US 2026/0263473 A1 · PRODUCTS OF MANUFACTURE AND THERAPEUTIC COMPOSITIONS FOR TREATING, AMELIORATING OR PREVENTING VIRAL INFECTIONS AND METHODS FOR MAKING AND USING THEM

Abstract

In alternative embodiments, provided are pharmaceutical compositions and therapeutic combinations of drugs, including products of manufacture and kits, for treating, preventing or ameliorating (for example, decreasing the symptoms of, or decreasing the mortality of) a viral infection, for example, a coronavirus infection such as a COVID-19 or variant thereof, and methods for making and using same. In alternative embodiments, provided are products of manufacture and kits for delivering pharmaceutical compositions and therapeutic combinations of drugs as provided herein, for example provided are transdermal delivery devices such as patches that can have multiple compartments for delivering transdermally different drugs at the same time.

A pharmaceutical composition or a therapeutic combination of drugs, comprising:

(a) (i) metformin (or GLUCOPHAGE™) and/or
(ii) a 3C-like (3CLpro) protease (also known as main protease (Mpro), also known as C30 endopeptidase or 3-chymotrypsin-like protease) inhibitor, optionally ensitrelvir (or XOCOVA™), or ensitrelvir fumaric acid,
wherein optionally the metformin is formulated or dosaged at between about 100 mg to mg per unit dosage (optionally, per tablet);
or the metformin is formulated or dosage at between about 0.1 ml to 25 ml liquid metformin/day;
and,
wherein optionally the ensitrelvir or ensitrelvir fumaric acid is formulated or dosaged at between about 100 mg to 500 mg per unit dosage, or at about 100 mg, 125 mg or 150 mg per unit dosage (optionally, per tablet);
and
(b) two of any of the following drugs or drug combinations if only metformin or the 3CLpro inhibitor are included, or one of (or at least one of) any of the following drugs or drug combinations if both metformin and 3CLpro are included:
(i) an avermectin class drug, or ivermectin (or STROMECTOL™);
(ii) an avermectin class drug, or ivermectin and an antibiotic (optionally doxycycline or azithromycin);
(iii) an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol, optionally with or without vitamin C;
(iv) an antibiotic;
(v) ivermectin;
and, an antibiotic (optionally doxycycline or azithromycin), at least one vitamin and zinc;
(vi) opaganib or YELIVA™;
(vii) opaganib and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(viii) plitidepsin (also known as dehydrodidemnin B), or APLIDIN™;
(ix) plitidepsin and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol, and optionally also vitamin D or cholecalciferol;
(x) lopinavir, ritonavir (or NORVIR™) and/or oseltamivir,
(xi) lopinavir, ritonavir and/or oseltamivir, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xii) nirmatrelvir and ritonavir (or PAXLOVID™),
(xiii) nirmatrelvir and ritonavir (or PAXLOVID™), and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xiv) chloroquine (optionally, ARALEN™), chloroquine phosphate, chloroquine diphosphate, hydroxychloroquine (optionally, PLAQUENIL™);
(xv) chloroquine, chloroquine phosphate, chloroquine diphosphate, hydroxychloroquine;
and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xvi) abacavir, acyclovir optionally, (ACICLOVIR™), adefovir, amantadine, ampligen, amprenavir (optionally, AGENERASE™), aprepitant, arbidol, atazanavir, atripla, balavir, baloxavir marboxil (XOFLUZA™), bepotastine, bevirimat, bictegravir, biktarvy, brilacidin, cidofovir, caspofungin, lamivudine and zidovudine (optionally, COMBVIR™), cobicstat, colisitin, cocaine, delavirdine, descovy, didanosine, docosanol, dolutegravir, ecoliever, edoxudine, elvitegravir, enfuvirtide, entecavir, epirubicin, epoprostenol, etravirine, famciclovir, fomivirsen, fosamprenavi, foscarnet, fosfonet, galidesivir, ibacitabine, icatibant, idoxuridine, ifenprodil, imiquimod, imunovir, indinavir, inosine, an interferon (optionally interferon type I, interferon type II and/or interferon type III), lamivudine, loviride, ledipasvir, leronlimab, maraviroc, methisazone, moroxydine, nexavir, norvir, a nucleoside analogue (optionally brincidofovir, didanosine, favipiravir (also known as T-705, avigan, or favilavir, Toyama Chemical, Fujifilm, Japan), vidarabine, galidesivir (optionally, BCX4430, IMMUCILLIN-A™), cytarabine, gemcitabine, lamivudine, zalcitabine, abacavir, acyclovir, entecavir, stavudine, telbivudine, zidovudine, idoxuridine and/or trifluridine or any combination thereof), oseltamivir (or TAMIFLU™), peginterferon alfa-2a, penciclovir, peramivir (optionally, RAPIVAB™), perfenazine, pleconaril, plurifloxacin, podophyllotoxin, pyramidine, raltegravir, rifampicin, rilpivirine, rimantadine, ritonavir, saquinavir, sofosbuvir, stavudine, telaprevir, tegobuv, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir (optionally, VALTREX™), valganciclovir, valrubicin, vapreotide, vicriviroc, vidarabine, viramidine, velpatasvir, vivecon, zalcitabine, zanamivir (optionally, RELENZA™), zidovudine, or any combination thereof;
(xvii) any one or more drug or drugs in (xiv);
and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xviii) molnupiravir, emtricitabine (or EMTRIVA™), efavirenz (or SUSTIVA™) or tenofovir;
or molnupiravir with emtricitabine and tenofovir (or ATRIPLA™);
(xix) molnupiravir, emtricitabine, efavirenz or tenofovir, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xx) zanamivir (or RELENZA™);
(xxi) zanamivir, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxii) efavirenz (optionally SUSTIVA™);
(xxiii) efavirenz, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxiv) nelfinavir (VIRACEPT™) or oseltamivir (or TAMIFLU™),
(xxv) nelfinavir (VIRACEPT™) or oseltamivir (or TAMIFLU™), and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxvi) a thiazolide class drug, optionally nitazoxanide (optionally ALINIA™, or NIZONIDE™) or tizoxanide (or 2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide);
(xxvii) a thiazolide class drug, optionally nitazoxanide, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxviii) remdesivir (optionally, GS-5734™, Gilead Sciences, or VEKLURY™);
(xxix) molnupiravir (or LAGEVRIO™);
(xxx) molnupiravir, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxi) nevirapine (or VIRAMUNE™);
(xxxii) nevirapine (or VIRAMUNE™), and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxiii) tenofovir alafenamide, tenofovir disoproxil or tenofovir;
(xxxiv) tenofovir alafenamide, tenofovir disoproxil or tenofovir, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxv) salamectin (or SELEHOLD™, REVOLT™, SELARID™ or SENERGY™);
(xxxvi) salamectin, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxvii) an inhibitor of an S-phase kinase-associated protein 2 (SKP2), or dioscin, or niclosamide, or NICLOCIDE™, FENASAL™, or PHENASAL™,
(xxxviii) an inhibitor of an S-phase kinase-associated protein 2 (SKP2), or dioscin, or niclosamide, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxix) ribavirin or tribavirin (or COPEGUS™, REBETOL™, or VIRAZOLE™);
(xxxx) ribavirin or tribavirin, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxi) a viral, or a coronavirus or a COVID-19, protease inhibitor, optionally ASC09 (CAS registry no. 1000287-05-7) (Janssen Research and Development, LLC), ritonavir or ASC09 and ritonavir, or a JAK1/2 inhibitor (optionally baricitinib), optionally compound 11r (University of Lubeck, Germany, see optionally, Zhang et al J. Med Chem 2020, Feb. 11, 2020), or darunavir (or PREZISTA™), cobicistat (or TYBOST™) or darunavir and cobicistat;
(xxxxii) a viral, or a coronavirus or a COVID-19, protease inhibitor, ritonavir, a JAK1/2 inhibitor (optionally baricitinib), or darunavir (or PREZISTA™) or cobicistat, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxiii) an mucolytic therapy or drug, optionally acetylcysteine, ambroxol, bromhexine, carbocisteine, erdosteine, mecysteine or dornase alfa, or an expectorant, optionally guaifenesin;
(xxxxiv) an mucolytic therapy or drug, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxv) an angiotensin-converting enzyme 2 (ACE2) inhibitor, optionally captopril, enalapril, lisinopril, benazepril, fosinopril, quinapril, ramipril, perindopril, moexipril or trandolapril;
(xxxxvi) an angiotensin-converting enzyme 2 (ACE2) inhibitor, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxvii) an anti-vascular endothelial growth factor (VEGF) (optionally VEGF-A) drug or antibody, optionally bevacizumab (or AVASTIN™);
(xxxxviii) an anti-vascular endothelial growth factor (VEGF) drug or antibody or bevacizumab and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxvix) a protease inhibitor, optionally danoprevir, optionally a serine protease inhibitor, optionally camostat (or FOIPAN™) or narlaprevir (optionally ARLANSA™)
(xxxxx) a protease inhibitor, danoprevir, a serine protease inhibitor, camostat or narlaprevir, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxi) anti-PD-1 checkpoint inhibitor, optionally camrelizumab, or a PD-1 inhibitor (or cemiplimab, dostarlimab, pembrolizumab or nivolumab) or a PD-L1 inhibitor (or atezolizumab, avelumab, cosibelimab or durvalumab);
(xxxxxii) anti-PD-1 checkpoint inhibitor, or camrelizumab, or a PD-1 inhibitor or a PD-L1 inhibitor, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxiii) thalidomide, or thalidomide and glucocorticoid (optionally low-dose glucocorticoid), or and thalidomide and celecoxib;
(xxxxxiv) thalidomide, or thalidomide and glucocorticoid (optionally low-dose glucocorticoid), and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxV) a compound or antibody capable of binding complement factor C5 and blocking membrane attack complex formation, or eculizumab;
(xxxxxvi) a compound or antibody capable of binding complement factor C5 and blocking membrane attack complex formation, or eculizumab, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxvii) a cathepsin inhibitor, optionally a cathepsin K, B or L inhibitor, or relacatib or balicatib;
(xxxxxviii) a cathepsin inhibitor, or relacatib or balicatib, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxix) a synthetic nucleoside analog or derivative, or N4-hydroxycytidine, or a prodrug of N4-hydroxycytidine, optionally molnuvpiravir (Merck), or favipiravir (also known as T-705 or AVIGAN™), or favilavir, Toyama Chemical, Fujifilm, Japan, or FABIFLU™ (Glenmark Pharmaceuticals), optionally dosaged at 800 mg bid;
(xxxxxx) a synthetic nucleoside analog or derivative, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol,
wherein the synthetic nucleoside analog or derivative, or N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine, optionally molnuvpiravir or favipiravir, is given as between about 10 mg to 3 gm per dose, or between about 10 mg to 3 gm per day, or can be dosed either as a single dose or given one, two, three or four times a day, or is administered at 200 to 800 mg twice daily, or 200, 400, 600 or 800 mg twice daily, or at 200 to 800 mg three times a day, or at 200, 400, 600 or 800 mg three times a day, or is administered at 200 to 800 mg three times a day for between about 2 to 15 days, or for about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 days, and optionally when combined with other drugs a lower dosage is used, optionally administered at 100 or 200 mg three times a day for between about 5 to 15 days, or for about 7, 8, 9, 10, 11 or 12 days;
(xxxxxxi) an anti-androgen drug, and optionally the anti-androgen drug is bicalutamide, or CASODEX™, or dutasteride (or AVODART™), and optionally the anti-androgen drug comprises a 5α-reductase inhibitor, and optionally the 5α-reductase inhibitor comprises finasteride (or PROSCAR™, PROPECIA™, or FINIDE™);
(xxxxxxii) an anti-androgen drug, and optionally the anti-androgen drug is bicalutamide, or CASODEX™, or dutasteride (or AVODART™), and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxiii) an anti-malarial drug, wherein optionally the anti-malarial drug comprises mefloquine (or LARIAM™, MEPHAQUIN™, or MEFLIAM™), wherein optionally the mefloquine is formulated for oral administration, optionally in tablet or capsule form, optionally as 200 mg, 250 mg or 300 mg tablets;
(xxxxxxiv) an anti-malarial drug, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxv) a peroxisome proliferator-activated receptor (PPAR) agonist, wherein optionally the PPAR agonist comprises fenofibrate, or TRICOR™, FENOBRAT™, FENOGLIDE™ or LIPOFEN™, optionally the PPAR agonist comprises a combination of fenofibrate and pravastatin, or PRAVAFENIX™, or the PPAR agonist comprises bezafibrate, or BEZALIP™, or combination of bezafibrate and chenodeoxycholic acid, or HEPACONDA™, or aluminium clofibrate, or alfibrate, or ciprofibrate, or clinofibrate or LIPOCLIN™, or clofibrate or ATROMID-S™, or clofibride, or gemfibrozil or LOPID™, or ronifibrate, or simfibrate or CHOLESOLVIN™, or any combination thereof,
(xxxxxxvi) a peroxisome proliferator-activated receptor (PPAR) agonist, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxvii) an acetaldehyde dehydrogenase inhibitor, optionally disulfiram, or ANTABUS™, or ANTABUSE™, optionally formulated as an extended, sustained or slow-release disulfiram formulation, optionally the extended, sustained or slow-release disulfiram is formulated as a tablet, a capsule or in an injectable, amphiphilic, absorbable, depot-forming drug delivery system (DDS),
(xxxxxxviii) an acetaldehyde dehydrogenase inhibitor, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxix) a nicotinic antagonist, a dopamine agonist or a noncompetitive N-Methyl-D-aspartate (NMDA) antagonist, optionally amantadine, or GOCOVRI™, or SYMADINE™, or SYMMETREL™, optionally dosaged at between about 100 to 200 mg per dose, optionally formulated as tablets or capsules,
(xxxxxxx) a nicotinic antagonist, a dopamine agonist or a noncompetitive N-Methyl-D-aspartate (NMDA) antagonist, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxi) a mitochondrial sensitizer, optionally proguanil or chlorguanide (or PALUDRINE™), or a malarial cytochrome bc1 complex inhibitor, optionally atovaquone (or MEPRON™), or a combination of proguanil and atovaquone (or MALARONE™),
and optionally the proguanil, atovaquone or the combination of proguanil and atovaquone are formulated for oral administration, optionally as tablets, optionally the unit dosage of atovaquone is 250 mg, 300 mg, 350 mg, 400 mg, 500 mg or 1 gram, and the unit dosage of proguanil is 100 mg, 250 mg, 300 mg, 350 mg or 400 mg;
(xxxxxxxii) a mitochondrial sensitizer or a malarial cytochrome bc1 complex inhibitor, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxiii) a dendrimer, optionally astodrimer sodium (Starpharma, Melbourne, Australia);
(xxxxxxxiv) a dendrimer, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxv) an antihistamine class drug, optionally azelastine, or ASTELIN™, OPTIVAR™, ALLERGODIL™, bepotastine (or TALION™, BEPREVE™), brompheniramine, fexofenadine or ALLEGRA™, pheniramine or AVIL™, or chlorpheniramine;
(xxxxxxxvi) an antihistamine class drug, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxvii) a selective serotonin reuptake inhibitor (SSRI) class drug, optionally fluvoxamine, or LUVOX™, FAVERIN™, FLUVOXIN™;
a peroxisome proliferator-activated receptor (PPAR) agonist, wherein optionally the PPAR agonist comprises fenofibrate, or TRICOR™, FENOBRAT™, FENOGLIDE™ or LIPOFEN™, optionally the PPAR agonist comprises a combination of fenofibrate and pravastatin, or PRAVAFENIX™, or the PPAR agonist comprises bezafibrate, or BEZALIP™, or combination of bezafibrate and chenodeoxycholic acid, or HEPACONDA™, or aluminium clofibrate, or alfibrate, or ciprofibrate, or clinofibrate or LIPOCLIN™, or clofibrate or ATROMID-S™, or clofibride, or gemfibrozil or LOPID™, or ronifibrate, or simfibrate or CHOLESOLVIN™, or any combination thereof;
(xxxxxxxviii) a selective serotonin reuptake inhibitor (SSRI) class drug, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxix) clofazimine, or LAMPENE™, optionally dosaged at about 100 mg per day, or between about 50 mg and 150 mg per day, and/or colchicine (or COLCRYS™, MITIGARE™), optionally dosaged at about 0.1 mg to 5 mg per day;
(xxxxxxxx) clofazimine or colchicine, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxxi) a selective estrogen receptor modulator (SERM), or toremifene (or FARESTON™), or clomifene or clomiphene (or CLOMID™, SEROPHENE™);
(xxxxxxxxii) a selective estrogen receptor modulator (SERM), or toremifene or clomifene or clomiphene, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxxiii) an alpha-ketoamide (a-ketoamide), wherein optionally the alpha-ketoamide is a structure as described by Zhang et al, J. Med. Chem. 2020, 63, 9, 4562-4578, or Meng et al Chem. Sci. (2019) vol. 10, pg 5156 (optionally the structure KAM-2);
(xxxxxxxxiv) an alpha-ketoamide, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxxv) an acylsulfonamide inhibitor of the NS3-4A serine protease, or paritaprevir, or ombitasvir, or paritaprevir and ombitasvir with ritonavir (TECHNIVIE™);
(xxxxxxxxvi) paritaprevir (or VERUPREVIR™), or ombitasvir, or paritaprevir and ombitasvir with ritonavir, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc, and optionally also vitamin D or cholecalciferol;
(xxxxxxxxvii) at least one vitamin, and optionally the at least one vitamin comprises:
vitamin B3 (or pyridine-3-carboxylic acid, niacin or nicotinic acid, or vitamin B3 or niacin administered as a slow release form (or NIASPAN FCT™), vitamin D (optionally D2, or ergocalciferol), or Vitamin D3 or cholecalciferol, optionally administered at about 1000 to 4000 ugm/day;
vitamin B12, vitamin B6 (or pyridoxine);
vitamin K;
vitamin A;
vitamin E;
and/or, vitamin C (optionally administered at 500 mg bid);
(xxxxxxxxviii) at least one vitamin, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc;
(xxxxxxxxix) a compound, drug or formulation that decreases stomach acid production or decreases stomach pH, wherein optionally the compound, drug or formulation comprises famotidine, or PEPCID™, and optionally the famotidine is administered at a dosage of between about 10 to 60 mg per day, or between about 20 to 40 mg per day;
(xxxxxxxxx) famotidine, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc;
(xxxxxxxxxi) an immunosuppressive drug, wherein optionally the immunosuppressive drug comprises tocilizumab or atlizumab, or ACTEMRA™, or ROACTEMRA™, or a calcineurin inhibitor (CNI), wherein the CNI comprises ciclosporin (or cyclosporine or cyclosporin), or NEORAL™, or SANDIMMUNE™, or tacrolimus, or PROTOPIC™, or PROGRAF™.
(xxxxxxxxxii) an immunosuppressive drug or a calcineurin inhibitor, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc;
(xxxxxxxxxiii) an anti-inflammatory therapy or at least one anti-inflammatory therapy drug, wherein optionally the anti-inflammatory therapy or drug comprises:
a sphingosine kinase-2 (SK2) selective inhibitor (optionally, opaganib (optionally, YELIVA™), sirolimus, a JAK1/2/TYK2 inhibitor (optionally ruxolitinib), an anti-CD47 mAb (optionally meplazumab), a cyclooxygenase (COX) (optionally, COX2) inhibitor, a glucocorticoid (optionally a synthetic glucocorticoid, hydrocortisone, dexamethasone (or DEXTENZA™, OZURDEX™, or NEOFORDEX™) or cortisol, or CORTEF™), plitidepsin or dehydrodidemnin B, or APLIDIN™;
and/or
(xxxxxxxxxiv) an anti-inflammatory therapy or at least one anti-inflammatory therapy drug, and:
an avermectin class drug, or ivermectin;
an antibiotic (optionally doxycycline or azithromycin), and zinc;
wherein optionally the avermectin class drug comprises:
ivermectin (or STROMECTOL™), moxidectin (or CYDECTIN™, EQUEST™, QUEST™), selamectin (or STRONGHOLD™), a milbemycin (optionally milbemectin, milbemycin oxime, moxidectin or nemadectin), doramectin (or DECTOMAX™), eprinomectin or abamectin, and optionally the avermectin class drug or ivermectin is dosaged for administration at between about 50 to 2000 μgm/kg body weight per day, optionally dosaged at 200 μgm/kg per day, or about 14 mg/day, optionally dosaged at 220, 225, 150, 275 or 300 μgm/kg per day, or optionally dosaged at 12, 14, 16, 18, 20, 22, 24 or 26 mg per day, or optionally dosaged at between about 10 to 30 mg per day,
and optionally the avermectin class drug or ivermectin is dosaged for administration at between about 5 to 480 or between about 3 to 500 mg per day,
and optionally the avermectin class drug (optionally ivermectin) is formulated or dosaged at between about 15 to 150 mg/kg, or is about 18, 24, 30, 35, 40, 35, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110 or 120 or more mg/kg,
and optionally the antibiotic comprises a tetracycline class drug, and optionally the tetracycline class drug comprises tetracycline, doxycycline, chlortetracycline, oxytetracycline, glycylcycline, fluorocycline or demeclocycline, tetracycline or SUMYCIN™;
chlortetracycline or AUREOMYCIN™;
oxytetracycline;
demeclocycline or DECLOMYCIN™ DECLOSTATIN™, LEDERMYCIN™, BIOTERCICLIN™, DEGANOL™, DETECLO™, DETRAVIS™, MECICLIN™, MEXOCINE™, CLORTETRIN™;
lymecycline;
meclocycline;
metacycline;
minocycline or MINOCIN™;
rolitetracycline;
doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™;
tigecycline or TYGACIL™;
eravacycline or XERAVA™;
sarecycline or SEYSARA™;
omadacycline or NUZYRA™;
or any combination thereof,
and optionally the therapeutic combination comprises about 25 mg to about 600 mg of the tetracycline class drug, or tetracycline, doxycycline, chlortetracycline, oxytetracycline or demeclocycline,
and optionally the antibiotic comprises a macrolide drug, and optionally the macrolide drug comprises azithromycin, optionally dosaged at between about 50 mg to about 2000 mg per dose or per day (optionally, ZITHROMAX™, or AZITHROCIN™, optionally an oral extended- or delayed-release formulation of azithromycin, or ZMAX™), clarithromycin (optionally, BIAXIN™), erythromycin (optionally, ERYTHROCIN™), or fidaxomicin (optionally, DIFICID™ or DIFICLIR™), troleandomycin (optionally, TEKMISIN™), tylosin (optionally, TYLOCINE™ or TYLAN™), solithromycin (optionally, SOLITHERA™), oleandomycin (or SIGMAMYCINE™), midecamycin, roxithromycin, kitasamycin or turimycin, josamycin, carbomycin or magnamycin, and/or spiramycin,
and optionally the antibiotic comprises azithromycin, and optionally the therapeutic combination comprises between about 50 mg to about 2000 mg azithromycin, or optionally the azithromycin comprises an oral extended-release formulation of azithromycin,
and optionally the antibiotic comprises a nitroimidazole, or a 2-, 4- and/or 5-nitroimidazole, or a 5-nitro nitroimidazole comprising metronidazole, tinidazole, nimorazole, dimetridazole, pretomanid, ornidazole, megazol and/or azanidazole, or a 2-nitromidazoles comprising benznidazole,
and optionally the antibiotic comprises a-lactam antibiotic such as penicillin class drug or a cephalosporin class drug,
and optionally the cephalosporin class drug comprises cefalexin or cephalexin, cefadroxil or cefadroxyl, cefazolin or cephazolin, cefapirin or cephapirin, cefalotin or cephalothn, cefradine or corcephradine, cefprozil or cefproxil, cefuroxime, ceftolozane, cefonicid or cefaclor,
and optionally the penicillin class drug comprises penicillin V, penicillin G, cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin, oxacillin, ampicillin, amoxicillin, pivampicillin, bacampicillin, metampicillin, talampicillin, hetacillin, carbenicillin, ticarcillin, temocillin, mezlocillin, piperacillin, azlocillin, clavulanic acid, sulbactam or tazobactam,
and optionally the antibiotic comprises a quinolone class antibiotic such as a fluoroquinolone, or comprises ciprofloxacin, garenoxacin, gatifloxacin, gemifloxacin, levofloxacin or moxifloxacin,
and optionally the antibiotic comprises an ansamycin class drug, or rifampicin, also known as rifampin, bedaquiline,
and optionally the antibiotic comprises artemisinin, amodiaquine, proguanil, sulfadoxine, sulfamethoxypyridazine, pyrimethamine, linezolid, quinine, quinidine, cinchonine, cinchonidine (or quinimax), hydroxychloroquine or chloroquine,
and optionally the at least one vitamin comprises vitamin D or cholecalciferol, or vitamin C, or vitamin D or cholecalciferol and vitamin C, and vitamin D or cholecalciferol is dosaged at between about 3,000 to about 100,000 units vitamin D or cholecalciferol, and optionally the therapeutic combination comprises between about 10,000 to about 50,000 units vitamin D or cholecalciferol, and optionally the vitamin comprises vitamin C, and optionally the vitamin C is formulated or administered at a dosage of between about 500 to 5000 units (U) per dose,
and optionally the zinc comprises or is formulated as:
a zinc salt, a zinc chelate, a zinc sulphate, a zinc acetate, a zinc gluconate or a zinc picolinate, and optionally the therapeutic combination comprises between about 1 mg to 250 mg zinc, zinc sulphate, zinc acetate, zinc gluconate or zinc picolinate, or zinc oxide nanoparticles, optionally at a dosage of between about 1 mg to 250 mg,
and optionally the pharmaceutical composition or a therapeutic combination further comprises copper, optionally administered or formulated at a dosage of between about 1 to 200 mg per day, wherein optionally the copper is administered or formulated as cupric chloride and administered intravenously formulated at about 0.4 mg/ml;
and optionally the pharmaceutical composition or a therapeutic combination further comprises selenium, optionally administered as selenious acid formulated at about 65.4 mcg/ml (or μ/ml), and optionally the selenium is administered at a dosage of between about 50 to 100 μ/ml, optionally between about 60 to 100 μgm per day is administered to an adult, and only up to 60 μgm per day for pediatric patients.

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Products of manufacture and therapeutic compositions for treating, ameliorating or preventing viral infections and methods for making and using them

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Products of manufacture and therapeutic compositions for treating, ameliorating or preventing viral infections and methods for making and using them

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Abstract

Claims22