Brequinar and dipyridamole in combination exhibits synergistic antiviral activity against SARS-CoV-2 in vitro: Rationale for a host-acting antiviral treatment strategy for COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the associated global pandemic resulting in >400 million infections worldwide and several million deaths. The continued evolution of SARS-CoV-2 to potentially evade vaccines and monoclonal antibody (mAb)-based therapies and the limited number of authorized small-molecule antivirals necessitates the need for development of new drug treatments. There remains an unmet medical need for effective and convenient treatment options for SARS-CoV-2 infection. SARS-CoV-2 is an RNA virus that depends on host intracellular ribonucleotide pools for its replication. Dihydroorotate dehydrogenase (DHODH) is a ubiquitous host enzyme that is required for de novo pyrimidine synthesis. The inhibition of DHODH leads to a depletion of intracellular pyrimidines, thereby impacting viral replication in vitro. Brequinar (BRQ) is an orally available, selective, and potent low nanomolar inhibitor of human DHODH that has been shown to exhibit broad spectrum inhibition of RNA virus replication. However, host cell nucleotide salvage pathways can maintain intracellular pyrimidine levels and compensate for BRQ-mediated DHODH inhibition. In this report, we show that the combination of BRQ and the salvage pathway inhibitor dipyridamole (DPY) exhibits strong synergistic antiviral activity in vitro against SARS-CoV-2 by enhanced depletion of the cellular pyrimidine nucleotide pool. The combination of BRQ and DPY showed antiviral activity against the prototype SARS-CoV-2 as well as the Beta (B.1.351) and Delta (B.1.617.2) variants. These data support the continued evaluation of the combination of BRQ and DPY as a broad-spectrum, host-acting antiviral strategy to treat SARS-CoV-2 and potentially other RNA virus infections.

Factors Associated with Mental Health among International Students during the COVID-19 Pandemic in South Korea.

The purpose of this study was to investigate mental health problems among international students in South Korean universities during the COVID-19 pandemic, as well as to identify the factors that affect their mental health. A total of 488 international students living in South Korea participated in a web-based survey. The questionnaire was created using the Google Forms platform, and a link to the questionnaire was shared through social media. Multiple logistic regression analysis was conducted to analyze the data. The prevalence rates of sleep problems, anxiety, and depression among international students were 47.1%, 39.6%, and 49%, respectively. The prevalence of mental health problems was higher among participants who were male, living with someone, residents of a rural area, and earning a higher income. The following variables were found to contribute to the prevalence of mental health problems: undergraduate student status, good understanding of the Korean language, longer hours of media usage, and experiences related to COVID-19 infection. A collaborative effort between the government and universities to manage the mental health of international students could promote the mental health of these students.

COVID-19 Impact on Residential Preferences in the Early-Stage Outbreak in South Korea.

In the early stage of the COVID-19 pandemic in South Korea, public fear or social scaring of urban living was observed, which caused people to change their daily routines. This study examines how the COVID-19 pandemic affected residential choice and perceptions of urban living. We analyzed self-reported survey data collected from 2000 participants in Seoul, Daegu, and Kyeongbuk in South Korea between 3-6 August 2020, targeting the relatively controlled period after the first COVID-19 outbreak. Logistic regression models were used to examine concerns of urban living and residence relocation consideration. Those who were aged 30 or older, regularly commuting, not feeling healthy, with a household size of two, and living in a low-rise condominium were more likely to be concerned with urban living. Those who were aged 40 or older and living in a townhouse or a single-detached house were more likely to consider moving to a less dense area. People perceived that their daily routine changed substantially after the pandemic. Certain participant groups showed concerns of urban living and relocation consideration, suggesting housing policy implications.

A Comparison of Faculty and Student Acceptance Behavior toward Learning Management Systems.

During the COVID-19 pandemic, learning management systems have become the primary channel for lecturing and learning in higher education contexts. The present study investigates the development of user acceptance behavior toward a learning management system through use of the extended technology acceptance model. Moreover, this research identified differences between faculty and student behavior in a university environment. Based on a quantitative approach, the analysis results revealed that the main triggers of user acceptance behavior are self-efficacy, enjoyment, and computer anxiety. This study also documented the different influencing factors between faculty members and student groups, respectively. This work is expected to add to existing knowledge and help guide those working in higher education settings to establish more effective strategies for the optimization of learning management systems.