For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were proposed as potential inhibitors of the SARS-CoV-2 main viral protease (3-chymotrypsin-like, 3CLpro). Based on the created pharmacophore model of the active site of the protease, a group of compounds were modeled and tested for activity against 3CLpro. The 3CLpro activity was measured using the fluorogenic substrate Dabcyl-VNSTLQSGLRK(FAM)MA; the efficiency of the proposed approach was confirmed by comparison with literature data for ebselen and disulfiram. The results of the experiments performed with bispidine compounds showed that 14 compounds exhibited activity in the concentration range 1-10 μM, and 3 samples exhibited submicromolar activity. The structure-activity relationship studies showed that the molecules containing a carbonyl group in the ninth position of the bicycle exhibited the maximum activity. Based on the experimental and theoretical results obtained, further directions for the development of this topic were proposed.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491553 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.1c00299 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Telemedicine for HIV care: a cross-sectional survey of people living with HIV receiving care at two federally qualified health centers in Los Angeles during a mature phase of the COVID-19 pandemic.
BMC Infect Dis
December 2024
Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, US.
Background: The COVID-19 pandemic resulted in the rapid implementation of telemedicine for HIV care at federally qualified health centers (FQHCs) in the United States. We sought to understand use of telemedicine (telephone and video) at two FQHCs in Los Angeles, and the client attitudes towards and experiences with telemedicine as part of future HIV care.
Methods: We conducted surveys with 271 people living with HIV (PLHIV), with questions covering sociodemographic factors, telemedicine attitudes and experiences, technological literacy, and access to technological resources and privacy.
An isothermal calorimetry assay for determining steady state kinetic and Ensitrelvir inhibition parameters for SARS-CoV-2 3CL-protease.
Sci Rep
December 2024
Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, 40127, Bologna, Italy.
This manuscript details the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CL, the main protease from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CL is essential for producing the proteins necessary for viral infection, which led to the COVID-19 pandemic. The ITC-based assay provided rapid and reliable measurements of 3CL activity, allowing for the direct derivation of the kinetic enzymatic constants K and k by monitoring the thermal power required to maintain a constant temperature as the substrate is consumed.
View Article and Find Full Text PDFAdherence to implementing physical distancing and other COVID-19 preventive measures and its barriers among adults in Arba Minch town, Southwest Ethiopia: A lesson learned from the pandemic.
PLoS One
December 2024
MedStar Georgetown University Hospital, Washington, DC, United States of America.
Background: Globally, as of March 2024, the number of confirmed Coronavirus Disease 2019 (COVID-19) cases and deaths were over 774 million and seven million, respectively. Since there are no proven treatment in place against the disease, controlling strategy mainly rely on preventive measures. However, data on the extent of implementing physical distancing and other preventive measures during the pandemic of COVID-19 were inadequate in the study setting.
View Article and Find Full Text PDFManagement of intracranial and orbital complications of acute rhinosinusitis and acute otitis media in the post covid-19 era in pediatric patients.
Eur Arch Otorhinolaryngol
December 2024
Division of Neurosurgery, Department of Translational Biomedicine and Neurosciences (DiBraiN), University "Aldo Moro" of Bari, Bari, 70124, Italy.
Purpose: Acute bacterial rhinosinusitis (ABRS) and acute otitis media (AOM) are common diseases in pediatric populations that rarely lead to intracranial infection and/or orbital complications. The incidence of these complications has increased in recent years and the main aim of this study is to analyze the tendency of this increase during the pandemic years, compared with the pre-pandemic era and to propose our management of ABRS and AOM.
Method: Clinical data from children, admitted to our hospital during the period from January 2018 to March 2024 with a diagnosis of complicated ABRS and AOM was collected.
Design of an intelligent disinfection control system based on an STM32 single-chip microprocessor by using the YOLO algorithm.
Sci Rep
December 2024
College of Mechanical and Electronic Engineering, Dalian Minzu University, Dalian, 116650, Liaoning, China.
The novel coronavirus (COVID-19) has affected more than two million people of the world, and far social distancing and segregated lifestyle have to be adopted as a common solution in recent years. To solve the problem of sanitation control and epidemic prevention in public places, in this paper, an intelligent disinfection control system based on the STM32 single-chip microprocessor was designed to realize intelligent closed-loop disinfection in local public places such as public toilets. The proposed system comprises seven modules: image acquisition, spraying control, disinfectant liquid level control, access control, voice broadcast, system display, and data storage.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!