Table 7.
Bioactive natural products reported as inducing potent anti-HSV properties.
| Chemical Class | Compound | Mechanisms of Action or Types of Inhibition |
Structure–Activity Relationship (SAR) |
|---|---|---|---|
| Flavan-3-ol (flavonoid) | Epicatechin gallate (ECG) (8) | Inhibition of viral adsorption. | — |
| Flavonol (flavonoid) | Galangin (11) | Inhibition of viral adsorption. | — |
| Flavonol (flavonoid) | Quercetin (19) | Inhibition of the expressions of HSV proteins (gD, ICP0) and genes (ICP0, UL13, UL52). Additionally, this molecule suppressed the expression of TLR-3 and inhibited the transcriptional factors NF-κB and IRF3. | — |
| Flavonoid | Houttuynoid A (21) | Blocking viral membrane fusion. | — |
| Phenolics | kuwanon C (22), kuwanon T (23), kuwanon U (24), kuwanon E (25), and ethyl 2,4-dihydroxybenzoate (37) | Inhibition of HSV-1 and HSV-2 replication (in vitro) and inactivation of HSV-1 DNA polymerase and HSV-2 protease (proposed as competitive inhibitors via in silico assay). | Hydroxyl, carbonyl, and methyl groups along with phenyl ring (proposed as functional groups via in silico assays). |
| Alkyl derivatives of gallic acid | Octyl gallate (39) | Inhibition of multiplication of HSV-1 and suppression of formation of virus progeny at early stages (within 6 h post-infection) in the infected cells. | Alkyl moieties. |
| Tannins | Chebulagic acid (40) and chebulinic acid (41) | Avoiding the attachment and penetration of HSV-2 into Vero cells. | — |
| β-orcinol depsidone, a type of phenolic compound | Psoromic acid (45) | Inhibition of HSV-1 and HSV-2 replication and inactivation of HSV-1 DNA polymerase (competitive inhibitor via in vitro and in silico experiments). Also, via in silico assay, inactivates HSV-2 protease (competitive inhibitor). | Hydroxyl, carbonyl, and methyl groups along with phenyl ring (proposed as functional groups via in silico assays). |
| Stilbene derivative | Kuwanon X (51) | Anti-HSV activity through multiple modes of action (impeded cellular adsorption and penetration of HSV-1 viral particles). After viral penetration, this agent decreased the expression of HSV-1 IE and L genes and diminished the synthesis of HSV-1 DNA. Moreover, this molecule prevented the HSV-1-induced nuclear factor (NF)-κB activation via obstructing the nuclear translocation and DNA binding of NF-κB. | — |
| Flavonoid | Curcumin (56) | Inhibition of adsorption and replication of HSV. | Hydroxyl groups (assessed as functional groups). |
| Alkaloid | Harmine (59) | Inhibition of viral protein expression. | — |
| Monoterpenoid | Geraniol (62) | Inhibition of HSV-2 replication (in vitro assay) and inactivation of HSV-2 protease (in silico assay). | Hydroxyl and methyl groups (proposed as functional groups via in silico assay). |
| Steroids | Halistanol sulfate (96) and halistanol sulfate C (97) | Suppression of HSV-1 attachment and penetration into the host cells. These substances also impair the levels of ICP27 and gD proteins of HSV-1. | Sulfate groups (assessed as functional groups). |
| Triterpene glycoside | Glycyrrhizic acid (98) | The compound was detected to be an effective inducer of the autophagy activator Beclin 1, which creates a resistance to HSV-1 replication. | Carboxyl and hydroxyl groups along with sugar moiety (assessed as functional groups). |
| Triterpenoid | Methylester of glycyrrhetic acid (102) | Inhibition of HSV-1 replication. | Methoxy and carboxy groups at C-20 were noted to be responsible for the enhanced inhibitory activity against HSV-1 replication. |
| Pentacyclic triterpenoid | Oleanolic acid (103) | Inhibition of HSV-1 and HSV-2 multiplication at the early stage. | — |
| Spiroketal-enol ether derivative |
(E)-2-(2,4-hexa-diynyliden)-1,6-dioxaspiro[4.5]
dec-3-ene (111) |
Suppression of viral gene expression and reduction of viral protein accumulation within infected cells. |
— |
| Taxol derivatives | Methyl (N-benzoyl-(2′R,3′S)-3′-phenylisoserinate) (113) and N-benzoyl-(2′R,3′S)-3′-phenylisoserine (114) | Inhibition of HSV-1 replication (the inhibitory activity might be related to the impact on the mitotic division). | — |
| Polysaccharides | Polysaccharides and sulfated polysaccharides | Multiple mechanisms of action (inhibition of HSV replication, inhibition of virus adsorption, suppression of gene expression, suppression of HSV attachment and penetration into the host cell). | Sugar moieties and sulfate groups. |
| Cyclic peptide | Subtilosin | This antiherpetic agent alters the late stages of the viral replicative cycle such as viral glycoprotein intracellular transport. | — |
| Peptide | Griffithsin | Blocking viral entry by attaching with HSV-2 glycoprotein D. | — |
This table digests the most promising bioactive natural products that have been shown to possess potent anti-HSV activity based on their mechanisms of action, types of inhibition, and SAR, which have been displayed in this review. SAR: Structure–activity relationship that signifies functional groups which are responsible for the improved anti-HSV activity. (—): Data not provided in the articles that have been cited in this review.