Table 3.
The overview of terpenoid compounds with anti-HSV activity.
| Compound | Antiherpetic and Cytotoxicity Assays, Strains, Cells, and Reference Agents | Results | Additional Information | Source | |
|---|---|---|---|---|---|
| Monoterpenes | Geraniol (62) | Vero cells, HSV-2 ACV (EC50 1.94 µg/mL; SI = 108.25 |
HSV-2 EC50 1.92 µg/mL SI = 109.38 |
Thymus bovei Benth. essential oil, typical monoterpene of Lamiaceae | [57] |
| Cypellocarpin C (63) | Vero cells, HSV-1 (KOS), HSV-2 (clinical isolates) PRA, TRI ACV HSV-1 IC50 1.92 ± 0.23 μg/mL, SI >109.4, HSV-2 IC50 1.75 ± 0.33, SI > 120.0 |
HSV-1 IC50 0.96 ± 0.12, SI > 218.8 | 63 is a cross-metabolite of monoterpenic glycoside and a methylchromone), Eucalyptus globulus | [58] | |
| (+)-rhodonoid C (64) | Vero cells, HSV-1 CPE ACV IC50 4.2 μM, SI > 100 |
IC50 80.6 ± 4.7 μM, SI = 2.7 |
64 is a cross-metabolite of monoterpene and polyketide Rhododendron spp. |
[59] | |
| Sesquiterpenes | β-caryophyllene (65) | Vero cells, HSV-1, HSV-2 (clinical isolates), (HSV-2 ACV-resistant) PRA Time-of-addition assay Virus inactivation assay ACV HS2-2 0.14 μg/mL; SI = 1178; HSV-2 (acyclovir-resistant) EC50 71.84 μg/mL, SI = 2.29 |
HSV-2 EC50 5.38 μg/mL, SI = 9.10 HSV-2 (acyclovir resistant) EC50 5.02 μg/mL, SI = 9.76 |
Bicyclic sesquiterpene, common occurrence, for example, cloves | [60] |
| Kellerin (66) | Vero cells, HSV-1 (KOS) PRA ACV at 2.5 µg/mL, 82% of plaque reduction |
66 at 2.5 µg/mL, 65% |
66 is a cross-metabolite of sesquiterpene and coumarin Gum resin of Ferula assa foetida No cytotoxic effect up to 10 µg/mL |
[61] | |
| Lactarorufin A 8-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate] (67) | Vero cells, HSV-1 (MacIntyre strain) CPE ACV IC50 1 µg/mL, SI ˃ 250 |
HSV-1 IC50 17.3 µg/mL, SI = 16 | Taxol-N-benzoylphenyl-isoserinates of sesquiterpenoid alcohols and sesquiterpenoids Lactarius mushroom |
[62] | |
| Isolactarorufin 8-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate] (68) | HSV-1 IC50 21.9 µg/mL, SI = 17.4 | ||||
| Furandiol 8-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate] (69) | HSV-1 IC50 15 µg/mL, SI = 19.3 | ||||
| Isovellerol 13-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate] (70) | HSV-1 IC50 7.8 µg/mL, SI = 13.9 | ||||
| 5-deoxylactarolid B 8-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate] (71) | HSV-1 IC50 3.4 µg/mL, SI = 31.7 | ||||
| Isolactarorufin 8-epi-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate] (72) | HSV-1 IC50 4.2 µg/mL, SI = 18.4 | ||||
| Alantolactone (73) | Vero cells, HSV-1 CPE Ribavirin as a positive control |
At 10-6–10-8 g/mL showed an antiviral effect | Sesquiterpene Inula helenium |
[63] | |
| (-)-15-methoxy-3,6-peroxocupar-1-ene (74) | Vero cells, HSV-1 (KOS strain, VR-1493) PRA ACV at 2.5 μM 96.96% |
Anti HSV-1at 10 μg/mL 43.93 % | Sesquiterpene Schisandra sphenanthera |
[64] | |
| (R)-6,9-dihydroxy-1-oxo-14-noreudesm-5,7,9-triene (75) | Vero cells, HSV-2 CPE inhibition method Quantitative PCR |
2 log10 reduction in HSV-2 yield at conc. 12.5 µM, IC50 6.25 μM |
14-Noreudesmane sesquiterpene Elaeagnus rhamnoides |
[65] | |
| Diterpenes | Simirane A (76) | Vero cells, HSV-1, HSV-2 PRA ACV HSV-1 EC50 0.8 μg/mL |
HSV-1 EC50 4.61 μg/mL, SI = 7.01 HSV-2 EC50 3.73 μg/mL, SI = 8.7 |
Erythroxylane diterpene, Simira eliezeriana | [51] |
| Dodovisnoid D (77) | Vero cells, HSV-1 CPE ACV IC50 4.2 μM, SI > 100 |
IC50 5.5 μM, SI = 2.8 |
Clerodane diterpenes Dodonaea viscosa |
[66] | |
| Dodovisnoid F (78) | IC50 23.0 μM, SI = 4.7 |
||||
| Atomaric acid (79) | Vero cells, HSV-1 (ACR-29) CPE ACV EC50 1.2 μM, SI > 716.6 |
EC50 1.28 µM, SI > 353.1 | Meroditerpenes from Brazilian seaweed Stypopodium zonale (Dictyotales) Atomaric acid (79) and epitanodiol (80) may be selectively targeted to HSV-1 replication Low effect on HIV-1 reverse transcriptase |
[67] | |
| Epitaondiol (80) | EC50 1.34 µM, SI > 361.9 | ||||
| 10-deacetyl-baccatin III (81) | Vero cells, HSV-1 (MacIntyre strain) CPE ACV IC50 1 µg/mL, SI ˃ 250 |
HSV-1 IC50 52.7 µg/mL, SI ˃ 9.5 | The activity may be associated with their influence on mitotic division. 113 and 114 are included for comparison of effect (non-terpenoid compounds) |
[68] | |
| Andrographolide (82) | Vero cells, HSV-1 PRA ACV IC50 < 1 µg/mL |
IC50 8.28 µg/mL | Ent-labdane diterpenes Andrographis paniculata No cytotoxic effect at virucidal concentration. |
[69] | |
| Neoandrographolide (83) | IC50 7.97 µg/mL | ||||
| 14-deoxy-11,12-didehydroandrographolide (84) | IC50 11.1 µg/mL | ||||
| 10,18-diacetoxy-8-hydroxy-2, 6-dolabelladiene (85) | Vero cells, HSV-1 CPE ACV at 15 µM, 79% of CPE |
At 50 µM, 89% of CPE | Dollabene diterpenes brown alga Dictyota pfaffi Effect on HIV-1 reverse transcriptase. |
[70] | |
| 10-acetoxy-8,18-di-hydroxy-2,6-dolabelladiene (86) | At 50 µM, 87% of CPE | ||||
| Steroids | Fomitopsin D (87) | Vero cells, HSV-1 Green fluorescent protein (GFP) expression ACV IC50 2.18 μg/mL |
HSV-1 IC50 17 μg/mL | Steroid Fungus Fomitopsis |
[71] |
| Lyonifoloside A (88) | Vero cells, HSV-1 (F strain VR 733) CPE ACV EC50 0.41 μM, SI > 244 |
EC50 11.1 μM, SI = 2.1 | 9,10-seco-cycloartanes 88–90, lanosterol derivatives 91–93 Lyonia ovalifolia |
[72] | |
| Lyonifolic acid A (89) | EC50 3.7 μM, SI = 4.3 | ||||
| Lyofoligenic acid (90) | EC50 11.1 μM, SI = 5.2 | ||||
| Lyonifolic acid C (91) | EC50 2.1 μM, SI = 7.6 | ||||
| Lyonifoloside M (92) | EC50 6.4 μM, SI = 3.0 | ||||
| Lyonifoloside P (93) | EC50 14.3 μM, SI > 7.0 | ||||
| Cucurbitacin B (94) | Vero cells, HSV-1 (KOS) PRA Acyclovir IC50 1.74 μM, SI > 132.2 |
IC50 0.94 μM, SI = 127.7 | Cucurbitane steroid Cucurbitaceae |
[73] | |
| TSH (halistanol (95) rich fraction) | Vero cells, HSV-1 (KOS) PRA Effects on HSV-1 attachment and penetration ACV IC50 3.45 ± 0.42 μg/mL, SI > 580 |
IC50 2.87 ± 0.78 μg/mL, SI = 15.53 | Brazilian marine sponge Petromica citrina (Demospongiae) The observed anti-HSV-1 activity was found to be mediated by the inhibition of virus attachment and by the penetration into Vero cells, the virucidal effect on virus particles, and by the impairment in levels of ICP27 and gD proteins of HSV-1. Synergic effect with acyclovir |
[74] | |
| Halistanol sulfate (96) | IC50 5.63 ± 1.37 μg/mL, SI = 2.46 | ||||
| Halistanol sulfate C (97) | IC50 6.09 ± 1.51 μg/mL, SI = 1.95 | ||||
| Pentacyclic triterpenes | Glycyrrhizic acid (98) | HeLa cells, HSV-1 CPE |
At 1 and 2 mM, the inhibition ranged from about 78% to 85% | Oleanane triterpene Glycyrrhizha spp. 24h pre-treatment strongly enhanced the antiviral activity of 98 (at 2 mM), with a viral inhibition that rise as high as 95%–98%. 98 is a strong inducer of the autophagy activator Beclin 1 (connected to resistance to HSV-1 infection). |
[75] |
| Glycyrrhetic acid (101) and its methylester (102) | Vero cells, HSV-1 strain (KOS) PRA ACV IC50 1.1 ± 0.09 µM, SI> 400 |
IC50 21.7 ± 0.06 and 8.1 ± 0.2 µM, respectively. SI = 3.9 and > 26, respectively. |
Oleanane triterpene Glycyrrhiza spp. The hydroxylation at C-21 seems to be responsible for the reduction of anti-HSV-1 activity, the C-29 hydroxy group would eliminate the anti-HSV-1 activity. C-20 methoxy or carboxy groups should be responsible for the enhancement of activity. |
[76] | |
| 3α-hydroxylup-20(29)-ene-23,28-dioic acid (99) | Vero cells, HSV-1 (15577) CPE ACV IC50 0.25 µg/mL, SI > 2000 |
IC50 31.3 µg/mL, SI = 3.8 | Lupane triterpenes Schefflera heptaphylla Other viruses tested |
[77] | |
| 3-epi-betulinic acid 3-O-sulphate (100) | IC50 20 µg/mL, SI = 5 | ||||
| Oleanolic acid (103) | Vero cells, HSV-1 (strain F), HSV-2 (strain G) CPE Viral inactivation or virucidal assay Viral penetration assay Time response assay Amplification of viral DNA by PCR ACV HSV-1 EC50 2.1 ± 0.1 μg/mL, SI = 61.9; HSV-2 EC50 2.9 ± 0.1 μg/mL, SI = 44.8 |
HSV-1 EC50 6.8 ± 1.24 μg/mL, SI = 14.4 HSV-2 EC50 7.8 ± 1.4 μg/mL, SI = 12.6 |
Common oleanane triterpene Possible inhibition of the early stage of HSV multiplication |
[78] | |
| Asprellanoside A (104) | Vero cells, HSV-1 PRA ACV total inhibitory concentration (TIC) 0.0043 mM |
TIC 0.14 mM | Sulphur containing triterpenoid saponins Ilex asprella |
[79] | |
| Oblonganoside H (105) | TIC 0.18 mM | ||||
| Tereticornate (106) | Vero cells, HSV-1 (KOS), HSV-2 (clinical isolates) PRA, TRI ACV HSV-1 IC50 1.92 ± 0.23 μg/mL, SI >109.4, HSV-2 IC50 1.75 ± 0.33, SI > 120.0 |
HSV-1 IC50 0.96 ± 0.12, SI > 218.8 |
106 - triterpene Eucalyptus globulus |
[58] | |
| 3β-O-trans-ferulyl-20-hydroxy-lup-28-oic acid (107) | Vero cells, HSV-1 (F strain VR 733) CPE inhibition method ACV IC50 0.41 ± 0.3 µM, SI > 243.9 |
IC50 0.71 ± 0.06, SI 5.2 | Triterpene Rhododendron latoucheae |
[80] | |