Linear and dendrimeric antiviral peptides: design, chemical synthesis and activity against human respiratory syncytial virus

Kozhikhova, Ksenia V.; Shilovskiy, Igor; Shatilov, Artem; Timofeeva, Anastasiia V; Turetskiy, Evgeniy A.; Vishniakova, Liudmila I; Nikolskii, A.A.; Barvinskaya, Ekaterina D; Karthikeyan, S.; Смирнов, В. В.; Kudlаy, D.А.; Андреев, С. М.; Khaitov, Musa

doi:10.1039/c9tb02485a

Cited by 21 publications

(12 citation statements)

References 44 publications

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“…Similar to this study, in silico analyses showed the potent antiviral effects of AMPs against Betacoronavirus [27,39]. According to our results, the AMPs are attractive candidates as alternative to conventional antiviral drugs to control SARS-CoV-2 infection, because they offer several potential advantages, including specific anti-CoV effects, high selectivity, and do not be associated with severe adverse effects according to in vitro and in vivo assays [58][59][60].…”

Section: Moleculesupporting

confidence: 83%

In Silico Discovery of Antimicrobial Peptides as an Alternative to Control SARS-CoV-2

2020

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A serious pandemic has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The interaction between spike surface viral protein (Sgp) and the angiotensin-converting enzyme 2 (ACE2) cellular receptor is essential to understand the SARS-CoV-2 infectivity and pathogenicity. Currently, no drugs are available to treat the infection caused by this coronavirus and the use of antimicrobial peptides (AMPs) may be a promising alternative therapeutic strategy to control SARS-CoV-2. In this study, we investigated the in silico interaction of AMPs with viral structural proteins and host cell receptors. We screened the antimicrobial peptide database (APD3) and selected 15 peptides based on their physicochemical and antiviral properties. The interactions of AMPs with Sgp and ACE2 were performed by docking analysis. The results revealed that two amphibian AMPs, caerin 1.6 and caerin 1.10, had the highest affinity for Sgp proteins while interaction with the ACE2 receptor was reduced. The effective AMPs interacted particularly with Arg995 located in the S2 subunits of Sgp, which is key subunit that plays an essential role in viral fusion and entry into the host cell through ACE2. Given these computational findings, new potentially effective AMPs with antiviral properties for SARS-CoV-2 were identified, but they need experimental validation for their therapeutic effectiveness.

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Section: Moleculesupporting

confidence: 83%

In Silico Discovery of Antimicrobial Peptides as an Alternative to Control SARS-CoV-2

2020

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“…Αlthough AMPs seem especially promising therapeutic tools against viral pathogens, there are certain limitations in their clinical use mainly due to their pharmacokinetics, as they seem to have low metabolic stability and undergo degradation by proteolytic enzymes in the systemic circulation. Consequently, the use of novel techniques that improve AMPs properties, such as synthetic analogues formation, have generated increasing interest within the academic and pharmaceutical communities [34][35][36] . Currently, although AMPs can be administered by various routes, many researchers consider topical application the only effective way for safe clinical use.…”

Section: Discussionmentioning

confidence: 99%

LL-37 levels in nasal secretions are associated with the severity of acute bronchiolitis

Papadaki¹,

Marmarinos²,

Τσολιά³

et al. 2020

Preprint

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Objective: Τo investigate the association of serum vitamin D and nasal secretion antimicrobial peptides (AMPs) levels with the severity of acute bronchiolitis. Study design: We conducted a prospective single pediatric tertiary care center cohort study of inpatients aged 0-18 months with a first episode of acute bronchiolitis from November 1st 2014 to April 30th 2017. Disease severity was determined by the length of hospitalization and supplemental hospital data. Qualitative measurements included serum 25(OH)D and nasal secretion LL-37 and β-defensin-2 levels. Correlations were examined with the Mann-Whitney and Kruskal-Wallis criteria for qualitative and the correlation coefficient Spearman’s rho for quantitative factors. Multiple linear and logarithmic regression were performed in order to adjust for confounding factors. Results: The study population consisted of 153 infants and toddlers with mean age 3.6 months (SD: +2.8). The median level of serum 25(OH)D was 51.4 nmol/L (IQR: 29.7-72.2). No association was found between serum 25(OH)D and AMPs nasal secretions levels. Serum 25(OH)D and nasal secretion β-defensin-2 levels were not associated with the severity of bronchiolitis. In contrast, LL-37 levels were inversely associated with the length of hospitalization (rho = -0.340, p = 0.001) and the need for medication use (p = 0.001) and this association remained significant after adjustment for potential confounders. Conclusion: A significant association between LL-37 nasal secretions levels with the severity of acute bronchiolitis was found in hospitalized infants and toddlers. The role of LL-37 in the pathogenesis of bronchiolitis merits further investigation.

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“…acting as competitive inhibitors by interfering with binding [75]. The synthetic linear peptides SA-35 (Met-Ile-Thr-His-Gly-Cys-Tyr-Thr-Arg-Thr-Arg-His-Lys-His-Lys-Leu-Lys-Lys-Thr-Leu) and dendrimer LTP ((((Arg) 2 Lys) 2 Lys) 2 Lys-Ala-Cys) peptides have been shown to exhibit excellent antiviral activity against the respiratory syncytial virus, which causes a dangerous disease mainly affecting children [76]. The main characteristic of these two peptides is the evenly positive charge distribution with low amphipathic amino acid residues.…”

Section: Antiviral Peptidesmentioning

confidence: 99%

Nanoscale Pathogens Treated with Nanomaterial-Like Peptides: A Platform Technology Appropriate for Future Pandemics

Nahhas

Webster

2021

Nanomedicine (Lond.)

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Viral infections are historically very difficult to treat. Although imperfect and time-consuming to develop, we do have some conventional vaccine and therapeutic approaches to stop viral spreading. Most importantly, all of this takes significant time while viruses continue to wreak havoc on our healthcare system. Furthermore, viral infections are accompanied by a weakened immune system which is often overlooked in antiviral drug strategies and requires additional drug development. In this review, for the first time, we touch on some promising alternative approaches to treat viral infections, specifically those focused on the use of platform nanomaterials with antiviral peptides. In doing so, this review presents a timely discussion of how we need to change our old way of treating viruses into one that can quickly meet the demands of COVID-19, as well as future pandemic-causing viruses, which will come.

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Linear and dendrimeric antiviral peptides: design, chemical synthesis and activity against human respiratory syncytial virus

Abstract: Novel artificial peptides possess anti-RSV activity through a combination of two mechanisms: direct nonspecific destabilization of the viral envelope and competitive interaction with the RSV cellular receptor.

Cited by 21 publications

References 44 publications

In Silico Discovery of Antimicrobial Peptides as an Alternative to Control SARS-CoV-2

In Silico Discovery of Antimicrobial Peptides as an Alternative to Control SARS-CoV-2

LL-37 levels in nasal secretions are associated with the severity of acute bronchiolitis

Nanoscale Pathogens Treated with Nanomaterial-Like Peptides: A Platform Technology Appropriate for Future Pandemics

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