Use of antiviral agents, composition of matter, combination preparations/agents to treat chronic diseases associated with epstein-barr virus and other human herpes viruses

A method for treating relapsing-remitting multiple sclerosis or HLA marker DR2 (DRB1*1501) progressive multiple sclerosis, the method comprising the steps of:

• (a) administering H2G intravenously or intramuscularly at about 5 mg/kg to about 25 mg/kg twice daily for 1 day to 6 weeks with tenofovir at about 5 mg to about 150 mg in the H2G intravenous solution or administered as a separate intravenous bolus or intramuscular injection for 1 day to 6 weeks or with tenofovir disoproxil fumarate administered orally at about 10 mg to about 150 mg twice daily;
• (b) subsequently administering high-dose valomaciclovir stearate at about 1.5 g to about 2 g twice daily orally combined with tenofovir disoproxil fumarate, wherein the tenofovir disoproxil fumarate is administered separately orally or in the form of a combination tablet or capsule containing both valomaciclovir stearate and tenofovir disoproxil fumarate;
• and
• (c) subsequently administering a low dose valomaciclovir stearate therapy of about 1 g to 2 g daily orally with chronic dosing.

A method for treating relapsing-remitting multiple sclerosis or HLA marker DR2 (DRB1*1501) progressive multiple sclerosis, the method comprising the steps of:

• (a) administering H2G intravenously or intramuscularly at about 5 mg/kg to about 25 mg/kg twice daily for 1 day to 6 weeks plus low-dose interferon type 1, either Avonex (interferon beta-1a) once weekly intramuscularly at 7.5 μg once in week 1 and 15 μg once in week 2, and 30 μg once in weeks 3 and 4 or Betaseron (interferon beta-1 b) every other day subcutaneously with 0.0625 mg in week 1, 0.125 mg in week two;
• 0.1875 mg in week 3;
• and 0.25 mg in week 4;
• (b) subsequently administering high-dose valomaciclovir stearate at about 1.5 g to about 2 g orally twice daily combined with low-dose interferon type 1 therapy as described in step (a);
• and
• (c) then followed by low-dose valomaciclovir stearate orally at 1 g to 2 g once daily with chronic dosing.

A method for treating relapsing-remitting multiple sclerosis or HLA marker DR2 (DRB1*1501) progressive multiple sclerosis, the method comprising the steps of:

• (a) administering H2G intravenously or intramuscularly at about 5 mg/kg to about 25 mg/kg twice daily for 1 day to 6 weeks plus low-dose interferon type 1, either Avonex (interferon beta-1a) once weekly intramuscularly at 7.5 μg once in week 1 and 15 μg once in week 2, and 30 μg once in weeks 3 and 4 or Betaseron (interferon beta-1 b) every other day subcutaneously with 0.0625 mg in week 1, 0.125 mg in week two;
• 0.1875 mg in week 3;
• and 0.25 mg in week 4;
• and
• (b) subsequently followed by low-dose valomaciclovir stearate orally at 1 g to 2 g once daily with chronic dosing.

A method for treating relapsing-remitting multiple sclerosis or HLA marker DR2 (DRB1*1501) progressive multiple sclerosis, the method comprising the steps of:

• (a) administering H2G intravenously or intramuscularly at about 5 mg/kg to about 25 mg/kg twice daily for 1 day to 6 weeks, plus low-dose interferon type 1, either Avonex (interferon beta-1a) once weekly intramuscularly at 7.5 μg once in week 1 and 15 μg once in week 2, and 30 μg once in weeks 3 and 4 or Betaseron (interferon beta-1 b) every other day subcutaneously with 0.0625 mg in week 1, 0.125 mg in week two;
• 0.1875 mg in week 3;
• and 0.25 mg in week 4, plus tenofovir intravenously or intramuscularly at 5 mg to 150 mg twice daily for 1 day to 6 weeks or tenofovir disoproxil fumarate at about 150 mg twice daily for 1 day to 6 weeks;
• and
• (b) subsequently administering high-dose valomaciclovir stearate at about 1.5 g to 2 g twice daily combined with low-dose interferon type 1 (as described above) and low-dose tenofovir disoproxil fumarate orally once daily.

A method for treating relapsing-remitting multiple sclerosis or HLA marker DR2 (DRB1*1501) progressive multiple sclerosis, the method comprising the steps of:

• (a) administering H2G intravenously or intramuscularly at about 5 mg/kg to about 25 mg/kg twice daily for 1 day to 6 weeks or administering valomaciclovir stearate orally in combination with administering an additional agent selected from the group consisting of:
• (i) artesunate administered intravenously at about 2.4 mg/kg twice daily for 1 day to 6 weeks;
• (ii) ribavirin administered orally or by inhalation at about 100 mg to about 500 mg twice daily for 1 day to 6 weeks;
• and (iii) mycophenolate administered orally or intravenously at about 500 mg to about 1.5 mg twice daily for 1 day to 6 weeks;
• and
• (b) subsequently administering chronic low-dose valomaciclovir stearate at a dosage of about 1 g to about 2 g once daily.

A method for treating a disease or condition selected from the group consisting of acute infectious mononucleosis, chronic mononucleosis, long COVID, chronic fatigue syndrome, fibromyalgia, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, Alzheimer's disease, mesial temporal lobe seizures, Epstein-Barr-virus-linked autism, and an Epstein-Barr-virus-linked cancer, the method comprising the steps of:

• (a) administering H2G intravenously or intramuscularly at about 5 mg/kg to about 25 mg/kg twice daily or administering valomaciclovir stearate polymorph Form A orally at a high dose of about 1.5 g to 2 g orally twice daily in combination with administering an additional agent selected from the group consisting of:
• (i) artesunate administered intravenously at about 2.4 mg/kg twice daily for 1 day to 6 weeks;
• (ii) ribavirin administered orally or by inhalation at about 100 mg to about 500 mg twice daily for 1 day to 6 weeks;
• and (iii) mycophenolate administered orally or intravenously at about 500 mg to about 1.5 mg twice daily for 1 day to 6 weeks;
• (b) subsequently administering low-dose valomaciclovir stearate polymorph Form A at a dosage of about 1 g to 2 g once daily with chronic dosing;
• and
• (c) then subsequently administering a therapeutically effective quantity of an additional agent selected from the group consisting of an anti-CD20 agent, an anti-integrin α4β1 agent, and an anti-CD37 agent.

A method for treatment of glioblastoma comprising the steps of:

• (a) administering an induction agent selected from the group consisting of:
• (1) ribavirin administered at about 100 mg to about 400 mg twice daily for 1 day to 4 weeks;
• (2) romidepsin administered at about 14 mg/m2 on days 1 and 8;
• and
• (3) sodium phenylbutyrate administered at a loading dose of about 250 mg intravenously over 90 minutes, followed by a dose of about 250 mg/kg per day for 7 days;
• followed by
• (b) administering H2G intramuscularly or intravenously at a dose of about 5 mg/kg to about 25 mg/kg twice daily for 1 day to 6 weeks;
• followed by
• (c) administering artesunate at a dose of about 1 mg/kg to about 2.4 mg/kg for 1 day to 6 weeks;
• followed by
• (d) administering high dose polymorph Form A of valomaciclovir stearate at about 1.5 g to about 2 g twice daily for 1 week to 6 weeks, tenofovir disoproxil fumarate at about 75 mg twice daily for 1 day to 6 weeks, with the dose depending on the patient's renal function, and sildenafil at about 5 mg twice daily for 1 day to 6 weeks;
• and followed by
• (e) administering about 850 mg of polymorph Form A of valomaciclovir stearate twice daily, tenofovir disoproxil fumarate at about 75 mg twice daily, with the dose and dosing duration depending on the patient's renal function with chronic dosing, and sildenafil at about 5 mg to about 20 mg with twice daily chronic dosing.

A formulation of polymorph Form A of valomaciclovir stearate for oral administration, the formulation comprising, per unit dose:

• (a) 1000 mg of the Form A polymorph of valomaciclovir stearate;
• (b) 180.53 mg of croscarmellose sodium;
• (c) 42.31 mg of Povidone K-30;
• (d) 13.08 mg of polysorbate 80;
• (e) 53.21 mg of talc;
• and
• (f) 9.60 mg of magnesium stearate;
• wherein the formulation is in the form of caplets.

A method for triple therapy of long COVID comprising the steps of:

• (a) administering a therapeutically effective quantity of an induction agent for a human herpesvirus;
• (b) administering a therapeutically effective quantity of at least one antiviral agent selected from the group consisting of H2G and polymorph Form A of valomaciclovir stearate, wherein the antiviral agent or agents are administered in two stages:
• a first high-dose stage and a second low-dose chronic stage;
• and
• (c) administering a therapeutically effective quantity of an anti-B-cell agent selected from the group consisting of anti-CD20 agent, an anti-integrin α4β1 agent, or an anti-CD37 agent.

A capsule or tablet formulation comprising:

• (a) polymorph Form A of valomaciclovir stearate at about 500 mg to about 850 mg per capsule or tablet;
• (b) tenofovir disoproxil fumarate at about 75 mg per capsule or table (with daily dosing of tenofovir disoproxil fumarate dependent on the patient's renal status);
• and
• (c) pharmaceutical grade cod liver oil at about 80 mg to about 500 mg per capsule or tablet.

A capsule or tablet formulation comprising:

• (a) polymorph Form A of valomaciclovir stearate at about 500 mg to about 850 mg per capsule or tablet;
• (b) tenofovir disoproxil fumarate at about 75 mg per capsule or tablet (with daily dosing of tenofovir disoproxil fumarate dependent on the patient's renal status);
• and
• (c) sildenafil at about 5 mg to about 20 mg per capsule or tablet.

A method for treating long COVID cases in which both persistent SARS-CoV-2 virus and reactivated Epstein-Barr virus or reactivated HHV6 virus is of concern, the method comprising the steps of:

• (a) chronically administering a therapeutically effective quantity of nirmatrelvir;
• (b) chronically administering a therapeutically effective quantity of ritonavir;
• and
• (c) chronically administering a therapeutically effective quantity of polymorph Form A of valomaciclovir stearate.

A combination pill comprising:

• (a) about 75 mg of nirmatrelvir per unit dose;
• (b) about 50 mg of ritonavir per unit dose;
• and
• (c) about 750 mg of polymorph Form A of valomaciclovir stearate per unit dose.