Bifunctional molecules for inactivating HIV and blocking HIV entry
Disclosed herein are bifunctional molecules which inactivate human immunodeficiency virus (HIV) even before the virus attacks the target cell and inhibits HIV entry into the target cell. Also disclosed are novel anti-HIV therapeutics for treatment of patients infected by HIV. Further disclosed are methods for prophylaxis against HIV and treatment of HIV infection.
1. A pharmaceutical composition comprising a polypeptide comprising:
a first domain comprising a portion of soluble CD4, wherein said portion of soluble CD4 comprises the D1D2 domain of soluble CD4;
a second domain comprising a human immunodeficiency virus (HIV) gp41 functional domain-binding sequence selected from the group consisting of N-terminal heptad repeat (NHR)-binding peptides, C-terminal heptad repeat (CHR)-binding peptides and fusion peptide (FP)-binding peptides; and
a flexible linker linking the amino acid sequences of said first domain and said second domain, wherein said linker comprises the amino acid sequence (GGGGS) n , wherein n is an integer between 2 and 8;
wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:37-62.
2. The pharmaceutical composition of claim 1 wherein said composition further includes at least one pharmaceutically acceptable excipient.
3. A method of treating a viral infection comprising:
administering an effective dose of the pharmaceutical composition of claim 1 to an individual exposed to an HIV infection;
inactivating said HIV, and
blocking entry of said HIV into a target cell, thereby treating said viral infection.