Herpoxin for Herpes Virus Infections

Herpes, CMV, Shingles and Tuberculosis

Patent awarded

US Patent#: 5,648,339, 1997 "Herpes Virus Inhibitor and Method."
Protein Herpoxin (© HERP) Mol Wt= 13.5 kDa
Indication: Herpes, CMV & Shingles
US patent for synthetic Herp (© synHERP) is filed.

Research Reports:

"Inhibition of Herpes Viruses by a novel nontoxic protein from cobra venom", Acta Viologica 2001

Herpes simplex viruses type 1 and type 2 are double stranded DNA viruses. The clinical entities attributable to herpes virus type 1 include (1) Acute herpetic gingivostomatitis which occurs mostly in small children. (2) Eczema herpeticum, Kaposi's varicelliform eruption. (3) Keratoconjunctivitis infection of eye. (4) Herpes encephalitis, carries a high mortality rate and survivors often have residual neurological defects. (5) Herpes labialis, cold sores is the most common recurrent disease in the form of oral lesions. Herpes virus type 2 is implicated in (1) Genital herpes, herpes progenitalis is characterized by vesiculoulcerative lesions of the penis of the male or the cervix, vulva, vagina and perineum of the female. (2) Neonatal herpes- herpes type 2 may be transmitted to the newborn during birth by contact with herpetic lesions in the birth canal producing permanent brain damage.

Varicella zoster virus is a double stranded DNA virus and is morphologically identical with herpes simplex viruses. Herpes zoster commonly known as shingles is a sporadic incapacitating disease in adults, rare in children, which is characterized by an inflammatory reaction of the posterior nerve roots and ganglia, accompanied by the affected sensory nerves. Cytomegalo virus causes opportunist infection in AIDS patients. CMV infection may be transmitted to newborn with defects.

Novel protein, Herpoxin, isolated from the venom of Naja n. kaouthia snake having mol. Wt 13.5 kDa, inhibits CPE of HSV-1, HSV-2 and CMV viruses in cell cultures. Herpoxin proved to be a potential therapeutic to treat herpes virus and CMV induced oral and genital lesions including shingles caused by herpes zoster. Its use may be extended to infections caused by other DNA viruses.

Conversion of Herpoxin to Synthetic Version: By our proprietary technology active domain for natural Herpoxin was identified. Synthetic peptide consisting of ten amino acids was made.

Infectivity Inhibition of HSV-1 and HSV-2 Viruses by Synthetic Herp: For comparison, the natural and the synthetic Herps were tested in Vero cell cultures infected with HSV-1 or HSV-2 viruses. The cells were infected in serial concentrations from 102 to 108, three wells were used for each concentration. After absorption of the virus the cultures were divided into three groups. Group one received medium containing PBS as a positive control, group two received medium containing 10 µg/ml of natural Herp and the remaining group the medium was incorporated with 10 µg/ml synthetic Herp. The tests were read after six days and TCID/50 were calculated from CPE.
The results are seen in table 1.

Table 1
Log Inhibition of infectivity of HSV-1 and HSV-2 in the presence of Natural Herp and Synthetic Herp at the concentration of 10 µg/ml in Vero cells.

VirusAdditiveLogTCID50PBS-Nat HerpPBS-Syn Herp
HSV-1PBS5.2
HSV-1Nat Herp3.12.1
HSV-1Syn Herp4.01.2
HSV-2PBS7.0
HSV-2Nat Herp4.52.5
HSV-2Syn Herp5.11.9

The results of table 1 clearly show the inhibition of infectivity of HSV viruses in presence of synthetic Herp was comparable to the natural Herp. Log TCID50 for HSV-1 was 5.2 and with nat-Herp and syn-Herp 4.0 respectively. Giving the log TCID50 infectivity inhibition 1.2 and 1.9 respectively. Similarly, the inhibition in the infectivity of HSV-2 by Nat-Herp was 2.5 versus 1.9 with Syn-Herp. The inhibition of HSV viruses will be higher by increasing the concentration of syn-Herp.

Tuberculusis is a serious health problem worldwide. The causative agent is a tubercle bacillus of various strains. There are several approved drugs to treat tuberculosis. However, existing strains have become resistant to these treatments. Therefore, new drugs are needed to treat the current strains of TB.

Both Herp and synHerp consisting of ten amino acids were tested for anti-TB activity in human macrophages. Both were found to have anti-TB activity. Herp is active at 50 µg/ml and syn Herp is active at 100 µg/ml. Thus, the synthetic version of Herp has potential for TB treatment.

1. Composition of matter comprising Herp is a synthetic peptide consisting of ten amino acids mimics the biological properties of the whole natural molecule of Herp.

2. The synthetic peptide Herp mimics the biological properties of the intact natural Herp, particularly in regards to inhibition of infectivity of DNA viruses in cell cultures.

3. Synthetic Herp has potential for treatment of infections or diseases caused by DNA viruses, oral and genital legions caused by herpes viruses, HSV-1 and HSV-2.

5. Synthetic Herp can be applied topically, or by injection for treatment of infections caused by herpes viruses.

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