Nuclease-dendrimer formulations for covid-19 and broad-spectrum antiviral therapy and prophylaxis

Abstract

Compositions of nucleases in formulations with dendrimers are used in pharmaceutically effective dosages as therapeutics for covid-19 and a broad spectrum of viruses in various embodiments. When cationized nucleases are mixed and/or complexed with a dendrimer, an unexpected positive dendrimer effect is manifest. This positive dendrimer effect is shown to be highly effective for catalyzing anti-viral RNase properties. In various embodiments compositions of cationized nucleases in combination with a dendrimer demonstrated this synergistic amplification of anti-viral effectiveness and are used in pharmaceutically effective dosages as therapeutics against covid-19 and a broad spectrum of viruses. An exemplar formulation which exhibits a positive dendrimer effect is cationized RNase A mixed and/or complexed with gen 2 PAMAM dendrimer.

We claim: 
     
         1 . A method for treating a mammal infected by a virus, comprising:
 administering a therapeutically effective amount of a pharmaceutical composition to the mammal, wherein the pharmaceutical composition comprises a nuclease mixed or complexed with a dendrimer;   wherein the nuclease and the dendrimer are selected such that the pharmaceutical composition's antiviral effectiveness exceeds an additive antiviral effectiveness of an antiviral effectiveness of the nuclease and an antiviral effectiveness of the dendrimer.   
     
     
         2 . The method of  claim 1  wherein the nuclease is a cationized nuclease. 
     
     
         3 . The method of  claim 1  wherein the cationized nuclease is cationized RNase A. 
     
     
         4 . The method of  claim 3  wherein the cationized RNase A is chosen from the group consisting of: RNase A-SO 3   − , RNaseA-OH, and RNaseA-NH 3   + . 
     
     
         5 . The method of  claim 1  wherein the virus is a coronavirus. 
     
     
         6 . The method of  claim 5  where the coronavirus is SARS-2-Cov or covid-19. 
     
     
         7 . The method of  claim 1  wherein the dendrimer is chosen from the group of: generation 1 poly PAMAM dendrimer, generation 2 poly PAMAM dendrimer, generation 3 poly PAMAM dendrimer, generation 4 poly PAMAM dendrimer, generation 5 poly PAMAM dendrimer, generation 6 poly PAMAM dendrimer, generation 7 poly PAMAM dendrimer, generation 8 poly PAMAM dendrimer, generation 9 poly PAMAM dendrimer. 
     
     
         8 . The method of  claim 1  wherein a therapeutic concentration of the dendrimer is at least 3 μM and less than 30 μM. 
     
     
         9 . The method of  claim 2  wherein a therapeutic concentration of the catioized nuclease is at least 5 μg/ml and less than 30 μg/ml. 
     
     
         10 . The method of  claim 5  wherein the coronavirus HCoV-OC43. 
     
     
         11 . A composition for treatment of a viral infection comprising a therapeutically effective formulation of at least one nuclease and at least one dendrimer. 
     
     
         12 . The composition of  claim 11  wherein the nuclease is a cationized nuclease. 
     
     
         13 . The composition of  claim 11  wherein the at least one nuclease comprises cationized RNase A. 
     
     
         14 . The composition of  claim 13  wherein the cationized RNase A is chosen from the group of:
 RNase A-SO 3   − , RNaseA-OH, and RNaseA-NH 3   + . 
 
     
     
         15 . The composition of  claim 11  wherein the viral infection is a coronavirus. 
     
     
         16 . The composition of  claim 15  where the coronavirus is covid-19. 
     
     
         17 . The composition of  claim 12  wherein the cationized nuclease's base nuclease is chosen from the group consisting of: RNase 1, RNase A, RNase H, RNase III, RNase L, RNase P, RNase PhyM, RNase T1, RNase T2, RNase U2, RNase V, RNase E, RNase G, PNPase, RNase PH, RNase R, RNase D, RNase T, Oligoribonuclease, Exoribonuclease I, Exoribonuclease II. 
     
     
         18 . The composition of  claim 11  wherein the at least one dendrimer comprises a generation 2 poly PAMAM dendrimer. 
     
     
         19 . The composition of  claim 11  wherein the at least one dendrimer is chosen from the group consisting of: generation 1 poly PAMAM dendrimer, generation 2 poly PAMAM dendrimer, generation 3 poly PAMAM dendrimer, generation 4 poly PAMAM dendrimer, generation 5 poly PAMAM dendrimer, generation 6 poly PAMAM dendrimer, generation 7 poly PAMAM dendrimer, generation 8 poly PAMAM dendrimer, generation 9 poly PAMAM dendrimer. 
     
     
         20 . The composition of  claim 11  wherein a therapeutic concentration of the at least one dendrimer is at least 3 μM and less than 30 μM. 
     
     
         21 . The composition of  claim 11  wherein a therapeutic concentration of the nuclease is at least 5 μg/ml and less than 30 μg/ml. 
     
     
         22 . The composition of  claim 15  wherein the coronavirus HCoV-OC43. 
     
     
         23 . A use of a composition comprising a nuclease and a dendrimer for the manufacture of a medicament for the treatment of human coronavirus. 
     
     
         24 . The use of the composition of  claim 21  wherein the nuclease is cationized RNase. 
     
     
         25 . The use of the composition of  claim 21  wherein the dendrimer is a generation 2 PAMAM dendrimer.