Human cathelicidin peptide LL-37 as a therapeutic antiviral targeting Venezuelan equine encephalitis virus infections

Ahmed, Aslaa; Siman-Tov, Gavriella; Keck, Forrest; Kortchak, Stephanie; Bakovic, Allison; Risner, Kenneth; Lu, Timothy K.; Bhalla, Nishank; Fuente-Núñez, César de la; Narayanan, Aarthi

doi:10.1016/j.antiviral.2019.02.002

Cited by 51 publications

(44 citation statements)

References 26 publications

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“…Furthermore, cathelicidin LL-37 [108] demonstrates inhibitory activity toward several enveloped viruses, including: VZV; the vaccinia virus (VV), HSV-1; HIV; the syncytial respiratory virus (RSV); influenza A virus; HCV; dengue virus serotype 2; Zika virus; and, more recently, Venezuelan equine encephalitis virus (VEEV), which can infect both equines and humans [35,45,[109][110][111][112][113][114]. The proposed mechanism of action against enveloped viruses is described as damaging the envelope or protecting the target cells against infection.…”

Section: Avps Derived From Mammalsmentioning

confidence: 99%

Antiviral peptides as promising therapeutic drugs

Boas

Campos

Berlanda

et al. 2019

Cell. Mol. Life Sci.

251

175

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While scientific advances have led to large-scale production and widespread distribution of vaccines and antiviral drugs, viruses still remain a major cause of human diseases today. The ever-increasing reports of viral resistance and the emergence and re-emergence of viral epidemics pressure the health and scientific community to constantly find novel molecules with antiviral potential. This search involves numerous different approaches, and the use of antimicrobial peptides has presented itself as an interesting alternative. Even though the number of antimicrobial peptides with antiviral activity is still low, they already show immense potential to become pharmaceutically available antiviral drugs. Such peptides can originate from natural sources, such as those isolated from mammals and from animal venoms, or from artificial sources, when bioinformatics tools are used. This review aims to shed some light on antimicrobial peptides with antiviral activities against human viruses and update the data about the already well-known peptides that are still undergoing studies, emphasizing the most promising ones that may become medicines for clinical use.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Avps Derived From Mammalsmentioning

confidence: 99%

Antiviral peptides as promising therapeutic drugs

Boas

Campos

Berlanda

et al. 2019

Cell. Mol. Life Sci.

251

175

View full text Add to dashboard Cite

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“…However, direct interaction with AMPs can also cause viral particles extracellular aggregation blocking virus entry and leading to an increase of virus uptake by phagocytes. Treatment with LL-37 caused clumping of Venezuelan equine encephalitis virus (VEEV), thereby preventing cell infection (Ahmed et al, 2019b;Lai et al, 2011). Finally, the pre-fusion antiviral activity of AMPs can be linked to an inhibition of virus attachment to its receptor at the cell surface.…”

Section: Direct Antiviral Effects Of Keratinocyte Ampsmentioning

confidence: 99%

“…The addition of LL-37 to HRVinfected human bronchial epithelial cells enhanced IL-6 and CCL-2 production (Lai et al, 2011). It also increased the expression of type I IFN during VEEV infection (Lai et al, 2011;Ahmed et al, 2019b). However, paradoxical pro-and anti-inflammatory properties of LL-37 were also observed in the context of viral infection (Tripathi et al, 2014).…”

Section: Modulation Of Inflammatory Response By Ampsmentioning

confidence: 99%

Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes

et al. 2020

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Keratinocytes, the main cells of the epidermis, are the first site of replication as well as the first line of defense against many viruses such as arboviruses, enteroviruses, herpes viruses, human papillomaviruses, or vaccinia virus. During viral replication, these cells can sense virus associated molecular patterns leading to the initiation of an innate immune response composed of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. Human keratinocytes produce and secrete at least nine antimicrobial peptides: human cathelicidin LL-37, types 1-4 human β-defensins, S100 peptides such as psoriasin (S100A7), calprotectin (S100A8/9) and koebnerisin (S100A15), and RNase 7. These peptides can exert direct antiviral effects on the viral particle or its replication cycle, and indirect antiviral activity, by modulating the host immune response. The purpose of this review is to summarize current knowledge of antiviral and immunomodulatory properties of human keratinocyte antimicrobial peptides.

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“…Also promising is the virus-specific antiviral ML336 that inhibits Nsp4 of VEEV and EEEV in vivo [72]. Less well-described compounds are LL-37 peptide, an alphavirus entry inhibitor in vitro [4], compound 25 that was identified in silico and optimized to inhibit CHIKV replication in vitro [9], Prest-37 and -392, with in vitro activity against VEEV nsP1 capping enzyme [41], and baicalin, which inhibits CHIKV replication in vitro by interfering with a cellular target [113].…”

Section: Alphaviridaementioning

confidence: 99%

Antivirals in medical biodefense

et al. 2020

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The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses and a number of arboviruses causing encephalitis, including alpha-and flaviviruses. All these viruses are of concern for public health services when they occur in natural outbreaks or emerge in unvaccinated populations. Recent events and intelligence reports point to a growing risk of dangerous biological agents being used for nefarious purposes. Public health responses effective in natural outbreaks of infectious disease may not be sufficient to deal with the severe consequences of a deliberate release of such agents. One important aspect of countermeasures against viral biothreat agents are the antiviral treatment options available for use in post-exposure prophylaxis. These issues were adressed by the organizers of the 16th Medical Biodefense Conference, held in Munich in 2018, in a special session on the development of drugs to treat infections with viruses currently perceived as a threat to societies or associated with a potential for misuse as biothreat agents. This review will outline the state-of-the-art methods in antivirals research discussed and provide an overview of antiviral compounds in the pipeline that are already approved for use or still under development.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Human cathelicidin peptide LL-37 as a therapeutic antiviral targeting Venezuelan equine encephalitis virus infections

Cited by 51 publications

References 26 publications

Antiviral peptides as promising therapeutic drugs

Antiviral peptides as promising therapeutic drugs

Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes

Antivirals in medical biodefense

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