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Structure-Based Discovery of the SARS-CoV-2 Main Protease Noncovalent Inhibitors from Traditional Chinese Medicine
Traditional Chinese medicine (TCM) has been extensively employed for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is demand for discovering more SARS-CoV-2 Mpro inhibitors with diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this study, comprehensive in silico and in vitro assays were utilized to determine the potential inhibitors from TCM compounds against SARS-CoV-2 Mpro, which is an important therapeutic target for SARS-CoV-2. The ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2 Mpro conformations identified 19 TCM compounds as promising candidates. Further in vitro testing validated three compounds as inhibitors of SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11, 7.56 ± 0.78, and 11.16 ± 0.26 μM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ± 1.25 μM, respectively. Molecular dynamics (MD) simulations indicated that the three complexes remained stable over the last 100 ns of production run. An analysis of the binding mode revealed that the active compounds occupy different subsites (S1, S2, S3, and S4) of the active site of SARS-CoV-2 Mpro via specific poses through noncovalent interactions with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU 166, or GLN 189). Overall, this study provides evidence indicating that the three natural products obtained from TCM could be further used for anti-COVID-19 research, justifying the investigation of Chinese herbal medicinal ingredients as bioactive constituents for therapeutic targets.
期刊论文
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Integration of text messaging intervention into hypertension management among older adults: A systematic review and meta-analysis
BACKGROUND: An aging population and required hypertension control are global concerns that burden the healthcare system. Text messaging interventions have been developed to support hypertension management, but their effects on the older population are unknown. OBJECTIVES: This review aimed to identify the effects of a text messaging intervention on hypertension management among older adults. METHODS: Four English and two Chinese databases with randomized controlled trials published between January 2010 and December 2020 were searched. The mean age of the participants was 60 years or above. Participants were also diagnosed with hypertension. The Cochrane risk-of-bias tool was used for the critical appraisal. Data in each study were extracted, and a meta-analysis was presented in terms of mean difference (MD) and standardized mean difference (SMD). RESULTS: A total of 1670 records were screened, of which six were included in the final review. The intervention of the included studies lasted up to 6 months, and one-way text messaging was commonly used. Meta-analysis showed that a text messaging intervention significantly reduced systolic blood pressure (MD = -6.11, p < .01) but not diastolic blood pressure. Regarding medication adherence, a moderate effect was noted with the use of text messaging among older adults with hypertension (SMD = 0.65, p = .01). LINKING EVIDENCE TO ACTION: A text messaging intervention can improve hypertension management among older adults. The standardized content of one-way text messaging is suggested to be delivered weekly.
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An Organizational Readiness Intervention and Randomized Controlled Trial to Test Strategies for Implementing Substance Use Disorder Treatment Into Primary Care: SUMMIT Study Protocol
BACKGROUND: Millions of people who need treatment for substance use disorders (SUD) do not receive it. Evidence-based practices for treating SUD exist, and some are appropriate for delivery outside of specialty care settings. Primary care is an opportune setting in which to deliver SUD treatment because many individuals see their primary care providers at least once a year. Further, the Patient Protection and Affordable Care Act (PPACA) increases coverage for SUD treatment and is increasing the number of individuals seeking primary care services. In this article, we present the protocol for a study testing the effects of an organizational readiness and service delivery intervention on increasing the uptake of SUD treatment in primary care and on patient outcomes. METHODS/DESIGN: In a randomized controlled trial, we test the combined effects of an organizational readiness intervention consisting of implementation tools and activities and an integrated collaborative care service delivery intervention based on the Chronic Care Model on service system (patient-centered care, utilization of substance use disorder treatment, utilization of health care services and adoption and sustainability of evidence-based practices) and patient (substance use, consequences of use, health and mental health, and satisfaction with care) outcomes. We also use a repeated measures design to test organizational changes throughout the study, such as acceptability, appropriateness and feasibility of the practices to providers, and provider intention to adopt the practices. We use provider focus groups, provider and patient surveys, and administrative data to measure outcomes. DISCUSSION: The present study responds to critical gaps in health care services for people with substance use disorders, including the need for greater access to SUD treatment and greater uptake of evidence-based practices in primary care. We designed a multi-level study that combines implementation tools to increase organizational readiness to adopt and sustain evidence-based practices (EBPs) and tests the effectiveness of a service delivery intervention on service system and patient outcomes related to SUD services.
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