Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdańsk, 80-308 Gdańsk, Poland.
Published: April 2023
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Article Abstract
Furin is a human serine protease responsible for activating numerous physiologically relevant cell substrates and is also involved in the development of various pathological conditions, including inflammatory diseases, cancers, and viral and bacterial infections. Therefore, compounds with the ability to inhibit furin's proteolytic action are regarded as potential therapeutics. Here we took the combinatorial chemistry approach (library consisting of 2000 peptides) to obtain new, strong, and stable peptide furin inhibitors. The extensively studied trypsin inhibitor SFTI-1 was used as a leading structure. A selected monocylic inhibitor was further modified to finally yield five mono- or bicyclic furin inhibitors with values of in the subnanomolar range. Inhibitor was the most active ( = 0.21 nM) and significantly more proteolytically resistant than the reference furin inhibitor described in the literature. Moreover, it reduced furin-like activity in PANC-1 cell lysate. Detailed analysis of furin-inhibitor complexes using molecular dynamics simulations is also reported.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains.
Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei, Taiwan; Taichung Armed Forces General Hospital, Taichung, Taiwan. Electronic address:
Background: Cardiac remodeling is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure, and cardiac arrhythmias. Nuclear factor-activated T-cell cytoplasmic (NFATc) is a crucial transcription factor that regulates cardiac remodeling. MicroRNA (miR)-424/322 has pathophysiological roles in the cardiovascular and respiratory systems by modulating hypoxia and inflammatory pathways.
Key Laboratory of Screening and Control of Infectious Diseases, Fujian Provincial University, Quanzhou Medical College, Quanzhou, 362011, Fujian, China.
The PI3K/Akt pathway is overexpressed in nearly 50% of hepatocellular carcinomas and inhibits apoptosis by promoting the expression of antiapoptotic genes. Serine protease inhibitors have been shown to induce apoptosis in hepatoma cells by downregulating SPINK13 in the PI3K/Akt pathway. In this study, SPINK13 was expressed in lentiviral vectors.
Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing 400016, China. Electronic address:
The study investigates the natural compound diphyllin's effectiveness against SARS-CoV-2, the virus responsible for COVID-19, particularly against various variants like Alpha, Beta, Delta, and Omicron.
Results show that diphyllin inhibits the virus's entry into cells in a dose-dependent manner by disrupting critical processes required for viral entry.
The research highlights diphyllin's potential as a dual-action antiviral agent by targeting both endosomal and cell surface pathways involved in SARS-CoV-2 entry.
Human parainfluenza virus 3 (HPIV3) infection relies on the combined actions of the hemagglutinin-neuraminidase (HN) and fusion protein (F) to facilitate virus-cell membrane fusion for infection.
Unlike laboratory-adapted strains, field strains of HPIV3 have different cleavage motifs for the F protein, which are cleaved by specific, unidentified proteases found in limited cell types.
The study highlights that extracellular serine proteases, like TMPRSS2 and TMPRSS13, can activate the F protein for infectious virus release, suggesting that the activation process depends on the availability of these proteases in host cells.
