pe
pep-05410 v1 CC-BY-SA-4.0

Esculentin antiviral peptide

A short protein fragment studied for fighting viruses; experimental and not an approved drug.

statusbioassayed targetANTIMICROBIAL length46 aa refs1
antiviral
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 2 / 5 · 0 verified on platform
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.570
avg pLDDT77.3
ranking score0.732
STRUCTURE · PEP-05410 × ANTIMICROBIAL
ranking0.732
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RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence46 aa
15101520253035404546
GLFSKLNKKKIKSGLI KIIKTAGKEAGLEALR TGIDVIGCKIKGEC
in the news 6 articles
Hypotheses5 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-05

Could the two ends of this peptide each do a different job, one fighting viruses and one fighting bacteria?

If true, scientists could cut the peptide in half and build a shorter, cheaper drug that does only what they need. It would also hint that the virus-fighting tip could be grafted onto other drug molecules as a reusable building block.

The hypothesis
The C-terminal CKIKGEC motif of pep-05410 forms a disulfide-constrained cyclic ring that is required for antiviral activity, whereas the N-terminal amphipathic helix (GLFSKLNKKKIKSGLIKIIK) drives membrane association and is primarily responsible for any antibacterial activity.
Why it’s plausible
The sequence ends in CKIKGEC: the two cysteines at positions 39 and 46 are separated by 6 residues, a spacing that in esculentin-1 family peptides universally forms a short C-terminal loop via a disulfide bond. Esculentin-1 and esculentin-2 peptides are known to differ in whether they carry this cyclic tail, and the cyclic tail has been implicated in selective interactions with structured viral or bacterial surface components versus the more promiscuous N-terminal helix. The N-terminal segment GLFSK...KIIK is highly helical and amphipathic on secondary structure prediction grounds, compatible with membrane insertion.
Why it matters
Pinpointing which module carries antiviral versus antimicrobial activity would allow truncated or cyclization-locked variants to be designed that maximize therapeutic index, and would confirm whether the C-terminal ring is a transferable antiviral pharmacophore applicable to other scaffolds.
Plausibility.78
Novelty.45
Impact.67
Basis · grounding1 paper · 1 computed/note
[1]
sequenceCKIKGEC at C-terminus with two cysteines separated by 6 residues matches the disulfide loop signature of esculentin-1 class peptides
[2]
paper
Source paper isolates esculentin-1 variants from Lithobates skin; esculentin-1 subclass is defined by the C-terminal disulfide ring
doi: 10.1016/j.peptides.2009.07.011
openupdated 2026-06-05

Does this peptide work by blocking the sticky surface that viruses use to grab onto your cells?

If this holds, the peptide could potentially work against a wide range of enveloped viruses, including herpes, SARS-CoV-2, dengue, and RSV, because all of them use the same docking mechanism. It would also mean the peptide is less likely to harm human cells, since it targets a viral attachment step rather than punching holes in membranes indiscriminately.

The hypothesis
Pep-05410 inhibits enveloped virus entry primarily by disrupting heparan sulfate proteoglycan-mediated viral attachment rather than by direct membrane lysis, owing to its exceptionally high cationic charge density (at least 9 lysine residues across 46 amino acids).
Why it’s plausible
The sequence GLFSKLNKKKIKSGLIKIIKTAGKEAGLEALRTGIDVIGCKIKGEC contains a striking cluster of lysines (positions 5, 9, 10, 12, 17, 18, 21, 25, 38, 41), giving the peptide a net charge that would compete electrostatically with heparan sulfate proteoglycans for cationic binding sites on virion surfaces. Axis hits note that HS affinity appears central to predictive models of antiviral peptide selectivity. The classic esculentin-1 antimicrobial mechanism involves membrane disruption, but a purely membrane-lytic mechanism would not explain selective antiviral tagging without corresponding broad cytotoxicity data. Competitive HS blockade is an alternative that reconciles high cationicity with antiviral selectivity.
Why it matters
If pep-05410 targets the HS docking step, it would be active against a broad spectrum of HS-dependent enveloped viruses (herpes simplex, SARS-CoV-2, dengue, RSV) and its mechanism would be fundamentally different from the membrane-disruption attributed to other esculentin family members, reframing its development path.
Plausibility.57
Novelty.43
Impact.68
Basis · grounding2 papers · 1 computed/note
[1]
sequenceAt least 9 lysine residues in 46 aa give exceptionally high cationic charge density suited for electrostatically blocking sulfated proteoglycans
[2]
paper
HS affinity identified as key determinant of antiviral peptide selectivity in predictive models
doi: 10.1111/j.1747-0285.2006.00412.x
[3]
paper
Peptide isolated from Lithobates skin as esculentin family member annotated for antimicrobial and antiviral activity
doi: 10.1016/j.peptides.2009.07.011
openupdated 2026-06-05

Could a single chemical change stop the blood from dismantling this peptide before it reaches its target?

Blood contains molecules that quickly break the chemical bond holding part of this peptide in shape. If swapping that bond for a tougher version extends its lifetime in the body by several times, it could turn a promising lab result into something worth testing in animals, accelerating the whole development timeline.

The hypothesis
Constraining the disulfide bond in pep-05410's CKIKGEC loop by replacing it with a lactam bridge or a thioether staple will extend plasma half-life by more than 5-fold compared to the native peptide without reducing antiviral potency, because the native disulfide is susceptible to reduction in the blood compartment.
Why it’s plausible
The axis hit on proteolytic stability notes that D-amino acid substitution and other engineering strategies are needed to stabilize AMPs in serum. For esculentin-class peptides, the C-terminal disulfide is functionally important but chemically vulnerable: physiological glutathione and thioredoxin concentrations will rapidly reduce it in plasma (GSH approximately 1-10 mM intracellularly, and even extracellular plasma contains approximately 1-5 microM). Loss of ring constraint upon reduction would alter the peptide conformation and likely diminish any structure-dependent antiviral activity. A thioether staple (diaminobutyric acid crosslink) or lactam constrained analog would preserve ring geometry while being redox-stable.
Why it matters
The manufacturing axis hit notes that 46 aa is near the solid-phase synthesis length limit and that stability is a fundamental challenge; if a single chemical substitution in the ring converts a plasma-labile peptide to a stable one, it dramatically accelerates the path to in vivo efficacy testing.
Plausibility.53
Novelty.47
Impact.57
Basis · grounding2 papers · 1 computed/note
[1]
sequenceCKIKGEC at positions 39-46 contains two cysteines forming a disulfide ring that would be susceptible to reduction by physiological thiols
[2]
paper
D-amino acid substitution and structural modifications improve peptide stability in serum and resist enzymatic degradation; the design rationale extends to disulfide-vulnerable cyclic elements
doi: 10.1248/cpb.c25-00478
[3]
paper
Engineered fusion inhibitor peptides improved pharmacokinetics up to 100-fold relative to native sequence, demonstrating that chemical engineering of peptide structure can yield large stability gains
doi: 10.1073/pnas.0701478104
openupdated 2026-06-05

Could a peptide cataloged only for fighting viruses also work against fungal infections that resist most current drugs?

Candida biofilms, the sticky protective coatings fungi build inside the body, are notoriously hard to treat and cause serious illness in hospital patients. If this peptide disrupts those biofilms at safe doses, it could be repurposed using material already on hand, with no new synthesis needed.

The hypothesis
Pep-05410 disrupts biofilm formation by Candida albicans at subinhibitory concentrations through its cationic amphipathic structure, making it active against fungal infections despite being cataloged solely as antiviral, because the biophysical properties that disrupt viral membranes overlap with those that penetrate fungal cell walls.
Why it’s plausible
Esculentin family peptides from frog skin are well established as broad-spectrum antimicrobials (the source paper describes antimicrobial peptide families). The specific annotation of pep-05410 as antiviral with no antibacterial or antifungal tag may reflect the assay conditions reported in the primary reference rather than a genuine mechanistic restriction. Candida biofilm is a charged extracellular matrix that cationic AMPs can penetrate; frog-skin esculentins have documented antifungal activity. A 46 aa amphipathic cationic peptide from this family is a strong prior candidate for antifungal biofilm disruption.
Why it matters
Candida biofilm infections are refractory to most clinical antifungals; if pep-05410 disperses biofilm at non-toxic concentrations it represents a repurposing opportunity requiring only repositioning of existing experimental material, with no new synthesis needed.
Plausibility.58
Novelty.38
Impact.52
Basis · grounding1 paper · 1 computed/note
[1]
paper
Source paper characterizes peptides from Lithobates frog skin across multiple AMP families including esculentins, which are known broad-spectrum antimicrobials beyond the antiviral annotation
doi: 10.1016/j.peptides.2009.07.011
[2]
sequenceHigh cationic charge and amphipathic character are the two biophysical properties that drive fungal membrane disruption and biofilm matrix penetration in characterized antifungal esculentins
openupdated 2026-06-05

Could this peptide keep working against future COVID variants because it targets the human cell surface rather than the virus's ever-changing spike protein?

Vaccines and antibodies that target the spike protein lose effectiveness as the virus mutates. If this peptide works by blocking a stable docking site on human cells instead, it could retain potency across variants, filling a real gap that current antivirals struggle with.

The hypothesis
Pep-05410 retains antiviral potency against SARS-CoV-2 variants because its mechanism targets a host cell surface component (heparan sulfate or a conserved lipid membrane feature) rather than the rapidly mutating spike protein receptor binding domain.
Why it’s plausible
Axis hits focus on the challenge of resistance emergence and the desirability of mechanisms that do not select for resistance easily (axis hit citing C5A virocidal peptide against HCV). Pep-05410 has no annotated viral target, meaning its mechanism is uncharacterized and could be host-directed. SARS-CoV-2 is known to depend on heparan sulfate for initial attachment. A peptide with 9+ cationic residues would compete for HS binding regardless of spike sequence variation, potentially maintaining efficacy across variants in a way that receptor-blocking antibodies cannot.
Why it matters
Variant-resistant antivirals operating through host-directed mechanisms are a major unmet need; demonstrating that pep-05410 retains activity across spike-diverse variants would establish it as a broad-spectrum respiratory antiviral lead.
Plausibility.45
Novelty.32
Impact.72
Basis · grounding2 papers · 1 computed/note
[1]
paper
C5A virocidal peptide inhibits both initiation and ongoing HCV infection and does not select resistant mutations, validating host-component or conserved viral surface targeting as a resistance-avoidant strategy
doi: 10.1128/jvi.02201-12
[2]
paper
HS affinity is central to antiviral peptide activity prediction; HS is a conserved host attachment factor for many enveloped viruses
doi: 10.1111/j.1747-0285.2006.00412.x
[3]
sequenceHigh net positive charge from 9+ lysines suitable for HS competitive inhibition that is independent of viral protein sequence variation
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.7322196364402771 boltz-2
3-letter notation
Gly-Leu-Phe-Ser-Lys-Leu-Asn-Lys-Lys-Lys-Ile-Lys-Ser-Gly-Leu-Ile-Lys-Ile-Ile-Lys-Thr-Ala-Gly-Lys-Glu-Ala-Gly-Leu-Glu-Ala-Leu-Arg-Thr-Gly-Ile-Asp-Val-Ile-Gly-Cys-Lys-Ile-Lys-Gly-Glu-Cys
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategynone_monomer
runtime
predicted by
predicted at2026-05-23
citationbibtex
peptidemodel (2026). Esculentin antiviral peptide (pep-05410, v1). PeptideModel. https://peptidemodel.com/card/pep-05410
@peptide{pep05410,
  sequence = {GLFSKLNKKKIKSGLIKIIKTAGKEAGLEALRTGIDVIGCKIKGEC},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
references 1 papers
[1]
Antimicrobial peptides from the skin secretions of the New World frogs Lithobates capito and Lithobates warszewitschii (Ranidae)
Conlon J; Meetani M; Coquet L; Jouenne T; Leprince J; Vaudry H; Kolodziejek J; Nowotny N; King J Peptides 2009
source scaffold
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