Effect of full-length and truncated variants of LL-37 on dengue virus infection and immunomodulatory effects of LL-37 in dengue virus infected U937-DC-SIGN cells

Jadhav, Nandadeep J.; Patil, Poonam; Alagarasu, Kalichamy

doi:10.1007/s10989-019-09861-z

Cited by 6 publications

(10 citation statements)

References 22 publications

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“…However, Western blot analysis revealed that sequence truncation suppressed the inhibitory effect of LL37 ( Figure S3B ), which suggests that LL37 blocks S1 adherence in a manner dependent on the primary structure, consistent with its structure-dependent antiviral action against dengue virus. 24 …”

Section: Resultsmentioning

confidence: 99%

Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone

Wang

et al. 2021

ACS Infect. Dis.

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SARS-CoV-2 infection begins with the association of its spike 1 (S1) protein with host angiotensin-converting enzyme-2 (ACE2). Targeting the interaction between S1 and ACE2 is a practical strategy against SARS-CoV-2 infection. Herein, we show encouraging results indicating that human cathelicidin LL37 can simultaneously block viral S1 and cloak ACE2. LL37 binds to the receptor-binding domain (RBD) of S1 with high affinity (11.2 nM) and decreases subsequent recruitment of ACE2. Owing to the RBD blockade, LL37 inhibits SARS-CoV-2 S pseudovirion infection, with a half-maximal inhibitory concentration of 4.74 μg/mL. Interestingly, LL37 also binds to ACE2 with an affinity of 25.5 nM and cloaks the ligand-binding domain (LBD), thereby decreasing S1 adherence and protecting cells against pseudovirion infection in vitro . Intranasal administration of LL37 to C57 mice infected with adenovirus expressing human ACE2 either before or after pseudovirion invasion decreased lung infection. The study identified a versatile antimicrobial peptide in humans as an inhibitor of SARS-CoV-2 attachment using dual mechanisms, thus providing a potential candidate for coronavirus disease 2019 (COVID-19) prevention and treatment.

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Section: Resultsmentioning

confidence: 99%

Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone

Wang

et al. 2021

ACS Infect. Dis.

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“…Molecular docking studies of DENV-2 E protein have revealed the direct binding of LL-37 with E2 protein moieties, further demonstrating the peptide’s ability to act as an entry inhibitor [43]. A more recent study assessed truncated and full length variants of LL-37 against other serotypes of DENV which revealed the inhibitory properties of LL-37 required the full length peptide [55]. In comparison to DENV-2, DENV-4 required higher concentrations of LL-37 for inhibition with effect being not as potent as with the former.…”

Section: Cathelicidin Ll-37mentioning

confidence: 99%

“…In comparison to DENV-2, DENV-4 required higher concentrations of LL-37 for inhibition with effect being not as potent as with the former. DENV-1 and DENV-3 inhibition however, was prominent at lower concentrations of LL-37 [55]. A recent study using DENV-2 infected keratinocytes has demonstrated the production of AMPs by infected cells as well as bystander cells [56].…”

Section: Cathelicidin Ll-37mentioning

confidence: 99%

“…Previously, α-MSH inhibited pro-inflammatory cytokine production such as TNFα and IL-1β in blood from HIV-infected individuals [145]. Barcellini et al [55] aimed to determine if α-MSH exhibits anti-HIV properties by utilizing chronically infected monocytic U1 cells and acutely infected monocyte-derived macrophages. Not only did U1 cells consistently produce α-MSH, but α-MSH and the tripeptide (KPV) both (10 µM) inhibited HIV expression at low concentrations comparable to physiological concentrations of α-MSH, with inhibition more pronounced at higher concentrations [146].…”

Section: Antimicrobial Neuropeptidesmentioning

confidence: 99%

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Human Antimicrobial Peptides as Therapeutics for Viral Infections

Ahmed

Siman-Tov

Hall

et al. 2019

Viruses

172

181

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Successful in vivo infection following pathogen entry requires the evasion and subversion of multiple immunological barriers. Antimicrobial peptides (AMPs) are one of the first immune pathways upregulated during infection by multiple pathogens, in multiple organs in vivo. In humans, there are many classes of AMPs exhibiting broad antimicrobial activities, with defensins and the human cathelicidin LL-37 being the best studied examples. Whereas historically the efficacy and therapeutic potential of AMPs against bacterial infection has been the primary focus of research, recent studies have begun to elucidate the antiviral properties of AMPs as well as their role in regulation of inflammation and chemoattraction. AMPs as therapeutic tools seem especially promising against emerging infectious viral pathogens for which no approved vaccines or treatments are currently available, such as dengue virus (DENV) and Zika virus (ZIKV). In this review, we summarize recent studies elucidating the efficacy and diverse mechanisms of action of various classes of AMPs against multiple viral pathogens, as well as the potential use of human AMPs in novel antiviral therapeutic strategies.

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“…LL37 is reported to have attenuated the replication of a number of viruses including several classified as Class IV single stranded (SS) enveloped RNA viruses similar to the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) that causes COVID-19 illness. LL37 has demonstrated anti-viral activity against diverse viruses include Respiratory Syncytial Virus (RSV) ( 24 , 26 ) Influenza A ( 27 ), hepatitis C (HCV) ( 28 ), Dengue virus (DENV) ( 29 ), HIV-1 ( 30 ) Vaccinia Virus ( 31 ), and others.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37

Crane-Godreau

Clem

Payne

et al. 2020

Front. Public Health

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Vitamin D deficiency and insufficiency (VDD) are widely recognized as risk factors for respiratory tract infections. Vitamin D influences expression of many genes with well-established relevance to airway infections and relevant to immune system function. Recently, VDD has been shown to be a risk factor for acquisition and severity of COVID-19. Thus, treating VDD presents a safe and inexpensive opportunity for modulating the severity of the disease. VDD is common in those over 60 years of age, many with co-morbid conditions and in people with skin pigmentation sufficient to reduce synthesis of vitamin D. Exposure to fine particulate air pollution is also associated with worse outcomes from COVID19. Vitamin D stimulates transcription of cathelicidin which is cleaved to generate LL37. LL37 is an innate antimicrobial with demonstrated activity against a wide range of microbes including envelope viruses. LL37 also modulates cytokine signaling at the site of infections. Fine particles in air pollution can interfere with LL37 destruction of viruses and may reduce effective immune signaling modulation by LL37. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Conclusion: Vitamin D plays an important role reducing the impact of viral lung disease processes. VDD is an acknowledged public health threat that warrants population-wide action to reduce COVID-19 morbidity and mortality. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Action is needed to address COVID-19 associated risks of air pollution from industry, transportation, domestic sources and from primary and second hand tobacco smoke.

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Effect of full-length and truncated variants of LL-37 on dengue virus infection and immunomodulatory effects of LL-37 in dengue virus infected U937-DC-SIGN cells

Cited by 6 publications

References 22 publications

Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone

Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone

Human Antimicrobial Peptides as Therapeutics for Viral Infections

Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37

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