A METHOD FOR TREATING VIRAL DISEASES AND OTHER DISORDERS BY ALTERING IMMEDIATE GENE EXPRESSION THROUGH ADMINISTRATION OF PEPTIDE T

Abstract: A method for inhibiting viral replication and for treating neurotropic conditions by regulating/inhibiting immediate early gene expression in host cells comprises administrating an inhibiting/regulating effective amount of a peptide of formula (I): R<a>-Ser-Thr-Thr-Thr-Asn-Tyr-R<b> where R<a> represents an amino terminal residue Ala- or D- Ala and R<b> represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an additional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of formula (II): R1-R2-R3-R4-R5 where R1 is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, Ile- or Leu-, R2 is Thr, Ser, or Asp, R3 is Thr, Ser, Asn, Arg, Gln, Lys, or Trp, R4 is Tyr and R5 is preferably a carboxy terminal residue -Thr, -Arg or Gly or a derivative thereof with a corresponding D-amino acid as the amino terminal residue, and/or a corresponding amide derivative at the carboxy terminal residue and/or additionally a Cys- residue at one or both of the amino and carboxy terminals, in a physiologically suitable carrier.

Description: A Method for Treating Viral Diseases And Other Disorders By Altering Immediate Gene Expression Through Administration Of Peptide T Cross Reference To Related Application This application claims priority In U.S. Provisional Patent application No. 60/164,363 filed November 9, 1999. Technical Field This invention relates to an antiviral treatment that inhibits viral replication by altering immediate gene expression in infected cells, and also to a method for regulating immediate gene expression as a treatment for other disorders. Background Peptide T and its analogs has been found helpful in counteracting some of the symptoms of AIDS, by inhibiting the binding of HIV antigen to CD4 receptors. See U.S. Patent Nos. 5,863,718, 5,834,429 and 5,276,016. In addition, Peptide T has been found to be useful in treating various other diseases and conditions, typically due to its receptor binding ability. Peptide T has also been suggested to inhibit gpl20 induced increases in somatostatin that may effect the release of growth hormone releasing hormone. An important area of interest in treating viral diseases is the ability to inhibit viral replication. Mammalian viruses typically have immediate early genes which are necessary for subsequent transcription activation from other viral promoter elements. For example, in herpes simplex infection, immediate early genes are defined by their transciption after infection in the presence of inhibition of protein synthesis. The immediate early genes ensure efficient transcription of the viral DNA genome immediately upon entry into the cell. Infection with many viruses leads to an inhibition of transcription of cellular protein coding genes. Expression of immediate early gene products is then followed by the expression of proteins encoded by early and then late genes, including structural proteins as well as proteins necessary for viral reproduction. As an example, JC virus uses a temporal pathway where synthesis of virus encoded proteins is divided into the expression of early and late genes based on their temporal expression. The expression of late viral genes and DNA replication are under the control of the virus encoded early gene T-antigen. T antigen expression occurs early in the virus cycle under control of the viral enhancer/promoter region. Synthesis of T antigen then initiates viral DNA replication and late gene expression that encodes the virus capsid proteins. Host cell immediate early genes (IEG's) are expressed early in the cell's response to a variety of stimuli, including infection. Many IEG's are nuclear transcription factors which control transcription of host cell genes that constitute early-delayed and late gene responses to the initial stimulus. Nuclear transcription factors involved in the immediate early response are preformed and exist in a cellular pool that can be mobilized without requiring protein synthesis. This allows the cell to respond without the delay that would be incurred if gene transcription and translation were required before the IEG proteins were available. In addition, the lack of required gene transcription and translation allows for temporal control of host cell responses by depletion of transcription factors from the cellular pool. In some physiologic and pathological situations, new transcription and translation of IEG transcription factors allows prolonged up- regulation of expression of delayed-immediate and late response genes. Immediate early genes also play a role in a number of neurological and other disorders. IEG'S serving as host cell transcription factors can alter host cell responses to extra cellular signals. IEG's have been implicated in many of the changes in nervous system function mediated by neurotransmitters, neuromodulators and hormones, and IEG's may be influenced by drug induced changes. For example, long term potentiation in the hippocampus that is essential for long term memory has been shown to follow induction of IEG'S in hippocampal neurons. Several hormonal induced changes in the brain are mediated by IEG'S. For example, c-fos and c-jun are involved in the growth hormone induced release of neuropeptide Y and somatastatin. Binding of neurotransmitters and/or neuromodulators to dendrites or the neuronal cell body results in changes in IEG's expression which in turn alters the neuronal gene expression. Trans- synaptic regulation of gene expression is also mediated by induction of IEG expression. IEG's, mediate expression of early-delayed and late gene expression in the post-synaptic neuron. IEG's have also been implicated in the pathophysiologic response to cell injury, due to ischemic infarction and immunomodulators. IEG responses have been shown to be important in host cell responses to ischemia and infarction secondary to vascular occlusion. Systemic administration of immunomodulators such as lipopolysaccharide, results in expression of c-fos, c-jun and egr family of IEG transcription .factors in the hypothalamus, amygdala, and pituitary gland. These findings suggest that the behavioral responses to immune responses may be the result of immunomodulator induced IEG expression in the limbic system. A central role for IEG's in apoptosis appears to be a major pathway for cell death in neurodegenerative disorders. IEG's appear to be involved in the regulation of neurothrophic factor expression in the nervous system. Neurotrophic factors play a significant role in other diseases of the nervous system including stroke, autoimmune disorders, nerve regeneration, and possibily infections. As some examples, down-regulation of neurotrophic factor expression has also been demonstrated in several degenerative diseases of the human nervous system including Alzheimer's disease, Hunington's chorea, and spinal muscular atrophy. Alterations in the expression of severe neurothrophic factors occur in temporal lobe epilepsy, the most common adult seizure disorder. Circulating hormones have been found to regulate neurotrophic factor expression and release by glial cells and neurons. NGF, BDNF and NT3 expression is up-regulated by growth hormone and cortisol. Preliminary experiments suggest that thyroid hormone may also control neurotrophic factor expression. Egr-3, and possibly Egr-1, are involved in the regulation of BDNF expression by rat astrocytes in vitro. Agents that can halt, inhibit or alter virus induced immediate early gene expression would likely provide a potent weapon against viral infection. Even if not fully preventing replication, by at least slowing the replication process, other treatment modalities and the host immune responses can have an improved potential in destroying the viruses before replication. Further, as IEG's are implicated in so many different physiologic or neurologic disorders and in normal brain and immune functions, an agent that can alter the concentration, temporal expression, or types of IGE's expressed by the cell holds considerable promise as a therapeutic agent in a variety of neurologic diseases and other disorders. Summary of the Invention It is an object of this invention to provide a method for treating viral diseases by altering/inhibiting immediate early gene expression in infected cells. It is another object to alter IEG's expression in immune cells to regulate host immune response to provide a means for augmenting the protective immune response and/or preventing harmful immune response. It is thus another object of the present invention to provide a method for treating autoimmune diseases/disorders. It is another object to counteract various illnesses and disorders such as long term memory loss resultant from disruption of immediate early gene expression. These and other objects are achieved by the the administration of peptide T which inhibits immediate early gene expression initiated by viral infection. Administration of peptide T further up-regulates the expression of host cell IEG's that express proteins that block virus induced upregulation of viral IEG's. More specifically, the invention is a method of treating viral diseases, illnesses and disorders having symptoms resulting from a temporal pathway beginning with immediate early gene expression by regulating or inhibiting immediate early gene expression comprising administering an immediate early gene regulatory effective amount of peptide T of formula (I): R a -Ser-Thr-Thr-Thr-Asn-Tyr-R b where R a represents an amino terminal residue Ala- or D- Ala and R represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an additional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of the formula (II): R1-R2-R3-R4-R5 where Rl is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, He- or Leu-, R2 is Thr, Ser, or Asp, R3 is Thr, Ser, Asn, Arg, Gin, Lys, or Trp, R4 is Tyr and R5 is preferably a carboxy terminal residue -Thr, -Arg or Gly or a derivative thereof with a corresponding D-amino acid as the amino terminal residue, and/or a corresponding amide derivative at the carboxy terminal residue and/or additionally a Cys- residue at one or both of the amino and carboxy terminals. Brief Description Of The Drawings Fig. 1 is a graph showing c-jun expression in peptide T treated cells. Fig. 2 is a graph showing c-jun expression in peptide T treated cells and infected/treated cells. Fig. 3 is a graph showing c-jun expression in control and infected cells. Fig. 4 is a graph showing c-jun expression in peptide T treated cells. Fig. 5 is a graph showing egr-1 expression in peptide T treated cells. Fig. 6 is a graph showing egr-1 expression in control and infected cells. Fig. 7 is a graph showing egr-1 expression in peptide T treated cells and infected/treated cells. Detailed Description of the Invention For purposes of this application, the term "Peptide T" shall mean peptides with high threonine content and specifically, this invention is directed to a peptide of the formula (I): R a -Ser-Thr-Thr-Thr-Asn-Tyr-R b where R a represents an amino terminal residue Ala- or D- Ala and R b represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an additional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of the formula (II): R1-R2-R3-R4-R5 where Rl is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, He- or Leu-, R2 is Thr, Ser, or Asp, R3 is Thr, Ser, Asn, Arg, Gin, Lys, or Trp, R4 is Tyr and R5 is preferably a carboxy terminal residue -Thr, -Arg or Gly or a derivative thereof with a corresponding D-amino acid as the amino terminal residue, and/or a corresponding amide derivative at the carboxy terminal residue and/or additionally a Cys- residue at one or both of the amino and carboxy terminals, though it is known that the amino acid at the R5 position may vary widely. Most preferred are octapeptides of the following formula(I): D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr, D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr- amide, and the following pentapeptides of formula(II): Thr- Asp- Asn- Tyr- Thr, Thr- Thr- Ser- Tyr- Thr, and, Thr- Thr- Asn- Tyr- Thr, . and their analogues with D- Thr as the amino terminal residue and/or an amide derivative at the carboxy terminal. The compounds of the invention may be beneficially modified by known methods to enhance passage across the blood-brain barrier, improve stability and/or oral availability. The inventive method involves treating diseases and conditions by regulating immediate early genes by administering an effective amount of peptide T of formula(I): R a -Ser-Thr-Thr-Thr-Asn-Tyr-R b where R a represents an amino terminal residue Ala- or D- Ala and R b represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an additional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of the formula (II): R1-R2-R3-R4-R5 where Rl is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, He- or Leu-, R2 is Thr, Ser, or Asp, R3 is Thr, Ser, Asn, Arg, Gin, Lys, or Trp, R4 is Tyr and R5 is preferably a carboxy terminal residue -Thr, -Arg or Gly or a derivative thereof with a corresponding D-amino acid as the amino terminal residue, and/or a corresponding amide derivative at the carboxy terminal residue and/or additionally a Cys- residue at one or both of the amino and carboxy terminals. The method may further utilize a peptide selected from the group consisting of D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr, D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr- amide, Thr- Asp- Asn- Tyr- Thr, Thr- Thr- Ser- Tyr- Thr, and Thr- Thr- Asn- Tyr- Thr. The peptide can be administered daily at from 0.03-50 mg/kg of body weight, and be formulated for oral, buccal, parenteral, topical, rectal, transdermal or intranasal administration. In one embodiment, the peptide is administered daily and parenterally at from 0.2-10 mg/kg for a 70 kg human, and can be administered in a single dose or multiple doses. For purposes of regulating/inhibiting immediate early gene expression, levels at 10 "9 molar peptide T concentrations in tissue culture may be appropriate. In the whole animal, dosage of about 0.1 to 500 mg/Kg would be administered. The amounts needed will be partly determined by the age and condition of the patient. The peptide T may be delivered parenterally,. especially intravenously or intrathecally. However, it may also be administered transdermally in carriers such as DMSO or by patch. Peptide T may be dried and administered intranasally by being snorted, administered as a nasal spray or given rectally. The composition of the invention is normally formulated in a physiologically acceptable carriers or excipients, and the composition may contain from 0.001-99% of the peptide T. These compositions may also contain other active ingredients, such as antimicrobials, and the invention is not limited in this way. They may also be formulated as powders, granules, tablets, suspensions, solutions, or emulsions, and contain the ingredients known in the art for preparing such formulations, and may be packaged in single or multidose form. The following experiments demonstrate that Peptide T alters EEG expression in both JC virus infected and un-infected U87MG cells. The results of these experiments, which are described below, provide support for the the likely effects of Peptide T in other disease treatments by regulating IEG expression. c-jun expression in JC virus infected and un-infected U87MG cells. Expression of c-jun was first examined in uninfected U87MG cells, a glial cell line. To this end, U87MG cells were cultured in media containing Peptide T at 10 and 0.01 μg/ml. Cells were harvested, nuclei lysed and nuclear proteins collected by the method of Dingham. U87MG cells sham treated and cultured in media without Peptide T served as controls. Results of these experiments are shown in Figure 1 Peptide T at both 10 and 0.01 μg/ml resulted in down-regulation of c-jun protein expression at 4 hours. A dose response effect was noted with Peptide T at 10 μg/ml resulting in the greatest decrease in c-jun protein expression. By 16 hours, un-infected U87MG cells expressed the same levels of c-jun in Peptide T treated and sham treated cultures. Thus, the alteration in c-jun protein expression by Peptide T in un-infected U87MG cells was transient. JC virus infection of U87MG cells results in an initial decrease in c-jun expression at 4 hours (Figure 2). Following the initial decrease in c-jun expression, c-jun expression is increased above control levels (12.5X control). Phosphorylated c-jun expression is increased above baseline as early as 2 hour. Rough total c-jun is also reduced. Phosphorylated c-jun remains elevated through 48 hours (Fig. 3). Thus, the active phosphorylated form of c-jun is up- regulated in JC virus infected glial cells. It is likely c-jun binding to the JC virus enhancer/promoter is involved in virus expression. The viral enhancer/promoter region has three JUN binding sites. One of these sites is adjacent to the NF-1D consensus sequence in the B domain of the enhancer/promoter region. NF-ID is essential for virus enhancer/promoter activity, and virus expression. The up-regulation of phosphorylated c-jun expression by JC virus provides a means by which the virus regulates it's expression. Peptide T treatment of JC virus infected U87MG cells blocks virus induced c-jun expression. To this end, JCV infected U87MG cells were treated with Peptide T at 10 μg and 0.01 μg/ml. Virus induced c-jun expression is blocked by Peptide T at both concentrations. Phosphorylated c-jun expression was suppressed up to 96 hours. (Fig. 4). Treatment with Peptide T at either 10 or 0.01 μg/ml blocks the up-regulation of c-jun expression. Analysis and interpretation: The JC virus enhancer / promoter has a number of binding sites recognized by host cell transcription factors. The experiments described above demonstrate up-regulation of c-jun expression follows JC virus infection of U87MG cells. JUN likely plays a role in modulating the JC virus enhancer/promoter activity by forming a nuclear transcription factor complex with NF- 1D, given the close proximity of the NF-ID and JUN DNA binding sites. NF-ID has been shown to be necessary but not sufficient for optimal JCV enhancer/promoter activity. The decrease in c-jun likely reduces the expression of the early enhancer/promoter which controls expression of T antigen; the pivotal virus protein which controls the virus replication. The decrease in host cell c-jun expression represents one, but likely not the only, site by which Peptide T blocks JC virus T antigen synthesis and therefore virus replication. B. egr-1 expression in JC virus infected and un-infected U87MG cells The effects of JC virus infection and Peptide T treatment on expression of the BEG erg-1 was also examined. These experiments were performed using the same experimental protocol as described for c-jun. U87MG cells were treated with Peptide T at concentrations of 10 and 0.01 μg/ml. Control cultures were sham treated with vehicle used to dissolve Peptide T in concentrations comparable to that used to dissolve Peptide T in the experimental cultures. Results are shown in Figure 5. Peptide T induced a small but significant increase in egr-1 expression in U87MG cells at 4 hours. By 16 hours, the increased egr-1 expression was suppressed compared to control cultures. These findings suggest that Peptide T induces transcription of immediate-delayed or delayed host cell genes at 4 hours. The temporal profile seen in Peptide T treated cells follows that seen with other hormone and immunomodulator stimuli of glial cells; i.e. a brisk response early with decaying of the response in a matter of hours. These findings suggest that Peptide T does not up-regulate egr-1 mRNA expression in un-infected U87MG cells. Egr-1 expression in JC virus infected U87MG cells is shown in Figure 6. JC virus infection of U87MG cells results in a decrease in egr-1 activity at 4 hours which likely represents the host cell response to virus infection by mobilization of cellular stores and binding of egr-1 to host cell DNA sequences. By 16 hours, JC virus infected cells experience a small but significant rise in egr-1 expression. JC virus infected cells U87MG cells treated with Peptide T have a marked increased expression of egr-1 at 4 hours (Fig. 7). JC virus infected U87MG cells treated with Peptide T at 10 μg/ml express less of a rise in egr-1 activity than cells treated with 0.01 μg/ml. Where virus infected U87MG cells continue to express egr-1 at 16 hours, Peptide T at both 10 and 0.01 μg/ml return to levels of egr, comparable to control U87MG cells treated with vehicle only. Analysis and interpretation: Peptide T blocks expression of egr-1 at 16 hours in JC virus infected U87MG cells. Egr- 1 expression is down-regulated early in JC virus infected cells compared to the brisk elevation in sham infected cells (control cells) treated with vehicle alone. These findings support the hypothesis that JCV infection blocks a host cell response to encountering a foreign protein, i.e. viral capsid antigen. Peptide T also induces expression of egr-1 in virus infected cells at 4 hours but not to the level of stimulated control cells. The stimulation of egr-1 in Peptide T treated cells likely results in the activation of immediate-delayed or delayed host cell genes that are part of the cellular response to infection. There are several candidate genes that could be important. The egr family of transcription factors has several members that are up-regulated at varying times. Egr-1 stimulates the synthesis of egr-3 that follows several hours after egr-1 expression. Both egr-1 and egr-3 bind the same DNA consensus sequences. Modulation of gene expression is, at least in part, the result of the different protein-protein binding properties that alter the activity of the transcription complexes of which they are a part. Other immediate-delayed and delayed genes which could be affected by alteration in egr-1 expression include immunomodulatory molecules (TL-1, IL-2, TNF-α, and TGF-β) and neurotrophic factors (BDNF, NT3, NT4/5) all of which have egr DNA consensus sequences in their enhancer/promoter regions. Egr-3 is a second member of the egr family of transcription factors involved in IEG responses. The expression of egr-3 in JC virus infected and un-infected U87MG cells was examined using the same experimental protocol as described for c-jun and egr-1. Jc virus infected cells have a transient increase in expression of egr-3 at 1 hr. post infection. Egr-3 levels return to baseline by 2 hr. post infection. Egr-3 is up regulated and sustained for 96 hours in Peptide T treated, uninfected U87MG cells. Levels of egr-3 were 10X increased in cells treated with Peptide T at 10 μg/ml. U87MG cells treated with Peptide T at 0.01 μg/ml underwent a more modest (approximately 3 fold) increase in egr-3 expression. Peptide T treated JC virus infected U87MG cells demonstrated the same sustained increase in egr-3 expression. Analysis and interpretation: The ability of Peptide T to up-regulate the expression of egr-3 appears to be independent of the presence of JC virus infection. This may be of some import since egr-3 has been implicated in host cell immune-nonspecific (interferon) and immune- specific (MHC antigen) expression. It is possible that the increased and prolonged expression of egr-3 may alter JC virus replication by up regulating host cell defenses against intracellular parasites From the above and other experiments, it is believed that: Peptide T inhibits JCV replication in vitro in both continuous and primary glial cell cultures; inhibits JCV replication, at least in part, by down-regulating the synthesis of the viral early gene, T antigen; down regulates T antigen expression to prevents the switch to DNA replication and late viral gene expression. These events are at least in part mediated by an alteration in immediate early gene expression in U87MG cells. Peptide T reduces c-jun expression at 4 hours in uninfected cells; blocks up-regulation of c-jun expression induced by JC virus infection of U87MG cells; up-regulates egr-1 expression at 4 hours and reduces egr-1 expression at 16 hours in uninfected U87MG cells; up-regulates egr-1 expression at 4 hours in JC virus infected U87MG cells and blocks egr-1 up-regulation by JC virus at 16 hours. The temporal changes seen in egr-1 expression likely alter the expression of other egr family members which are induced later in the IEG expression. C-fos expression either in JC virus infected or uninfected U87MG cells is not altered by Peptide T. It is believed that there is support for a molecular mechanism for the antiviral effects of Peptide T in JC virus infected cells which can have application to the treatment of other viral diseases. The alterations of IEG expression demonstrate Peptide T is able to signal glial cells to alter mobilization of intracellular pools of IEG proteins as well as likely blocking virus induced up-regulation of c-jun and egr-1 transcriptional activity. The immediate-delayed and delayed host cell genes altered by Peptide T are not yet known, but likely include other nuclear transcription factors (i.e. egr-3, NF-ID, etc.), immunomodulators (cytokines), and neurotrophic factors. It is believed that the molecular mechanisms of Peptide T antiviral effects on JC virus could be achieved with other viruses, which rely on host cell nuclear transcription factors for virus expression (i.e. Herpes simplex, Varicella zoster, etc.), RNA viruses which use host cell transcription factors, and RNA viruses under strict virus encoded molecular control (HTLV-1, 2 and HIV), among others. Even if Peptide T does not halt infection, it may have a synergistic effect when used with other drugs if it blocks or alters transcriptional activity of host cells. Peptide T's effects on immediate-delayed and delayed glial cell genes provides a strong possibility of treating other neurological disorders, and other illnesses. Some examples would be autoimmune disorders (multiple sclerosis), neurohormonal disorders (growth hormone deficiencies, Neuropeptide Y deficiencies, etc.) and disorders with down-regulation of neurotrophic factors, which may include, for example, Alzheimers' disease. Degenerative diseases which have underlying cell apoptosis as one of the pathogenic mechanisms are also likely to be amenable to treatment with Peptide T. While the molecular mechanism by which Peptide T alters IEG expression is unknown, if there is a reduction in mRNA levels for an IEG, it is possible that Peptide T alters gene transcription, whereas a reduction in IEG protein expression in the presence of unaltered mRNA levels would suggest that Peptide T alters IEG by blocking mRNA translation into protein. If Peptide T intervenes at the mRNA level, this would allow the use of differential, expression techniques to identify other proteins altered by Peptide T by identifying previously unknown mRNA transcript changes in drug treated cells. There is also a potential for Peptide T to treat neurohormonal disorders and the expression of neurotropic factors that are regulated by neurohormones. It is believed that Peptide T, by altering neurotrophic factor expression, could have widespread applicability to many neurological conditions with altered trophic factor expression. While preferred embodiments of the present invention have been shown and described, it will be understood by one skilled in the art that various changes or modifications can be made without varying from the scope of the present invention.

Claims: CLAIMS 1. A method for inhibiting viral replication and for treating neurotropic conditions by regulating/inhibiting immediate early gene expression in host cells comprises administrating an inhibiting/regulating effective amount of a peptide of formula(I): R a -Ser-Thr-Thr-Thr-Asn-Tyr-R b where R a represents an amino terminal residue Ala- or D- Ala and R b represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an additional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of the formula (II): R1-R2-R3-R4-R5 where Rl is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, He- or Leu-, R2 is Thr, Ser, or Asp, R3 is Thr, Ser, Asn, Arg, Gin, Lys, or Trp, R4 is Tyr and R5 is preferably a carboxy terminal residue -Thr, -Arg or Gly or a derivative thereof with a corresponding D-amino acid as the amino terminal residue, and/or a corresponding amide derivative at the carboxy terminal residue and/or additionally a Cys- residue at one or both of the amino and carboxy terminals. 2. The method of claim 1 wherein the peptide is selected from the group consisting of D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr, D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr- amide, Thr- Asp- Asn- Tyr- Thr, Thr- Thr- Ser- Tyr- Thr, and Thr- Thr- Asn- Tyr- Thr. 3. The method of claim 1 wherein the peptide is administered daily at from 0.01-500 mg/kg of body weight. 4. The method of claim 1 wherein the peptide is formulated for oral, buccal, parenteral, topical, rectal, transdermal or intranasal administration. 5. The method of claim 1 wherein the peptide is administered daily and parenterally at from 0.2-10 mg/kg for a 70 kg human. 6. The method of claim 1 wherein the peptide is administered in a single dose or multiple doses. 7. A method of treating viral infection by inhibiting viral replication by reducing virus induced c-jun, egr-1 and/or egr-3 expression in host cells comprising administering an inhibiting effective amount of a peptide of formula(I): R a -Ser-Thr-Thr-Thr-Asn-Tyr-R b where R a represents an amino terminal residue Ala- or D- Ala and R b represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an additional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of the formula (II): R1-R2-R3-R4-R5 where Rl is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, He- or Leu-, R2 is Thr, Ser, or Asp, R3 is Thr, Ser, Asn, Arg, Gin, Lys, or Trp, R4 is Tyr and R5 is preferably a carboxy terminal residue -Thr, -Arg or Gly or a derivative thereof with a corresponding D-amino acid as the amino terminal residue, and/or a corresponding amide derivative at the carboxy terminal residue and/or additionally a Cys- residue at one or both of the amino and carboxy terminals. 8. The method of claim 7 wherein the peptide is selected from the group consisting of D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr, D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr- amide, Thr- Asp- Asn- Tyr- Thr, Thr- Thr- Ser- Tyr- Thr, and Thr- Thr- Asn- Tyr- Thr. 9. The method of claim 7 wherein the peptide is administered daily at from 0.01-500 mg/kg of body weight. 10. The method of claim 7 wherein the peptide is formulated for oral, buccal, parenteral, topical, rectal, transdermal or intranasal administration. 11. The method of claim 7 wherein the peptide is administered daily and parenterally at from 0.2-10 mg/kg for a 70 kg human. 12. The method of claim 7 wherein the peptide is administered in a single dose or multiple doses. 13. A method of treating viral diseases, illnesses and disorders having symptoms resulting from a temporal pathway beginning with immediate early gene expression by regulating or inhibiting immediate early gene expression comprising administering an immediate early gene regulatory effective amount of a peptide selected from the group consisting of D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr, D- Ala- Ser- Thr- Thr- Thr- Asn- Tyr- Thr- amide, Thr- Asp- Asn- Tyr- Thr, Thr- Thr- Ser- Tyr- Thr, and Thr- Thr- Asn- Tyr- Thr.

Inventors: ADAMS MERRIBETH, FARRAND DEAN, HOUFF SIDNEY, ADAMS, MERRIBETH, FARRAND, DEAN, HOUFF, SIDNEY
Applicants: ADVANCED IMMUNI T INC, ADVANCED IMMUNI T, INC.
Application year: 2000
Main classification: A61K
IPC codes: A61K38, A61P25, A61P31, A61P37, C07K7