Methods and compositions related to inhibition of viral entry

Abstract

Disclosed herein are compositions and methods for inhibiting viral entry.

1 . A composition comprising at least one D-peptide linked to a potency-enhancing cargo with a polyethylene glycol (PEG) linker. 
     
     
         2 . The composition of  claim 1 , wherein the at least one D-peptide is capable of binding with a N-trimer pocket of a viral transmembrane protein. 
     
     
         3 . The composition of  claim 1 , wherein the PEG linker comprises at least 12 ethylene glycol repeats and links the at least one D-peptide to the potency-enhancing cargo. 
     
     
         4 . The composition of  claim 1 , wherein the PEG linker is one of PEG 12 , PEG 16 , PEG 24 , PEG 25 , PEG 26 , PEG 27 , PEG 28 , PEG 29 , PEG 30 , PEG 31 , PEG 32 , PEG 33 , PEG 34 , PEG 35 , or PEG 36 . 
     
     
         5 . The composition of  claim 1 , wherein the potency-enhancing cargo is at least one of a sterol, albumin, polyethylene glycol, a sugar, maltose binding protein, serum albumin, cholesterol, ubiquitin, Streptavidin, immunoglobulin domains, keyhole limpet hemacyanin, sperm whale myoovalbumin, bovine pancreatic trypsin inhibitor, Green Fluorescent Protein, gold particles, magnetic particles, agarose beads, lactose beads, or fatty acid. 
     
     
         6 . The composition of  claim 1 , wherein the potency-enhancing cargo is a cholesterol or an analog thereof. 
     
     
         7 . The composition of  claim 1 , wherein the potency-enhancing cargo is a fatty acid. 
     
     
         8 . The composition of  claim 7 , wherein the fatty acid is at least of a C8 fatty acid, a C16 fatty acid, and a C18 fatty acid. 
     
     
         9 . The composition of  claim 1 , wherein the potency-enhancing cargo is an alkane chain. 
     
     
         10 . The composition of  claim 9 , wherein the alkane is at least one of a C6 alkane, C16 alkane, and a C18 alkane. 
     
     
         11 . The composition of  claim 1 , wherein the at least one D-peptide is at least one of SEQ ID NOS: 1-29. 
     
     
         12 . The composition of  claim 1 , wherein the at least one D-peptide comprises at least one of PIE7 and PIE12. 
     
     
         13 . The composition of  claim 1  consisting of chol-PEG 24 -PIE12. 
     
     
         14 . A composition comprising at least three D-peptides linked to a multimer scaffold, wherein the at least three D-peptides are linked to the multimer scaffold with a polyethylene glycol (PEG) linker. 
     
     
         15 . The composition of  claim 14 , wherein the at least three D-peptides are capable of biding with a N-trimer pocket of a viral transmembrane protein. 
     
     
         16 . The composition of  claim 14 , wherein the PEG linker comprises at least 2 ethylene glycol repeats. 
     
     
         17 . The composition of  claim 14 , wherein the PEG linker is one of PEG 4  or PEG 5 . 
     
     
         18 . The composition of  claim 14 , wherein the multimer scaffold is a trimeric scaffold comprising three NHS ester groups. 
     
     
         19 . The composition of  claim 18 , wherein the at least three D-peptides are linked to the trimeric scaffold by the NHS ester groups. 
     
     
         20 . The composition of  claim 14 , wherein the multimer scaffold comprises a tris, di-lysine, benzene ring, phosphate, or peptide core. 
     
     
         21 . The composition of  claim 14 , wherein the at least three D-peptides are the same D-peptides. 
     
     
         22 . The composition of  claim 14 , wherein the at least three D-peptides comprise at least two different D-peptides. 
     
     
         23 . The composition of  claim 14 , wherein the at least three D-peptides comprise at least one of SEQ ID NOS: 1-29. 
     
     
         24 . The composition of  claim 14 , wherein the at least three D-peptides comprise at least one of PIE7 and PIE12. 
     
     
         25 . The composition of  claim 14  consisting of PEG 4 -PIE12-trimer. 
     
     
         26 . A composition comprising at least three D-peptides and at least one potency-enhancing cargo linked to a multimer scaffold. 
     
     
         27 . The composition of  claim 26 , wherein the multimer scaffold is a heterotetrameric scaffold comprising three NHS ester groups and a fourth orthogonal group. 
     
     
         28 . The composition of  claim 27 , wherein the at least three D-peptides are linked to the heterotetrameric scaffold via the three NHS ester groups and the at least one potency-enhancing group is linked to the heterotetrameric scaffold via the fourth orthogonal group. 
     
     
         29 . The composition of  claim 28 , wherein the at least one potency-enhancing group is linked to the heterotetrameric scaffold via the fourth orthogonal group with a polyethylene glycol (PEG) linker. 
     
     
         30 . The composition of  claim 29 , wherein the PEG linker comprises at least 12 ethylene glycol repeats. 
     
     
         31 . The composition of  claim 29 , wherein the PEG linker is one of PEG 12 , PEG 16 , PEG 24 , PEG 25 , PEG 26 , PEG 27 , PEG 28 , PEG 29 , PEG 30 , PEG 31 , PEG 32 , PEG 33 , PEG 34 , PEG 35 , PEG 36 , PEG 57 , or PEG 132 . 
     
     
         32 . The composition of  claim 26 , wherein the multimer scaffold comprises a tris, di-lysine, benzene ring, phosphate, or peptide core. 
     
     
         33 . The composition of  claim 26 , wherein the potency-enhancing group is linked to the heterotetrameric scaffold via a maleimide reactive group. 
     
     
         34 . The composition of  claim 26 , wherein the potency-enhancing cargo is at least one of a sterol, albumin, polyethylene glycol, a sugar, maltose binding protein, serum albumin, cholesterol, ubiquitin, Streptavidin, immunoglobulin domains, keyhole limpet hemacyanin, sperm whale myoovalbumin, bovine pancreatic trypsin inhibitor, Green Fluorescent Protein, gold particles, magnetic particles, agarose beads, lactose beads, or fatty acid. 
     
     
         35 . The composition of  claim 26 , wherein the potency-enhancing cargo is a cholesterol or an analog thereof. 
     
     
         36 . The composition of  claim 26 , wherein the potency-enhancing cargo is a fatty acid. 
     
     
         37 . The composition of  claim 36 , wherein the fatty acid is at least of a C8 fatty acid, a C16 fatty acid, and a C18 fatty acid. 
     
     
         38 . The composition of  claim 26 , wherein the potency-enhancing cargo is an alkane chain. 
     
     
         39 . The composition of  claim 38 , wherein the alkane chain is at least one of a C6 alkane, C16 alkane, and a C18 alkane. 
     
     
         40 . The composition of  claim 26 , wherein the at least three D-peptides are at least one of SEQ ID NOS: 1-29. 
     
     
         41 . The composition of  claim 26 , wherein the at least three D-peptides comprise at least one of PIE7 and PIE12. 
     
     
         42 . The composition of  claim 26  consisting of at least one of chol-PEG 12 -PIE12-trimer, chol-PEG 16 -PIE12-trimer, chol-PEG 24 -PIE12-trimer, chol-PEG 36 -PIE12-trimer, chol-PEG 57 -PIE12-trimer, chol-PEG 132 -PIE12-trimer, C8 fatty acid-PEG 24 -PIE12-trimer, C16 fatty acid-PEG 24 -PIE12-trimer, C18 fatty acid-PEG 24 -PIE12-trimer, C8 alkane-PEG 24 -PIE12-trimer, C16 alkane-PEG 24 -PIE12-trimer, and C18 alkane-PEG 24 -PIE12-trimer. 
     
     
         43 . The composition of  claim 1 , wherein the composition inhibits viral entry into a cell. 
     
     
         44 . A pharmaceutical composition comprising the composition of  claim 1 . 
     
     
         45 . A method for inhibiting viral entry into a cell comprising exposing the virus to the composition of  claim 1 , thereby inhibiting viral entry into a cell. 
     
     
         46 . The method of  claim 45 , wherein the virus is HIV. 
     
     
         47 . A method of treating a viral infection in a subject comprising administering to the subject an effective amount of the composition of  claim 1 . 
     
     
         48 . The method of  claim 47 , wherein the virus is HIV. 
     
     
         49 . The method of  claim 47 , further comprising administering to the subject an antiviral agent or agents selected from the group consisting of a viral replication inhibitor, a viral protease inhibitor, a viral reverse transcriptase inhibitor, a viral entry inhibitor, a viral integrase inhibitor, a viral Rev inhibitor, a viral Tat inhibitor, a viral Nef inhibitor, a viral Vpr inhibitor, a viral Vpu inhibitor, and a viral Vif inhibitor. 
     
     
         50 . The composition of  claim 14 , wherein the composition inhibits viral entry into a cell. 
     
     
         51 . The composition of  claim 26 , wherein the composition inhibits viral entry into a cell. 
     
     
         52 . A pharmaceutical composition comprising the composition of  claim 14 . 
     
     
         53 . A pharmaceutical composition comprising the composition of  claim 26 . 
     
     
         54 . A method for inhibiting viral entry into a cell comprising exposing the virus to the composition of  claim 14 , thereby inhibiting viral entry into a cell. 
     
     
         55 . A method for inhibiting viral entry into a cell comprising exposing the virus to the composition of  claim 26 , thereby inhibiting viral entry into a cell. 
     
     
         56 . A method of treating a viral infection in a subject comprising administering to the subject an effective amount of the composition of  claim 14 . 
     
     
         57 . A method of treating a viral infection in a subject comprising administering to the subject an effective amount of the composition of  claim 26 .