FORMULATION, USE AND METHOD FOR BROAD-SPECTRUM PROPHYLAXIS AND TREATMENT OF VIRAL INFECTIONS CAUSED BY SARS-CoV-2 AND OTHER EMERGING VIRUSES

Abstract

EGCG-Zn 2+ molecular complexes exhibit a significantly higher affinity than the EGCG molecule alone or Zn 2+ molecule alone for binding to different SARS-CoV-2 molecular targets and show virtually complete antiviral suppressive activity (>99%) against this virus in experimental models of infection. EGCG-Zn 2+ complexes have a lower toxicity than EGCG alone in transfected human cells. The combination of EGCG and Zn 2+ , significantly improved some key pharmacokinetic parameters of EGCG in humans. Thus, these complexes are usable as a new broad-spectrum method for chemoprophylaxis or treatment of viral diseases by using formulations containing a composition of EGCG and Zn 2+ or EGCG-Zn 2+ complexes in sufficient amount to reach a blood concentration with antiviral effect, minimizing human safety issues.

1 . EGCG-Zn 2+  complexes with a high suppressive synergistic activity and low toxicity for the prevention and treatment of enveloped viruses infections, including SARS-CoV-2, being said EGCG-Zn 2+  complexes represented by the formulae: 
       
         
           
           
               
               
           
         
       
       wherein these 3 complexes conformations were modeled in proportions EGCG-Zn 2+  of 1:1, 1:2 and 2:1. 
     
     
         2 . The complexes of  claim 1 , wherein the infection is produced by SARS-CoV-2 virus. 
     
     
         3 . The complexes of  claim 1  for the treatment of coronavirus disease 2019 (COVID-19) by inhibiting viral reproduction in the host by binding of the compound to the ATPase site of NCP15 of the SARS-CoV-2. 
     
     
         4 . The complexes of  claim 1  for the prevention and treatment of COVID-19 by inhibiting viral reproduction in the host by deactivating the PLP complex of the SARS-CoV-2. 
     
     
         5 . The complexes of  claim 1  for the prevention and treatment of COVID-19 by inhibiting the interaction between the Spike protein of SARS-CoV 2 with the host ACE2 receptor of the SARS-CoV-2. 
     
     
         6 . The complexes of  claim 1  for the prevention and treatment of COVID-19 by interacting with the 3CLpro protein of the SARS-CoV 2. 
     
     
         7 . The complexes of  claim 1  for the prevention and treatment of COVID-19 by interacting with the RdRp protein of the SARS-CoV-2. 
     
     
         8 . An antiviral formulation containing any of the EGCG-Zn 2+  complexes of  claim 1 , where the source of Zn 2+  can be a salt of zinc, consisting of zinc sulfate, zinc gluconate, zinc iodide, zinc chloride, zinc citrate, zinc carbonate, zinc hydroxide, zinc lactate, zinc acetate, zinc fluoride, zinc bromide, zinc sulfonate, zinc glucuronate, and zinc picolinate. 
     
     
         9 . The antiviral formulation of  claim 8  wherein it is in the form of an oral dosage. 
     
     
         10 . A method for treating a patient against infectious diseases caused by at least one virus, comprising the step of providing to the patient in need thereof a formulation containing the complexes according to  claim 1 , in a sufficient quantity for a sufficient period of time. 
     
     
         11 . The method of  claim 10 , comprising the step of providing at least once a day to a human or animal in need thereof, a formulation containing a combination of at least 10 mg up to 1000 mg of EGCG and at least 1 mg up to 30 mg of Zn in the form of EGCG-Zn 2+  complexes, during a time at least between 1-30 days, when the individual is considered healthy, wherein the antiviral effect and efficacy of EGCG and/or Zn is enhanced. 
     
     
         12 . The method of  claim 10 , wherein the infectious disease is caused in humans by an enveloped virus and is prevented and treated by providing at least once a day to an individual in need thereof, a formulation containing a combination of at least 10 mg up to 1000 mg of EGCG and at least 1 mg up to 30 mg of Zn in the form of EGCG-Zn 2+  complexes, during a time at least between 1-30 days when the individual is considered to be out of risk of infection or healthy. 
     
     
         13 . The method of  claim 10 , wherein the bioavailability of EGCG for clinical use is improved by providing at least once a day to a human or animal in need thereof, a formulation containing a combination of at least 10 mg up to 1000 mg of EGCG and at least 1 mg up to 30 mg of Zn in the form of EGCG-Zn 2+  complexes, during a time at least between 1-30 days. 
     
     
         14 . The method of  claim 10 , wherein immunologic complications from an infectious disease caused in humans by an enveloped virus is prevented and treated by providing at least once a day to an individual in need thereof, a formulation containing a combination of at least 10 mg up to 1000 mg of EGCG and at least 1 mg up to 30 mg of Zn in the form of EGCG-Zn 2+  complexes, during a time at least between 1-30 days when the individual is considered to be out of risk of immunologic complications or healthy. 
     
     
         15 . The method of  claim 10 , wherein toxicity is decreased, tolerability is increased and safety issues are minimized with the clinical use of EGCG when providing at least once a day to an individual in need thereof, a formulation containing a combination of at least 10 mg up to 1000 mg of EGCG and at least 1 mg up to 30 mg of Zn in the form of EGCG-Zn 2+  complexes, during a time at least between 1-30 days. 
     
     
         16 . The method of  claim 10 , wherein the formulation is administered in sufficient quantity for the pre- and post-exposure prophylaxis of a disease caused in humans by emergent viruses, including SARS-CoV-2. 
     
     
         17 . The method of  claim 10 , wherein the formulation is administered in sufficient quantity for the early treatment of a disease caused in humans by enveloped viruses, including SARS-CoV-2. 
     
     
         18 . The method of  claim 10 , wherein the formulation is administered in sufficient quantity to alleviate and shorten symptoms caused in humans by enveloped viruses, including SARS-CoV-2. 
     
     
         19 . The method of  claim 10 , wherein the formulation is administered as a complement or adjuvant to standard therapies used for the treatment of diseases caused in humans by enveloped viruses, including SARS-CoV-2. 
     
     
         20 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the viral translation in experiments involving enveloped viruses, including SARS-CoV-2. 
     
     
         21 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the viral adsorption in experiments involving enveloped viruses, including SARS-CoV-2. 
     
     
         22 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the viral absorption in experiments involving enveloped viruses, including SARS-CoV-2. 
     
     
         23 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the viral replication in experiments involving enveloped viruses, including SARS-CoV-2. 
     
     
         24 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the Papain-Like-Protein (PLP) of SARS-CoVs. 
     
     
         25 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the main protease 3CLpro of SARS-CoVs. 
     
     
         26 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the RNA dependent RNA polymerase (RdRp) of SARS-CoVs. 
     
     
         27 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the Spike Protein (S) of SARS-CoVs. 
     
     
         28 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the NSP15 of SARS-CoV-2 by interfering or blocking its active domain. 
     
     
         29 . The method of  claim 10 , wherein the formulation is administered as an immunomodulatory medication to treat an infection with an emergent enveloped virus, including SARS-CoV-2. 
     
     
         30 . The method of  claim 10 , wherein the formulation is administered as inhibitor of the domain RBD-ACE2 by interfering or blocking the viral adsorption of SARS-CoV-2. 
     
     
         31 . The method of  claim 10 , wherein the formulation is administered orally, intravenously, intramuscularly, endonasal, and subcutaneously for the treatment of a disease caused in humans by enveloped viruses, including SARS-CoV-2. 
     
     
         32 . The method of  claim 10 , wherein the formulation is administered as aerosol or nebulization for the treatment of a disease caused in humans by enveloped viruses, including SARS-CoV-2. 
     
     
         33 . The method of  claim 10 , wherein the formulation is administered for inhibiting the Papain-Like-Protein (PLP) of SARS-CoVs by interacting with the amino acids ASN-109A, GLY-160A, GLU-161A, LEU-162A, GLN-269A, GLN-160B, GLU-161B, LEU-162B, GLN-269B, HIS-89C, ASP-108C, ASN-109C, VAL-159C, GLY-160C, and GLN-269C. 
     
     
         34 . The method of  claim 10 , wherein the formulation is administered for inhibiting the main protease 3CLpro of SARS-CoVs by interacting with the amino acids THR-26, LEU-27, HIS-41, MET-49, TYR-54, PHE-140, LEU-141, ASN-142, CYS-145, HIS-164, MET-165, GLU-166, ASP-187, ARG-188, and GLN-189. 
     
     
         35 . The method of  claim 10 , wherein the formulation is administered for inhibiting the RNA dependent RNA polymerase (RpRd) of SARS-CoVs by interacting with the amino acids LEU-270, PRO-323, THR-324, PHE-326, PHE-396, and VAL-675. 
     
     
         36 . The method of  claim 10 , wherein the formulation is administered for inhibiting the Spike Protein (S) of SARS-CoVs by interacting with the amino acids LEU-546A, THR-547A, ASP-568A, THR-572A, THR-573A, PRO-589A, MET-740B, TYR-741B, ILE-742B, CYS-743B, GLY-744B, ASP-745B, PHE-855B, ASN-856B, VAL-976B, ASN-978B, and ARG-1000B 
     
     
         37 . The method of  claim 10 , wherein the formulation is administered for inhibiting the NSP15 of SARS-CoV-2 by interfering or blocking its active domain made up of amino acids HIS-235, GLY-248, HIS-250, LYS-290, CYS-291, VAL-292, SER-294, TRP-333, THR-341, TYR-343, PRO-344, LYS-345, and LEU-346 
     
     
         38 . The method of  claim 10 , wherein the formulation is administered for inhibiting the NSP15 of SARS-CoV-2 by interfering or blocking the amino acids LYS-71, LYS-90, THR-167, THR-196, GLN-197, SER-198, ARG-199, ASN-200, LEU-252, ASP-273, SER-274, THR-275, LYS-277, TYR-279, VAL-295, ILE-296, and ASP-297. 
     
     
         39 . The method of  claim 10 , wherein the formulation is administered for inhibiting the domain RBD-ACE2 by interacting with the amino acids ILE-291, MET-366, ASP-367, LEU-370, THR-371, HIS-374, GLU-406, SER-409, LEU-410, PHE-438, GLN-442, and ILE-446.