HHV-2 Envelope Glycoprotein G (552-574) is an immunodominant region of glycoprotein G (gG-2) reactive with all herpes simplex (HSV-2) sera[1].
BVDU 5′-Triphosphate is an antivirus agent with 5′-Triphosphate label, targeting viral DNA polymerase. BVDU 5′-Triphosphate shows excellent selectivity against varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1), due to a specific phosphorylation by the virus-encoded thymidine kinase.
Acyclovir monophosphate is a potent anti-herpes simplex virus (HSV) agent. Acyclovir monophosphate blocks DNA synthesis through the inhibition of the viral DNA polymerase and terminates the chain elongation of the viral DNA. Acyclovir monophosphate shows antitumor activity[1][2].
B220 is an antiviral agent which can inhibit the growth of HSV-1, HSV-2 and human cytomegalovirus (CMV).
Brassicasterol, a metabolite of Ergosterol, plays a role in the inhibitory effect on bladder carcinogenesis promotion via androgen signaling[1]. Brassicasterol shows dual anti-infective properties against HSV-1 (IC50=1.2 µM) and Mycobacterium tuberculosis, and cardiovascular protective effect[2]. Brassicasterol exerts an anti-cancer effect by dual-targeting AKT and androgen receptor signaling in prostate cancer[3].
Manzamine A, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits Autophagy in pancreatic cancer cells. Manzamine A has antimalarial and anticancer activities. Manzamine A also shows potent activity against HSV-1[1][2][3][4].
Gallic aldehyde is a HSV-1 inhibitor isolated from Geum japonicum, with potent antiviral activity[1].
Isoborneol ((±)-Isoborneol) is a monoterpenoid alcohol present in the essential oils of numerous medicinal plants and has antioxidant and antiviral properties. Isoborneol is a potent inhibitor of herpes simplex virus type 1 (HSV-1)[1][2].
2-Deoxy-D-glucose-d1 is the deuterium labeled 2-Deoxy-D-glucose. 2-Deoxy-D-glucose is a glucose analog that acts as a competitive inhibitor of glucose metabolism, inhibiting glycolysis via its actions on hexokinase[1][2].
Minumicrolin is a plant growth inhibitor. Minumicrolin can be isolated from Murraya paniculata. Minumicrolin inhibits Epstein-Barr virus early antigen (EBV-EA) activation[1][2].
Penciclovir is reported to be potent against HSV types 1 and 2 with IC50 of 0.04-1.8 μg/mL and 0.06-4.4 μg/mL, respectively.
Surfen dihydrochloride is a potent HS (heparan sulfate) antagonist. Surfen binds to glycosaminoglycans. Surfen neutralizes the anticoagulant activity of both unfractionated and low molecular weight heparins. Surfen affects sulfation of heparin and inhibits degradation by heparin lyases. Surfen inhibits FGF2 binding and signaling. Surfen inhibits cell attachment, and virus infection[1].
Fiacitabine(NSC 382097; FIAC; FOAC) is a selective inhibitior of DNA replication of herpes simplex virus(HSV) with IC50 values of 2.5 nM and 12.6 nM for HSV1 and HSV2, respectively. IC50 value: 2.5/12.6 nM (HSV1/2) [2]Target: HSVFIAC suppressed by 90% the replication of various strains of herpes simplex virus types 1 and 2 at concentrations of 0.0025 to 0.0126 microM. Cytotoxicity was minimal, as determined by trypan blue dye exclusion with norman Vero, WI-38, and NC-37 cell proliferation; the 50% inhibitory dose was 4 to 10 microM in a 4-day assay. FIAC was active at much lower concentrations than arabinosylcytosine, iododeoxyuridine, and arabinosyladenine. It was slightly more active against herpes simplex virus type 1 than acycloquanosine and slightly more toxic to normal cells. FIAC was about 8,000 times more active against the replication of wild-type herpes simplex virus type 1 than against a mutant strain lacking the expression of virus-specified thymidine kinase [2].
CMX001 (Brincidofovir; HDP-CDV) was developed as an orally active, lipophilic form of cidofovir (CDV); has enhanced activity in vitro and in vivo compared to CDV against certain herpesviruses, adenoviruses and orthopoxviruses.IC50 Value: 5.5 nM (EC50, in PDA at 7 dpi) [3]Target: anti-CMVCMX001 is currently in Phase II clinical studies for development as a therapeutic agent for human CMV, adenovirus and BK virus infections, as well as, for adverse events following smallpox vaccinations.in vitro: In PDA at 7 dpi, the CMX001 50% effective concentration (EC50) was 5.55 nM, the 50% cytotoxic concentration (CC50) was 184.6 nM, and the 50% selectivity index (SI50) was 33.3. The EC90 was 19.7 nM, the CC90 was 5,054 nM, and the SI90 was 256.1. In COS-7 cells, JCV replication was faster and the EC50 and EC90 were 18- and 37-fold higher than those in PDA, i.e., 0.1 μM and 0.74 μM (CC50, 0.67 μM; SI50, 6.7; CC90, 12.2 μM; SI90, 16.5) at 5 dpi [3].in vivo: CMX001 and CDV are equally efficacious at protecting mice from mortality following high ectromelia virus doses (10,000 x LD(50)) introduced by the intra-nasal route or small particle aerosol. Using CMX001 at a 10mg/kg dose followed by 2.5mg/kg doses every other-day for 14 days provided solid protection against mortality and weight loss following an intra-nasal challenge of (100-200) x LD(50) of ectromelia virus [1]. When CMX001 was administered orally to mice infected with HSV-1, mortality was reduced significantly (p≤0.001) with all three dose levels when treatments were initiated 24 h post viral inoculation. When treatments were started 48 h post viral inoculation, 5 and 2.5 mg/kg significantly reduced mortality (p≤ 0.001). If treatments were delayed until 72 h post viral inoculation, CMX001 did not reduce mortality or increase the mean day to death. When mice were infected intranasally with HSV-1 and treatments initiated 24 h post viral inoculation using CMX001 at 5 mg/kg or ACV at 100 mg/kg, virus replication in target organs was reduced by both CMX001 and ACV when compared to vehicle treated mice [2]. Toxicity: Diarrhea was the most common adverse event in patients receiving CMX001 at doses of 200 mg weekly or higher and was dose-limiting at 200 mg twice weekly. Myelosuppression and nephrotoxicity were not observed [4].
Galactofucan (Fucogalactan) is a sulfated polysaccharide. Galactofucan can be extracted from brown seaweed Saccharina longicruris with anticoagulant, anti-tumor, anti-thrombosis, anti-inflammatory and antiviral properties. Galactofucan shows antiviral activities to HSV-1 and HSV-2 with IC50s of 0.76 and 1.34 µg/mL, respectively. Galactofucan can be used for the research of cancer and inflammation[1][2].
Surfactin is a potent cyclic lipopeptide biosurfactants that mediates flux of mono-and divalent cations, such as calcium, across lipid bilayer membranes. Surfactin can act as an antimicrobial adjuvant with anti-bacterial, anti-fungal, antimycoplasma and hemolytic effects[1][2]. Surfactin also has antiviral activity against a variety of enveloped viruses[3].
GLR-19 is an anti-HIV peptide. GLR-19 also has antiviral activity against HSV-2[1][2].
LDC4297 hydrochloride is a selective inhibitor of CDK7 with an IC50 value of 0.13 nM. LDC4297 hydrochloride inhibits human cytomegalovirus (HCMV) replication with an EC50 value of 24.5 nM. LDC4297 hydrochloride shows broad antiviral activities to Herpesviridae, Adenoviridae, Poxviridae, Retroviridae and Orthomyxoviridae with EC50 values of 0.02-1.21 μM. LDC4297 hydrochloride can be used for the research of infection[1].
Isoxanthohumol is a prenylflavonoid from hops and beer. Isoxanthohumol exhibits an antiproliferative activity against several human cancer cell lines. Isoxanthohumol inhibits the development of lung metastatic foci in tumor-challenged animals. Isoxanthohumol shows an antiviral activity towards herpes viruses (HSV1 and HSV2) and bovine viral diarrhea virus (BVDV)[1][2].
OG-L002 is a potent and highly selective LSD1 inhibitor with an IC50 of 0.02 μM. OG-L002 is a potent monoamine oxidases (MAO) inhibitor with IC50s of 1.38 μM and 0.72 μM for MAO-A and MAO-B, respectively. OG-L002 potently inhibits the expression of HSV IEgenes[1].
BRL44385 is a potent and selective inhibitor of the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV2), varicella zoster virus (VZV) and Epstein-Barr virus (EBV).
2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid, a natural ursane-type triterpene, is a potent inhibitor of HIV Protease (HIV Protease). 2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid is also an inhibitor of the activation of Epstein-Barr virus early antigen (EBV-EA). 2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid displays an inhibitory activity against nitric oxide production in Lipopolysaccharide (Lipopolysaccharides)-activated RAW 264.7 cells[1][2].
Ferruginol ((+)-Ferruginol), a natural diterpenoid, is an inhibitor of the activation of Epstein-Barr virus early antigen (EBV-EA). Ferruginol inhibits the growth of thyroid cancer cells through the induction of mitochondrial Apoptosis. Ferruginol has antitumor, cardioprotective, antioxidant, gastroprotective, and neuroprotective activities[1][2][3].
Glyceryl monocaprate (Monolaurin) is a 1-monoglyceride of capric acid against gram-positive bacterial infections[1]. Glyceryl monocaprate (Monolaurin) has inhibitory effect on Herpes Simplex Virus (HSV) and offers an effective treatment for herpes labialiss[2].
BAY 57-1293 represents a new class of potent inhibitors of herpes simplex virus (HSV) that target the virus helicase primase complex.IC50 Value: 20 nM (HSV-1) [1]Target: HSVin vitro: BAY 57-1293 is nearly two orders of magnitude more potent than acyclovirin vitro and the superiority was even more prominent when the viral load was increased (BAY 57-1293 IC50 = 12 nM, 20 nM and 50 nM; acyclovir IC50 = 1uM, 3M and 10 50 uM at a multiplicity of infection (m.o.i.) of 0.0025, 0.02 and 0.2, respectively). A minor increase in IC50 values at higher viral loads was observed for all thiazolyl compounds listed in Table 1. BAY 57-1293 was also active against porcine (IC50 = 5 uM) and bovine (IC50 = 0.12 uM) herpes strains [1].in vivo: Delayed treatment with BAY 57-1293 (20 mg/kg 2× daily per os, treatment day 4-14) abrogates progression of disease symptoms (mean of 10 animals per group) of HSV-2 infected guinea pigs within 1 d of treatment and healing is observed subsequently, whereas a 7.5 fold higher dose of valacyclovir (150 mg/kg 2× daily) shows marginal therapeutic efficacy compared with placebo [1]. The compound given orally, or intraperitoneally once per day at a dose of 15 mg/kg for 4 successive days was equally effective or superior to a much higher dose of famciclovir (1mg/ml, i.e. approximately 140-200mg/kg/day) given in the drinking water for 7 consecutive days, which, in our hands, is the most effective method for administering famciclovir to mice [2].Toxicity: Exploratory toxicology and safety pharmacology studies did not reveal any safety relevant findings at 30, 100 and 300 mg/kg BAY 57-1293 (once daily per os) in a 4-week chronic toxicity study in dogs. However, administration of the same dose to rats for 4 weeks resulted in a dose-dependent transitional hyperplasia of the urinary bladder epithelium [1].
Perillic acid is the metabolite of Perillyl alcohol (HY-N7000). Perillic acid induces lung cancer cell cycle arrest and apoptosis. Perillic acid shows anti-HSV-1 and immunomodulatory activities[1][2][3].
Tromantadine is a herpes simplex virus (HSV) inhibitor.