Table 1. Natural peptides and their analogues inhibit HIV.
| Native Peptide |
Origin or Analogue |
Sequence | IC50 μM |
CC50 μM |
Therapeutic Index |
Mechanism of HIV Inhibition |
Ref. | |
|---|---|---|---|---|---|---|---|---|
| α-helix | cecropin A | Hyalophora cecropia | KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAL-NH2 | 2.0-3.0 | 2.0-4.0 | 1.2 | [69] | |
| mellitin | Apis mellifera | GIGAVLKVLTTGLPALISWIKRKRQQ-NH2 | 0.90 | 0.94 | 1.0 | Suppress viral gene expression | [69] | |
| LL-37 | Homo sapiens | LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES | 20 | >45 | >2.3 | Inhibit Reverse Transcriptase and Protease | [70, 71], A | |
| LL37 | LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES | 15 | >130 | >8.3 | B | |||
| LL13-37 | IGKEFKRIVQRIKDFLRNLVPRTES | 7.0 | >130 | >18 | B | |||
| LL17-32 | FKRIVQRIKDFLRNLV | 70 | >130 | >1.8 | B | |||
| LL-37 | LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES | 1.6 | 18 | 12 | [72] | |||
| GI-20 | GIKEFKRIVQRIKDFLRNLV | 1.1 | 23 | 21 | [72] | |||
| GI-20Q16 | GIKQFKRIVQRIKDFLRNLV | 0.91 | 14 | 15 | [72] | |||
| dermaseptin S4 | ALWMTLLKKVLKAAAKAALNAVLVGANA | 2.0 | 4.5 | 2.3 | Disrupts Virion Integrity, Attachment, Transcytosis, Dendritic-to-T-Cell transfer | [73], C, D | ||
| dermaseptin S4a | ALWMTLLKKVLKAAAKAALNAVLVGANA-NH2 | 2.0 | 5.6 | 2.8 | C | |||
| dermaseptin K4-S4a | ALWKTLLKKVLKAAAKAALNAVLVGANA-NH2 | 1.4 | 17 | 12 | C | |||
| dermaseptin S4(1-16)a | ALWMTLLKKVLKAAAK-NH2 | >19 | 19 | <1 | C | |||
| dermaseptin K4-S4-(1-16)a | ALWKTLLKKVLKAAAK-NH2 | 28 | >100 | >3.6 | C | |||
| maximin 3 | Bombina maxima | GIGGKILSGLKTALKGAAKELASTYLH | 0.56 | 4.2 | 7.6 | [74] | ||
| lysozyme | Homo sapiens | 148 aa. 14.7kDA | 0.064 | E | ||||
| HL18 | RVVRDPQGIRAWVAWRNR (98-115) | 0.062 | E | |||||
| HL9 | RAWVAWRNR (107-115) | 0.055 | E | |||||
| caerin 1.9 | Litoria chloris | GLFGVLGSIAKHVLPHVVPVIAEKL-NH2 | 1.2 | 20-25 | 19 | Virucidal | F | |
| caerin 1.1 | Litoria caerulea | GLLSVLGSVAKHVLPHVVPVIAEHL-NH2 | 7.8 | >30 | >3.8 | Virucidal | F, G | |
| maculatin 1.1 | Litoria genimaculata | GLFGVLAKVAAHVVPAIAEHF-NH2 | 11 | F, G | ||||
| ponericin L2 | Pachycondyla goeldii | LLKELWTKIKGAGKAVLGKIKGLL-NH2 | 1.4 | 25 | 18 | H, I | ||
| spinigerin | Pseudacanthot ermes spiniger | HVDKKVADKVLLLKQLRIMRLLTRL | 3.1 | >33 | >11 | I, [75] | ||
| β-sheet | gpnp | Cavia porcellus | RRCICTTRTCRFPYRRLGTCIFQNRVYTFCC | 7.9 | >130 | >16 | [76, 77] | |
| rbnp-1 | Oryctolagus cuniculus | VVCACRRALCLPRERRAGFCRIRGRIHPLCCRR | 9.7 | >130 | >13 | [76, 78-80] | ||
| ratnp-4 | Rattus norvegicus | VTCYCRRTRCGFRERLSGACGYRGRIYRLCCR | 7.4 | >130 | >18 | [76, 81] | ||
| hnp1 | Homo sapiens | ACYCRIPACIAGERRYGTCIYQGRLWAFCC | 5-20 | >8.7 | >.70 | Inhibit HIV gene exp., Upregulate CC-Chemokines, Inhibit fusion | [82, 83], J | |
| hnp2 | Homo sapiens | CYCRIPACIAGERRYGTCIYQGRLWAFCC | 5-20 | Upregulate CC-Chemokines, Inhibit Fusion | [83, 84], J | |||
| hnp3 | Homo sapiens | DCYCRIPACIAGERRYGTCIYQGRLWAFCC | 5-20 | J | ||||
| hnp4 | Homo sapiens | VCSCRLVFCRRTELRVGNCLIGGVSFTYCCTR | 2-5 | J | ||||
| hbd2 | Homo sapiens | GIGDPVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKCCKKP | 2.1-9.2 | >9.2 | >1.6 | Inactivate virions, downregulate CXCR4 | K | |
| hbd3 | Homo sapiens | GIINTLQKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCRRKK | 1.7-7.8 | >7.8 | >1.6 | [85], K | ||
| β-turn/hairpin | protegrin 1 | Sus scrofa | RGGRLCYCRRRFCVCVGR-NH2 (6-15, 8-13) | 0.46-10.9 | 4.6-81 | 7.5 | A, L, M, N | |
| PG-1(OH) Type I | RGGRLCYCRRRFCVCVGR-OH (6-8, 13-15) | 1.1 | 7.8 | 7.3 | M | |||
| PG-1(OH) Type II | RGGRLCYCRRRFCVCVGR-OH (6-13, 8-15) | 1.1 | 8.9 | 8.0 | M | |||
| PG-1(OH) Type III | RGGRLCYCRRRFCVCVGR-OH (6-15, 8-13) | 1.4 | 6.8 | 4.7 | M | |||
| 4-Cys(ACM)-PG-I-(OH) | RGGRLCYCRRRFCVCVGR-OH (LINEAR) | 1.6 | 180 | 120 | M | |||
| cPG2 | RGGRLCYCRRRFCVCVGR (CYCLIC) | 12.8 | 140 | 11 | N | |||
| ccPG3 | RGGCLCYCRRRFCVCVCR (CYCLIC, 3 bonds) | 12.2 | 800 | 65 | N | |||
| griffithsin | Griffithsia sp. | 121 aa. 12.7kDa | 3.6E-6-6.3E-6 | >0.78 | >2400 | Binds glycosylated gp120 | O | |
| grifonin-1 | Cha-SC-Chg-R-Chg-RSGSY-Cha-DN-Chg-R-Chg-c-NH2 | 0.19-0.55 | >20 | >54 | P | |||
| polyphemusin II | Limulus polyphemus | RRWCFRVCYKGFCYRKCR-NH2 | 0.42 | 11 | 25 | Binds CXCR4 | Q | |
| T22 | RRWCYRKCYKGYCYRKCR-NH2 | 0.080 | 13 | 170 | Q | |||
| T140 | RR-2Nal-CYRKk-PYR-Cit-CR | 0.0035 | 45 | 13000 | Q | |||
| tachyplesin I | Tachypleus tridentatus | KWCFRVCYRGICYRRCR-NH2 | >20 | 8.4 | <.42 | Binds CXCR4 | Q | |
| VIRIP | Homo sapiens | LEAIPMSIPPEVKFNKPFVF | 15 | >1000 | >68 | Binds Env - gp41 | R | |
| (-L)VIRIP | EAIPMSIPPEVKFNKPFVF | >1000 | >1000 | R | ||||
| VIR-175 | LEAIPMSIPPEFLFGKPFVF | 1.3 | >1000 | >750 | R | |||
| VIR-353 | LEAIPCSIPpCFLFNKPFVF | 0.20 | >1000 | >5000 | R | |||
| alpha-MSH | Homo sapiens | SYSMEHFRWGKPV | 10 | NF-kB Inhibitor | [86, 87], S | |||
| KPV | KPV | 10 | S | |||||
| cyclic | retrocyclin I | RCICGRGICRCICGRGIC | 3.7 | >52 | >14 | Fusion inhibitor -lectin | T, U | |
| RC-101 | RCICGRGICRCICGKGIC | 0.03-4.5 | >260 | >120 | T | |||
| retrocyclin II | RCICGRRICRCICGRGIC | 0.52-1.6 | >15 | >14 | [88] | |||
| rtd1 | Macaca mulatta | GFCRCLCRRGVCRCICTR | 0.45-1.9 | >48 | >41 | [88-91] | ||
| rtd2 | Macaca mulatta | GVCRCLCRRGVCRCICRR | 0.83-3.2 | [88, 90] | ||||
| rtd3 | Macaca mulatta | GFCRCICTRGFCRCICTR | 0.84-2.1 | [88, 90] | ||||
| circulin a | Chassalia parvifolia | NKVCYRNGIPCGESCVWIPCISAALGCSCK | 0.04-0.26 | 0.50 | 3.3 | V, [92] | ||
| circulin b | Chassalia parvifolia | NKVCYRNGVIPCGESCVFIPCISTLLGCSCK | 0.04-0.26 | 0.50 | 3.3 | V, [92] | ||
| kalata b1 | Oldenlandia affinis | WPVCTRNGLPVCGETCVGGTCNTPGCTCS | 0.66 | 12 | 18 | W, [92] | ||
| cycloviolacin Y1 | Viola yedoenis | GGTIFDCGETCFLGTCYTPGCSCGNYGFCYGTN | 1.2 | >40 | 33 | W | ||
| cycloviolacin Y4 | Viola yedoenis | GVPCGESCVFIPCITGVIGCSCSSNVCYLN | 0.12 | 9.3 | 78 | W | ||
| cycloviolacin Y5 | Viola yedoenis | GIPCAESCVWIPCTVTALVGCSCSDKVCYN | 0.04 | 8.7 | 220 | W | ||
| siamycin I | Streptomyces sp. | CLGVGSCNDFAGCGYAIVCFW | 0.05-5.7 | 93-150 | 42.2 | Fusion inhibitor | [93-95] | |
| Other | indolicidin | Bos taurus | LPWKWPWWPWRR-NH2 | 47 | 18.4 | 0.4 | Virucidal, Integrase Inhibition | X |
| gramicidin d | Bacillus brevis | VGAlAvVvWlWlWlW-ETA | 8.2E-6 | 8.2E-3 | 1000 | [96, 97], Y |
A comprehensive compilation of natural peptides that inhibit HIV is shown, along with their structural motif, source, derived analogues, and sequence. For larger proteins whose activity is attributed to a smaller peptide domain, the parent protein and its derivatives are assigned according to the active domain structure. Structural classification is nonexclusive, as some cyclic peptides (e.g. retrocyclins and RTDs) contain β-turn motifs, and β-turns can also be considered β-sheets. Some peptides (e.g. VIRIP) were classified based on structural evidence rather than absolute classification. D-isomer amino acids are shown in lowercase, and non-canonical residues are abbreviated as:
Cha = (L)-Cyclohexylalanine
Chg = (L)-Cyclohexylglycine
Cit = (L)-Citrulline
2Nal = 3-(2-naphthyl)alanine
ETA = ethanolamine
Notable peptide modifications are bolded. For protegrin analogues, bond arrangements are indicated in parentheses. When available, mechanism of inhibition, IC50 and CC50 and therapeutic index are also included. All numbers were rounded to 2 significant figures. For IC50 or CC50 concentrations that were reported as a range, the mid-range value was used for calculating the therapeutic index.
Reference Key: A - Ref [38], B - Ref [37], C - Ref [16], D - Ref [19], E - Ref [18], F - Ref [15], G - Ref 17, H - Ref [14], I - Ref. [40], J - Ref [24], K - Ref. [28], L - Ref. [56], M - Ref. [57], N - Ref. [58], O - Ref. [26], P - Ref. [22], Q - Ref. [45], R - Ref. [30], S - Ref. [43], T - Ref. [29], U - Ref. [23], V - Ref. [13], W - Ref [11], X - Ref. [39], Y - Ref. [12].