The most advanced antiviral molecules addressing major SARS-CoV-2 targets (Main protease, Spike protein, and RNA polymerase), compared with proteins of other human pathogenic coronaviruses, may have a short-lasting clinical efficacy. Accumulating knowledge on the mechanisms underlying the target structural basis, its mutational progression, and the related biological significance to virus replication allows envisaging the development of better-targeted therapies in the context of COVID-19 epidemic and future coronavirus outbreaks. The identification of evolutionary patterns based solely on sequence information analysis for those targets can provide meaningful insights into the molecular basis of host-pathogen interactions and adaptation, leading to drug resistance phenomena. Herein, we will explore how the study of observed and predicted mutations may offer valuable suggestions for the application of the so-called "synthetic lethal" strategy to SARS-CoV-2 Main protease and Spike protein. The synergy between genetics evidence and drug discovery may prioritize the development of novel long-lasting antiviral agents.
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http://dx.doi.org/10.1021/acs.jmedchem.2c01229 | DOI Listing |
RSC Adv
January 2025
Jiangsu Key Laboratory of Sericultural Biology and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology Zhenjiang 212100 China
: in the twenty-first century, the emergence of COVID-19 as a highly transmissible pandemic disease caused by SARS-CoV-2 posed a significant threat to humanity. : the disease spreads through small respiratory droplets, necessitating the use of various compounds for treatment, with alkaloids being recognized as particularly crucial owing to their diverse pharmaceutical properties. : in this study, a dataset comprising 100 natural alkaloids obtained from the literature was transformed into 2D chemical structures using Chem Draw 19.
View Article and Find Full Text PDFBMC Neurol
January 2025
Department of Neurology, RWTH Aachen University, Pauwels Street 30, Aachen, 52074, Germany.
Background: The definition of minor ischemic stroke (MIS) is a topic of debate, however, the most accepted definition is a stroke with National Institutes of Health Stroke Scale (NIHSS) ≤ 5. Intravenous thrombolysis (IVT) is a crucial treatment option for acute ischemic stroke (AIS) including: alteplase, recombinant human tissue-type plasminogen activator (r-tPA), and the recently approved tenecteplase. However, there is a debate regarding its safety and efficacy.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, 59064-741, RN, Brazil.
The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a major challenge to global health. Targeting the main protease of the virus (Mpro), which is essential for viral replication and transcription, offers a promising approach for therapeutic intervention. In this study, advanced computational techniques such as molecular docking and molecular dynamics simulations were used to screen a series of antiviral compounds for their potential inhibitory effect on the SARS-CoV-2 Mpro.
View Article and Find Full Text PDFBiofactors
January 2025
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Intracellular proteins take part in almost every body function; thus, protein homeostasis is of utmost importance. The ubiquitin proteasome system (UPS) has a fundamental role in protein homeostasis. Its main role is to selectively eradicate impaired or misfolded proteins, thus halting any damage that could arise from the accumulation of these malfunctioning proteins.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Molecular Genetics and Infection Biology, University of Greifswald, 17489, Greifswald, Germany.
In recent years, increased numbers of severe Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections, including necrotizing soft tissue infections (NSTIs), have been reported. One of the main virulence factors of SDSE is streptokinase (Ska).
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