Acellular Human Amniotic Fluid-Derived Extracellular Vesicles as Novel Anti-Inflammatory Therapeutics against SARS-CoV-2 Infection.

Publication date: Feb 09, 2024

The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. However, despite strong evidence for the role of virus-induced inflammation in severe COVID-19, no effective anti-inflammatory drug is available to control fatal inflammation as well as efficiently clear the virus. Therefore, there is an urgent need to identify biologically derived immunomodulators that suppress inflammation and promote antiviral immunity. In this study, we evaluated acellular human amniotic fluid (acAF) containing extracellular vesicles (hAF-EVs) as a potential non-toxic and safe biologic for immunomodulation during COVID-19. Our in vitro results showed that acAF significantly reduced inflammatory cytokine production in TLR2/4/7 and SARS-CoV-2 structural protein-stimulated mouse macrophages. Importantly, an intraperitoneal administration of acAF reduced morbidity and mortality in SARS-CoV-2-infected mice. A detailed examination of SARS-CoV-2-infected lungs revealed that the increased protection in acAF-treated mice was associated with reduced viral titers and levels of inflammatory myeloid cell infiltration. Collectively, our results identify a novel biologic that has potential to suppress excessive inflammation and enhance survival following SARS-CoV-2 infection, highlighting the translational potential of acAF against COVID-19.

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Concepts Keywords
Immunomodulation acAF
Lethal AF-EVs
Mice Amniotic Fluid
Myeloid Animals
Pneumonia Anti-Inflammatory Agents
Anti-Inflammatory Agents
Biological Products
Biological Products
COVID-19
cytokine storm
dysregulated immunity
Extracellular Vesicles
Humans
Inflammation
MA-CoV-2
Mice
myeloid cells
Pandemics
Respiratory Distress Syndrome
SARS-CoV-2

Semantics

Type Source Name
disease MESH SARS-CoV-2 Infection
pathway REACTOME SARS-CoV-2 Infection
disease MESH acute respiratory distress syndrome
disease MESH pneumonia
disease MESH inflammation
disease IDO replication
disease VO effective
disease VO intraperitoneal administration
disease MESH morbidity
disease IDO cell
disease VO USA
drug DRUGBANK Coenzyme M
disease MESH syndrome
disease MESH cytokine storm
disease VO Severe acute respiratory syndrome coronavirus 2
disease VO population
disease MESH lung injury
disease MESH melanoma
pathway KEGG Melanoma
disease IDO host
disease MESH emergency
drug DRUGBANK Ritonavir
disease MESH infection
drug DRUGBANK Tocilizumab
drug DRUGBANK Anakinra
drug DRUGBANK Baricitinib
drug DRUGBANK Dexamethasone
drug DRUGBANK Spinosad
drug DRUGBANK Thioredoxin
pathway KEGG Viral replication
drug DRUGBANK L-Glutamine
drug DRUGBANK Sodium bicarbonate
drug DRUGBANK Amino acids
disease IDO history
disease IDO assay
drug DRUGBANK Water
disease VO syringe
disease MESH Virus Infection
disease VO dose
disease VO titer
disease VO protocol
drug DRUGBANK Aspartame
drug DRUGBANK Phosphate ion
drug DRUGBANK Isoflurane
disease MESH weight loss
drug DRUGBANK Gentian violet cation
drug DRUGBANK Collagenase clostridium histolyticum
disease VO ANOVA
disease VO M protein
disease IDO production
disease VO time
disease VO URE
disease MESH complications
disease MESH death

Original Article

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