology and communication for seriously ill persons. These problems were made more complex by features of the pandemic: resource scarcity (and the need to fairly allocate poor resources), delays in care, high levels of fear, and the increased importance of advance care planning. Nonabandonment served as a way to cope with increased stress, and the use of telemedicine became an increasingly important medium of communication. CONCLUSION: This study offers an in-depth exploration of the problems faced by oncologists as a result of the COVID-19 pandemic and how they navigated them. Optimal decision making for seriously ill persons with cancer during the COVID-19 pandemic must include open acknowledgment of the ethical challenges involved, the emotions experienced by both patients and their oncologists, and the urgent need to integrate technology with compassionate communication in determining patient preferences.


Subject(s)
COVID-19 , Oncologists , Communication , Empathy , Humans , Pandemics , Prognosis , SARS-CoV-2
6.
J Med Internet Res ; 23(6): e26692, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1285240

ABSTRACT

BACKGROUND: The novel coronavirus pandemic continues to ravage communities across the United States. Opinion surveys identified the importance of political ideology in shaping perceptions of the pandemic and compliance with preventive measures. OBJECTIVE: The aim of this study was to measure political partisanship and antiscience attitudes in the discussions about the pandemic on social media, as well as their geographic and temporal distributions. METHODS: We analyzed a large set of tweets from Twitter related to the pandemic, collected between January and May 2020, and developed methods to classify the ideological alignment of users along the moderacy (hardline vs moderate), political (liberal vs conservative), and science (antiscience vs proscience) dimensions. RESULTS: We found a significant correlation in polarized views along the science and political dimensions. Moreover, politically moderate users were more aligned with proscience views, while hardline users were more aligned with antiscience views. Contrary to expectations, we did not find that polarization grew over time; instead, we saw increasing activity by moderate proscience users. We also show that antiscience conservatives in the United States tended to tweet from the southern and northwestern states, while antiscience moderates tended to tweet from the western states. The proportion of antiscience conservatives was found to correlate with COVID-19 cases. CONCLUSIONS: Our findings shed light on the multidimensional nature of polarization and the feasibility of tracking polarized opinions about the pandemic across time and space through social media data.


Subject(s)
COVID-19/therapy , Social Media/trends , Humans , Internet Use , Politics , SARS-CoV-2 , Telemedicine
7.
Nat Commun ; 12(1): 3309, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1260940

ABSTRACT

The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Repositioning/methods , Pandemics , SARS-CoV-2 , Animals , COVID-19/prevention & control , COVID-19/virology , Cell Line , Cytidine/administration & dosage , Cytidine/analogs & derivatives , Cytidine/pharmacology , Databases, Pharmaceutical , Drug Discovery/methods , Drug Evaluation, Preclinical/methods , HeLa Cells , High-Throughput Screening Assays/methods , Humans , Hydroxylamines/administration & dosage , Hydroxylamines/pharmacology , Mesocricetus , Nelfinavir/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Virus Replication/drug effects
8.
9.
SLAS Discov ; 25(10): 1152-1161, 2020 12.
Article in English | MEDLINE | ID: covidwho-846185

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 has triggered an ongoing global pandemic whereby infection may result in a lethal severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, millions of confirmed cases and hundreds of thousands of deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. The purported development of a vaccine could require at least 1-4 years, while the typical timeline from hit finding to drug registration of an antiviral is >10 years. Thus, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we developed and initiated a high-throughput cell-based screen that incorporates the essential viral papain-like protease (PLpro) and its peptide cleavage site into a luciferase complementation assay to evaluate the efficacy of known drugs encompassing approximately 15,000 clinical-stage or US Food and Drug Administration (FDA)-approved small molecules. Confirmed inhibitors were also tested to determine their cytotoxic properties. Here, we report the identification of four clinically relevant drugs that exhibit selective inhibition of the SARS-CoV-2 viral PLpro.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , High-Throughput Screening Assays/methods , Protease Inhibitors/pharmacology , Bleomycin/pharmacology , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , HEK293 Cells , Humans , Papain/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology
10.
J Dent Educ ; 2020 Jul 19.
Article in English | MEDLINE | ID: covidwho-657574
11.
J Dent Educ ; 2020 Jul 15.
Article in English | MEDLINE | ID: covidwho-645285
12.
JMIR Public Health Surveill ; 2020.
Article | WHO COVID | ID: covidwho-333044

ABSTRACT

BACKGROUND: At the time of this writing, the novel coronavirus (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much conversation about these phenomena now occurs online, e.g., on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual coronavirus (COVID-19) Twitter dataset that we are making available to the research community via our COVID-19-TweetIDs Github repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter's Streaming API and Tweepy to follow certain keywords and accounts that were trending at the time the collection began, and used Twitter's Search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our Github repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This manuscript also presents basic analysis that shows that Twitter activity responds and reacts to coronavirus-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This dataset could also help track scientific coronavirus misinformation and unverified rumors or enable the understanding of fear and panic - and undoubtedly more. CLINICALTRIAL:

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