Differing activities of oxysterol-binding protein (OSBP) targeting anti-viral compounds

Roberts, Brett L; Severance, Zachary C; Bensen, Ryan C.; Le-McClain, Anh T.; Malinky, Cori A; Mettenbrink, Evan M.; Nuñez, Juan I; Reddig, William J; Blewett, Earl L.; Burgett, Anthony W. G.

doi:10.1016/j.antiviral.2019.104548

Cited by 36 publications

(50 citation statements)

References 37 publications

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“…Orsaponin (OSW-1) is a natural product extracted from the bulbs of the plant Ornithogalum saundersiae mainly employed in the anti-proliferative and anti-cancer activity [ 124 ]. Several studies demonstrated that OSW-1 binds to one of the two established OSBP ligand binding sites and induces prophylactic antiviral activity against all enteroviruses tested, enterovirus 71, coxsackievirus A21 and human rhinovirus 2 [ 125 , 126 ]. Antiviral protection is expressed through the reduction of intracellular levels of OSBP.…”

Section: Natural Compounds Against Rna Virusesmentioning

confidence: 99%

Antiviral Activity Exerted by Natural Products against Human Viruses

Musarra‐Pizzo

Pennisi

Ben-Amor

et al. 2021

Viruses

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Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease.

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Section: Natural Compounds Against Rna Virusesmentioning

confidence: 99%

Antiviral Activity Exerted by Natural Products against Human Viruses

Musarra‐Pizzo

Pennisi

Ben-Amor

et al. 2021

Viruses

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“…Several inhibitors targeting this enzyme have broad-spectrum activity in human cells and in mouse models of enterovirus infection [38,85,[104][105][106][107]. Likewise, OSBP, the protein important for PI4P/cholesterol flux, was shown to be inhibited by several potent antiviral compounds, further highlighting this pathway as a potential host-directed target [101,[108][109][110][111][112]. Enteroviruses can be selected with mutations that allow replication in PI4K knockout cells and in wild type cells treated with PI4K/OSBP targeting compounds [106,113,114].…”

Section: Creating the Optimal Lipid Microenvironment For Rna Replicationmentioning

confidence: 99%

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

Peters

Carette

2021

Viruses

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Enteroviruses are among the most common human infectious agents. While infections are often mild, the severe neuropathogenesis associated with recent outbreaks of emerging non-polio enteroviruses, such as EV-A71 and EV-D68, highlights their continuing threat to public health. In recent years, our understanding of how non-polio enteroviruses co-opt cellular pathways has greatly increased, revealing intricate host–virus relationships. In this review, we focus on newly identified mechanisms by which enteroviruses hijack the cellular machinery to promote their replication and spread, and address their potential for the development of host-directed therapeutics. Specifically, we discuss newly identified cellular receptors and their contribution to neurotropism and spread, host factors required for viral entry and replication, and recent insights into lipid acquisition and replication organelle biogenesis. The comprehensive knowledge of common cellular pathways required by enteroviruses could expose vulnerabilities amenable for host-directed therapeutics against a broad spectrum of enteroviruses. Since this will likely include newly arising strains, it will better prepare us for future epidemics. Moreover, identifying host proteins specific to neurovirulent strains may allow us to better understand factors contributing to the neurotropism of these viruses.

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“…Further studies have revealed that it is a powerful broad-spectrum antiviral medicine for Picornaviridae and enveloped viruses such as the influenza A virus [ 35 , 36 , 69 ]. Another natural compound, OSW-1 [3 beta, 16 beta, 17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1--> 3)-(2-O-acetyl-alpha-L-arabinopyranoside)], being a potent anticancer drug, is reported to inhibit OSBP in enterovirus and is assumed to be effective for SARS-CoV-2 [ 37 , 38 ].…”

Section: Targeting Virus Replicationmentioning

confidence: 99%

“…, being a potent anticancer drug, is reported to inhibit OSBP in enterovirus and is assumed to be effective for SARS-CoV-2 [37,38].…”

Section: Inhibitors Of Oxysterol-binding Proteinmentioning

confidence: 99%

Targeting Some Enzymes with Repurposing Approved Pharmaceutical Drugs for Expeditious Antiviral Approaches Against Newer Strains of COVID-19

2021

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At present, global vaccination for the SARS-CoV2 virus 2019 (COVID-19) is 95% effective. Generally, viral infections are arduous to cure due to the mutating nature of viral genomes, with the consequent quick development of resistance, posing significant fatalities or hazards. The novel corona viral strains are increasingly lethal than earlier variants, as those evolve faster than imagined. Despite the emergence of several present innovative treatment options, the vaccines, and available drugs, the latter still are the needs of the time. Therefore, repurposing the approved pharmaceutical drugs of a well-known safety profile would be ascertained to provide faster antiviral approaches for the newer strains of COVID-19. Recently, a combination of remdesivir, which has a competitively inhibitory effect on the nucleotide uptake in the virus, and the merimepodibs, an inhibitor of the enzyme inosine monophosphate dehydrogenase, which has a role in the synthesis of nucleotides of guanine bases, is in use in phase 2 clinical trials. However, new investigations suggest that using remdesivir, there is no statistically significant difference with uncertain clinical importance for moderate COVID-19 patients. Herein, an intellectual selection of approved drugs based on the safety profile is described, to target any essential enzymes that are required for the virus-receptor contact, fusion, and/or different stages of the life cycle of this virus, should help to screen drugs against newer strains of COVID-19. Graphical abstract

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Differing activities of oxysterol-binding protein (OSBP) targeting anti-viral compounds

Cited by 36 publications

References 37 publications

Antiviral Activity Exerted by Natural Products against Human Viruses

Antiviral Activity Exerted by Natural Products against Human Viruses

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

Targeting Some Enzymes with Repurposing Approved Pharmaceutical Drugs for Expeditious Antiviral Approaches Against Newer Strains of COVID-19

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