Isatin-β-thiosemicarbazone is a potent anti-poxvirus agent (including monkeypox virus, orthopoxvirus, vaccinia virus, etc). Isatin-β-thiosemicarbazone also is a potent herpes simplex virus (HSV) inhibitor. Isatin-β-thiosemicarbazone exhibits
Lactoferrin is a substance released by neutrophils. Lactoferrin is an orally active multifunctional iron binding glycoprotein. Lactoferrin prevents cell adhesion, growth and spreading of cell colonies. Lactoferrin also has antiviral activity and inhibits microbial and viral adhesion and entry into host cells. Besides, Lactoferrin has anti-inflammatory, immunomodulatory, and anti-cancer activities[1][2][3].
AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3].
Vidarabine is an antiviral drug which is active against herpes simplex and varicella zoster viruses.Target: DNA/RNA SynthesisVidarabine is a nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia VIRUS and varicella zoster virus [1].
Valomaciclovir stearate (ABT 606), a nucleoside analog, is the Omaciclovir (HY-116174) prodrug. Valomaciclovir stearate has antiviral activity against HSV-1 and varicella zoster virus (VZV)[1].
2-Deoxy-D-glucose-13C-1 is the 13C 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].
5-Nitrobarbituric acid is a herpes simplex virus type-1 (HSV-1) inhibitor (IC50=1.7 μM)[1].
Ganciclovir (INN) is an antiviral medication used to treat or prevent cytomegalovirus (CMV) infections. Ganciclovir is a synthetic analogue of 2′-deoxy-guanosine. It is first phosphorylated to ganciclovir monophosphate by a viral kinase encoded by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently, cellular kinases catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate, which is present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells than uninfected cells. A prodrug form with improved oral bioavailability (valganciclovir) has also been developed.
Stearyl gallate is an alkyl gallate with a long alkyl chain (carbon number of 18). Stearyl gallate has an antioxidant activity, and a weak antiviral activity against HSV-1[1][2].
HSV-1/HSV-2-IN-1 (compound 7d) is a HSV-1 and HSV-2 inhibitor, with EC50s of 7.6, 7.6, 4, and 12 μM for HSV-1 (KOS), HSV-2 (G), HSV-1 TK- KOS ACVr and vaccinia virus in human embryonic lung fibroblast cell cultures[1].
Penciclovir (VSA 671) sodium is a potent and selective anti-herpesvirus agent with EC50 values of 0.5, 0.8 µg/ml for HSV-1 (HFEM), HSV-2 (MS), respectively. Penciclovir sodium shows anti-herpesvirus activity with no-toxic. Penciclovir sodium preventes mortality in mouse[1][2].
Cangorinine E-1 (compound 11) is a dihydroagarofuran derivative of the sesquiterpenoid family. Cangorinine E-1 exhibits weak inhibitory effects on herpes simplex virus type II (HSV)[1].
Imiquimod-d9 is deuterium labeled Imiquimod. Imiquimod (R 837), an immune response modifier, is a selective toll like receptor 7 (TLR7) agonist. Imiquimod exhibits antiviral and antitumor effects in vivo. Imiquimod can be used for the research of external genital, perianal warts, cancer and COVID-19[1][2].
HSV-1/HSV-2-IN-2 is a HSV-1, HSV-2 and VV inhibitor with EC50 values of 6.8, 8.9 and 8.9 µM, respectively. HSV-1/HSV-2-IN-2 shows antiviral activity[1].
9-Carboxymethoxymethylguanine is the main metabolite of Aciclovir. Acyclovir (Aciclovir) is a guanosine analogue and an orally active antiviral agent[1].
Netivudine is a nucleoside analogue with potent anti-varicella zoster virus activity.
FIT-039 is a selective, ATP-competitive and orally active CDK9 inhibitor with an IC50 of 5.8 μM for CKD9/cyclin T1. FIT-039 does not inhibit other CDKs and other kinases. FIT-039 inhibits replication of HSV-1 (IC50 of 0.69 μM), HSV-2, human adenovirus, and human CMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistant HSVs and other DNA viruses.
Ganoderone A is a triterpene compound that can be isolated from the fruiting body of Ganoderma pfeifferi and Ganoderma calidophilum. Ganoderone A has antiviral activity against HSV with IC50 value of 0.3 µg/mL. Ganoderone A has potential applications in viral infections and tumors[1][2][3].
Idoxuridine is an antiviral agent for feline herpesvirus type-1 with IC50 of 4.3 μM.Target: herpesvirus type-1Idoxuridine is mainly used topically to treat herpes simplex keratitis. Epithelial lesions, especially initial attacks presenting with a dendritic ulcer, are most responsive to therapy, while infection with stromal involvement are less responsive. Idoxuridine is ineffective against herpes simplex virus type 2 and varicella-zoster.
Trifluridine-13C,15N2 is the 13C and 15N labeled Trifluridine[1]. Trifluridine (Trifluorothymidine;5-Trifluorothymidine;TFT) is an irreversible thymidylate synthase inhibitor, and thereby suppresses DNA synthesis. Trifluridine is an antiviral drug for herpes simplex virus (HSV) infection. Trifluorothymidine also has anti-orthopoxvirus activity[2].
Z-LVG-CHN2 is a cell-permeable and irreversible inhibitor of cysteine proteinase. Z-LVG-CHN2 is a tripeptide derivative and mimics part of the human cysteine proteinase-binding center. Z-LVG-CHN2 displays an inhibition on HSV whereas no significant effect on poliovirus replication. Z-LVG-CHN2 effectively blocks SARS-COV-2 replication (EC50=190 nM) via inhibition of SARS-COV-2 3CL pro protease[3].
Oxytetracycline hydrochloride is an antibiotic belonging to the tetracycline class. Oxytetracycline hydrochloride potent inhibits Gram-negative and Gram-positive bacteria. Oxytetracycline hydrochloride is a protein synthesis inhibitor and prevents the binding from aminoacil-tRNA to the complex m-ribosomal RNA. Oxytetracycline hydrochloride also possesses anti-HSV-1 activity[1][2][3].
Abyssinone V is a prenylated flavonoid with predicted anti-viral activity. Abyssinone V can be isolated from the stem bark of Erythrina melanacantha. Abyssinone V possesses good pharmacodynamics properties. Abyssinone V is predicted to be antivirals including anti-herpes (HSV) agent, with mechanisms comprising inhibition of polymerase, ATPase and membrane integrity[1][2].
Valacyclovir hydrochloride is an antiviral drug used in the management of herpes simplex, herpes zoster, and herpes B. Target: HSVValacyclovir is an antiviral drug used in the management of herpes simplex, herpes zoster, and herpes B. VACV uptake was concentration dependent and saturable with a Michaelis-Menten constant and maximum velocity of 1.64 +/- 0.06 mM and 23.34 +/- 0.36 nmol/mg protein/5 min, respectively. A very similar Km value was obtained in hPEPT1/CHO cells and in rat and rabbit tissues and Caco-2 cells, suggesting that hPEPT1 dominates the intestinal transport properties of VACV in vitro . For treatment of a first episode of genital herpes, a large comparative trial has shown that valacyclovir (1 g twice a day) is as effective as acyclovir (200 mg five times a day) when given for 10 days. For treating recurrences, two trials show that valacyclovir is as effective as acyclovir (200 mg five times a day) with a treatment period of 5 days. A daily dose of 1 g of valacyclovir is as effective as 2 g daily. Valacyclovir can be administered once a day. The concentrations of acyclovir in serum and CSF were measured at steady state after 6 days of oral treatment with 1,000 mg of valacyclovir three times a day. EC50 values of PE and AC in 3T3 cells were 0.02 and 0.01 ug/ml, while values in BHK cells were 0.2 and 0.03 ug/ml. Treatment of infected immunosuppressed mice and FA and VA (b.i.d., 5.5 days) reduced the proportion with erythema from 100% to 24% and 38%, and eliminated ear paralysis, ear lesions (vesicles, etc) and death. Virus was absent from ear and brainstem by day 6, but reappeared after discontinuation in mice treated with VA.
Ganciclovir (BW 759) sodium, a nucleoside analogue and an orally active antiviral agent, shows activity against CMV. Ganciclovir sodium also has activity in vitro against members of the herpes group and some other DNA viruses. Ganciclovir sodium inhibits the in vitro replication of human herpes viruses (HSV 1 and 2, CMV) and adenovirus serotypes 1, 2, 4, 6, 8, 10, 19, 22 and 28. Ganciclovir sodium has an IC50 of 5.2 μM for feline herpesvirus type-1 (FHV-1)[1][2][3].
Valacyclovir is an antiviral drug used in the management of herpes simplex, herpes zoster, and herpes B. IC50 Value: 2.9 microg/ml (for HSV-1 W)[4]. Target: HSV infectionin vitro: VACV uptake was concentration dependent and saturable with a Michaelis-Menten constant and maximum velocity of 1.64 +/- 0.06 mM and 23.34 +/- 0.36 nmol/mg protein/5 min, respectively. A very similar Km value was obtained in hPEPT1/CHO cells and in rat and rabbit tissues and Caco-2 cells, suggesting that hPEPT1 dominates the intestinal transport properties of VACV in vitro [5]. in vivo: For treatment of a first episode of genital herpes, a large comparative trial has shown that valacyclovir (1 g twice a day) is as effective as acyclovir (200 mg five times a day) when given for 10 days. For treating recurrences, two trials show that valacyclovir is as effective as acyclovir (200 mg five times a day) with a treatment period of 5 days. A daily dose of 1 g of valacyclovir is as effective as 2 g daily. Valacyclovir can be administered once a day[1]. The concentrations of acyclovir in serum and CSF were measured at steady state after 6 days of oral treatment with 1,000 mg of valacyclovir three times a day [2]. EC50 values of PE and AC in 3T3 cells were 0.02 and 0.01 ug/ml, while values in BHK cells were 0.2 and 0.03 ug/ml. Treatment of infected immunosuppressed mice and FA and VA (b.i.d., 5.5 days) reduced the proportion with erythema from 100% to 24% and 38%, and eliminated ear paralysis, ear lesions (vesicles, etc) and death. Virus was absent from ear and brainstem by day 6, but reappeared after discontinuation in mice treated with VA [3].Clinical trial: Evaluation of Valaciclovir in Patients with Chickenpox. Phage3
Tromantadine hydrochloride, an Amantadine derivative with antiherpetic activity, inhibits herpes simplex virus type 1 (HSV-1) and HSV-2 replication[1].
HSV-1 Protease substrate is a peptide substrate for HSV-1 (Herpes Simplex Virus Type 1) protease, and the specificity constant (kcat/Km) at pH 7.5 for cleavage is 5.2 M-1 s-1[1].
Epipodophyllotoxin acetate (4-O-Epipodophyllotoxinyl acetate; compound 4) is a cyclolignan that exhibits antineoplastic and antiviral activities. Epipodophyllotoxin acetate inhibits HSV and VSV, with IC50s of 0.2 and 0.1 μg/mL, respectively[1].
Zerumbone is a monocyclic sesquiterpene compound isolated from the rhizomes of Zingiber zerumbet Smith. Zerumbone potently inhibits the activation of Epstein-Barr virus with an IC50 of 0.14 mM. Zerumbone has anti-cancer, antioxidant, anti-inflammatory and anti-proliferative activity[1][2].