Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 14, 2023

The coronavirus disease 2019 (COVID-19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that rapidly evolving subvariants risk rendering vaccines antibodies ineffective due to their potential evade existing immunity, with enhanced transmission activity higher reinfection rates could lead new outbreaks across globe. goal viral management is disrupt life cycle as well relieve severe symptoms such lung damage, cytokine storm, organ failure. In fight against viruses, combination genome sequencing, elucidation structure proteins, identifying proteins are highly conserved multiple coronaviruses revealed many molecular targets. addition, time- cost-effective repurposing preexisting antiviral drugs or approved/clinical for these targets offers considerable clinical advantages COVID-19 patients. This review provides comprehensive overview various identified pathogenic pathways corresponding repurposed COVID-19. These findings provide insight into discovery novel therapeutic strategies be applied control emanating from SARS-CoV-2 variants.

Language: Английский

Mechanistic insights into SARS-CoV-2 spike protein induction of the chemokine CXCL10

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 16, 2024

During a SARS-CoV-2 infection, macrophages recognize viral components resulting in cytokine production. While this response fuels virus elimination, overexpression of cytokines can lead to severe COVID-19. Previous studies suggest that the spike protein (S) elicit production via transcription factor NF-κB and toll-like receptors (TLRs). In study, we found that: (i) S S2 subunit induce CXCL10, chemokine implicated COVID-19, gene expression by human macrophage cells (THP-1); (ii) glycogen synthase kinase-3 inhibitor attenuates induction; (iii) do not activate but IRF; (iv) require TLR2 CXCL10 or (v) peripheral blood mononuclear (PBMCs). We also discovered cellular response, lack thereof, is function recombinant used. such finding raises possibility confounding LPS contamination, offer evidence potential contaminating does underly induced increases CXCL10. Combined, these results provide insights into complex immune possible therapeutic targets for

Language: Английский

Capturing the Effects of Single Atom Substitutions on the Inhibition Efficiency of Glycogen Synthase Kinase-3β Inhibitors via Markov State Modeling and Experiments

Journal of Chemical Theory and Computation, Journal Year: 2024, Volume and Issue: 20(14), P. 6278 - 6286

Published: July 8, 2024

Small modifications in the chemical structure of ligands are known to dramatically change their ability inhibit activity a protein. Unraveling mechanisms that govern these dramatic changes requires scrutinizing dynamics protein-ligand binding and unbinding at atomic level. As an exemplary case, we have studied Glycogen Synthase Kinase-3β (GSK-3β), multifunctional kinase has been implicated host pathological processes. such, there is keen interest identifying GSK-3β activity. One family compounds highly selective potent inhibitors exemplified by molecule termed COB-187. COB-187 consists five-member heterocyclic ring with thione C

Language: Английский