THERAPEUTIC FOR INFECTIONS CAUSED BY RNA VIRUSES

Treatment for Diseases caused by Rotavirus, Influenza and Human Immuno-deficiency Virus

Therapeutic RNA Virus Inhibitor (RVI) is developed by Ophidia Products, Inc. is available for licensing for the treatment of the infections caused by RNA viruses such as rotavirus, influenza and HIV viruses. We are pleased to state that the therapeutic Oxynor for wound healing and Adesh for neurological disorders are licensed out. We are willing to give patent, technology, licensing and marketing rights in exchange for up front payment with appropriate mile stone payments, each phase during clinical trials and then royalties. All terms are negotiable.
For further information please contact:
Dr. Binie V. Lipps, President.

Patent filed for synthetic RVI (© RVI).
If required, the sequence for RVI can be disclosed by signing a confidential agreement.

Research Reports:

"Nontoxic Inhibitor to RNA Viruses Isolated from the Venom of Australian Taipan Snake", Acta Virologica 2002, in print

RNA virus inhibiting (RVI) protein is isolated from venom of the poisonous snake Australian taipan, (Oxyuranus scutellatus). Initially, RVI was tested by NCI for different strains of immunodeficiency virus responsible for causing AIDS, and was characterized as a potent inhibitor of HIV-1 and HIV-2 viruses in cell cultures. A concentration of RVI as low as 5 ng/ml inhibits the replication of HIV viruses in CEM-SS cells as well as in peripheral blood mononuclear cells and monocyte/macrophages. Furthermore, RVI inhibits various reverse transcriptase mutants of HIV-1, including AZT and non-nucleoside reverse transcriptase mutant viruses. RVI is non toxic to normal cells in concentrations up to 100 µg/ml. RVI is characterized as a stable, non toxic component of venom, having molecular weight 13.5 kDa. The sequence of the first fifteen amino acids from the N-terminal of RVI matches to phospholipase A2 from Naja n. kaouthia specie, which does not show HIV inhibitory activity. Hence this particular protein is unique for its property.

Purified RVI was tested by the NCI under the anti-AIDS testing program and concluded that it is a potent HIV inhibitor. RVI is also capable of inhibiting the virus replication of HIV strains resistant to the AZT drug. The results are presented in table I.

Table 1
Showing inhibition of p24 (IC50) synthesis in monocyte/macrophages at a concentration of 6x10^-3 µg/ml versus HIV strains

The results of table 1 clearly show that RVI is a potent inhibitor of p24 of various types of strains of HIV. p24 is a core protein of HIV and the replication of the virus can not proceed without p24. Thus RVI is a potent inhibitor of HIV replication; and it has potential for human therapy for AIDS.

Infections caused by RNA viruses: Rotavirus a double stranded RNA virus causes diarrheal disease, especially in children and until to-date there is no specific treatment. Rotavirus is implicated in infant diarrhea and the disease has great impact in developing countries. The burden of rotavirus diarrhea in United States for ages 1 to 4 is estimated to include over one million cases and up to 150 deaths per year.

Paramyxoviruses are single stranded RNA viruses include the most important agents of respiratory infections of infant and children. Those are syncytial virus (RSV) and parainfluenza virus (PIV). Recently, RSV has been identified as an important cause of lower respiratory tract infection in adults. No vaccine is currently available to prevent RSV infections. The utilization of ribovirin the only approved drug to treat RSV infections is controversial.

Conversion of Natural RVI to Synthetic Version: We realize that the natural product specially coming from snake venom will have resistance from FDA. Furthermore, production will depend on the availability of venom. By our proprietary technology and pains taking complicated research, RNA virus inhibiting domain was identified for natural venom derived RVI. Synthetic peptide consisting of ten amino acids was made and designated as syn. RVI.

Comparison between Natural and Synthetic RVI Infectivity Inhibition for RNA Viruses: For comparison, the natural and the synthetic RVI were tested in cell cultures infected with different RNA viruses. The cell line MA 104 was used for infecting simian rotavirus SA 11 strain. HEp2 cells were used for infecting respiratory syncytial virus (RSV) and para influenza virus (PIV). 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 control, group two received medium containing 10 µg/ml of natural RVI and the remaining group the medium was incorporated with 10 µg/ml synthetic RVI. The tests were read after six days and TCID/50 were calculated from cytopathic effects (CPE). The results are seen in table 2.

Table 2
Log Inhibition of infectivity in the presence of Natural RVI and Synthetic RVI at the concentration of 10 µg/ml

The results of table 2 clearly show the inhibition of infectivity of rotavirus, RSV and PIV3 viruses in presence of syn. RVI was comparable to the nat. RVI. Log TCID₅₀ for rotavirus was 6.2 and with nat.RVI and syn.RVI were 4.1 and 4.3 respectively. Giving the log TCID₅₀ infectivity inhibition 2.1 and 1.9 respectively. Log TCID₅₀ infectivity inhibition for PIV3 virus in Hep2 cells was 2.3 for nat. RVI and 2.0 for syn. RVI.

The approved drug ribovirin was tested for RSV virus in HEp2 cells at 10 µg/ml concentration. The results showed that log TCID₅₀ for RSV with ribovirin was 5.4, with nat. RVI 5.5 and with syn. RVI was 5.8. Thus the reduction in infectivity for RSV was almost similar to ribovirin and syn-RVI at 10 µg/ml concentration, however ribovirin is toxic and not suitable for human use. Syn. RVI can be made more inhibitory by increasing the concentration, as is non toxic.

By the time we discovered the active domain of the natural RVI and converted to the synthetic version of RVI the anti-AIDS testing program at the NCI was discontinued. Ophidia does not have facilities to carry AIDS virus work, therefore, synthetic version of RVI is not tested for HIV virus. However, we believe that because synthetic RVI is inhibitory to other RNA viruses it should be also for HIV.

Some of the Claims for: © RVI

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

2.The synthetic peptide RVI mimics the biological properties of the intact natural RVI, particularly in regards to inhibition of infectivity of RNA viruses including HIV in cell cultures.

3.Synthetic RVI has potential for treatment of infections or diseases caused by RNA viruses, such rotavirus, influenza viruses, RSV and HIV.

4.Synthetic RVI can be given orally for diarrhea caused by rotavirus and given as nasal spray for the infections caused by RSV and influenza viruses. It can be administered by injections for AIDS.