HIF-1α Pathway in COVID-19: A Scoping Review of Its Modulation and Related Treatments

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4202 - 4202

Published: April 28, 2025

The COVID-19 pandemic, driven by SARS-CoV-2, has led to a global health crisis, highlighting the virus's unique molecular mechanisms that distinguish it from other respiratory pathogens. It is known Hypoxia-Inducible Factor 1α (HIF-1α) activates complex network of intracellular signaling pathways regulating cellular energy metabolism, angiogenesis, and cell survival, contributing wide range clinical manifestations COVID-19, including Post-Acute Syndrome (PACS). Emerging evidence suggests dysregulation HIF-1α key driver systemic inflammation, silent hypoxia, pathological tissue remodeling in both acute post-acute phases disease. This scoping review was conducted following PRISMA-ScR guidelines registered INPLASY. involved literature search Scopus PubMed, supplemented manual reference screening, with study selection facilitated Rayyan software. Our analysis clarifies dual role HIF-1α, which may either worsen inflammatory responses viral persistence or support adaptive reduce damage. potential for targeting therapeutically complex, requiring further investigation clarify its precise translational applications. deepens understanding SARS-CoV-2-induced dysfunction offering insights improving management strategies addressing long-term sequelae.

Language: Английский

Oral pharmacokinetics and efficacy of oral phospholipid remdesivir nucleoside prodrugs against SARS-CoV-2 in mice

Antimicrobial Agents and Chemotherapy, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

ABSTRACT Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1- O -octadecyl-2- -benzyl- sn -glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug GS-441524 (remdesivir nucleoside, RVn), demonstrated its in vivo efficacy SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) 4-cyano-benzyl (V2067), that significantly enhanced vitro antiviral activity against multiple viruses when compared to V2043. Here, we demonstrate V2043, V2053, V2067 all orally bioavailable, well-tolerated, achieve high sustained plasma levels after single oral daily dosing. All three prodrugs more active than RVn reduce lung titers prophylaxis models B.1.351 infection. On molar basis, V2043 substantially obeldesivir/GS-5245 molnupiravir . Together, these data support continued development other clinical concern.

Language: Английский

Pyronaridine Inhibited MUC5AC Mucin Gene Expression by Regulation of Nuclear Factor Kappa B Signaling Pathway in Human Pulmonary Mucoepidermoid Cells

Biomolecules & Therapeutics, Journal Year: 2024, Volume and Issue: 32(5), P. 540 - 545

Published: Aug. 2, 2024

In this study, the potential effects of pyronaridine, an antimalarial agent, on airway MUC5AC mucin gene expression were investigated.The human pulmonary epithelial NCI-H292 cells pretreated with pyronaridine for 30 min and then stimulated phorbol 12-myristate 13-acetate (PMA) 24 h.The effect PMA-induced nuclear factor kappa B (NF-κB) signaling pathway was also examined.Pyronaridine inhibited glycoprotein production mRNA mucins induced by PMA through inhibition degradation inhibitory Bα NF-κB p65 translocation.These results suggest that suppresses regulation in cells.

Language: Английский