Viral infection inhibitor targeting integrase N-terminal domain
View Patent ↗The object of the present invention is to provide a screening method of a new integrase inhibitor being able to inhibit an HIV infection before the reverse transcription step and having a pharmaceutical site of action totally different from those of traditional integrase inhibitors, a new integrase inhibitor being obtainable by the screening method, and pharmaceutical constituents containing the integrase inhibitor and DNA encoding the integrase inhibitor being greatly expected as new remedies for AIDS. A peptide which specifically binds to a peptide at N-terminal domain of retroviral integrase was screened by phage display method, and as a result of the screening, a peptide being able to inhibit the infection and the proliferation of retroviruses such as HIV-1 before the reverse transcription reaction is obtained.
1. A retrovirus comprising a whole or a part of an N-terminal domain of a mutant retroviral integrase, wherein the mutant retroviral integrase comprises a mutation of SEQ ID NO:2 selected from the group consisting of Y15A, wherein the tyrosine at position 15 is substituted with alanine; Y15T, wherein the tyrosine at position 15 is substituted with threonine; P29F, wherein the proline at position 29 is substituted with phenylalanine; V32E, wherein the valine at position 32 is substituted with glutamic acid;
and I36E, wherein the isoleucine at position 36 is substituted with glutamic acid.
2. The retrovirus of claim 1 , wherein the mutant integrase is Y15A.
3. The retrovirus of claim 1 , wherein the mutant integrase is Y15T.
4. The retrovirus of claim 1 , wherein the mutant integrase is P29F.
5. The retrovirus of claim 1 , wherein the mutant integrase is V32E.
6. The retrovirus of claim 1 , wherein the mutant integrase is I36E.