CYTOMEGALOVIRUS DISINTEGRIN-LIKE PEPTIDES
The present invention relates to methods and compositions for inhibiting the entry of viruses, such as herpesviruses into a host cell. A conserved viral integrin-binding gB disintegrin-like domain has been identified that engages integrins and facilitates viral internalization into the host cell. Therefore, methods and compositions, such as antiviral agents encompassing the conserved gB disintegrin-like domain and antibodies thereto are described. These active agents interfere with the interaction between virions and cellular integrins, thereby inhibiting viral infection of a host cell.
1 . A method of inhibiting viral infection of an animal host cell, the method comprising administering to the host cell an antiviral-effective amount of an active agent selected from the group consisting of a purified, integrin-binding gB disintegin-like peptide and a purified antibody that binds specifically to an integrin-binding, gB disintegrin-like peptide.
2 . The method of claim 1 , wherein the active agent comprises a purified, integrin-binding gB disintegrin-like peptide.
3 . The method of claim 2 , wherein the purified, integrin-binding gB disintegrin-like peptide comprises an amino acid consensus sequence RX 5-8 DLXXFX 5 C (SEQ. ID. NOS: 1-4) or an amino acid sequence at least 80% homologous thereto.
4 . The method of claim 2 , wherein the purified, integrin-binding gB disintegrin-like peptide comprises an amino acid sequence RVCSMAQGTDLIRFERNIVC (SEQ. ID. NO: 5) or an amino acid sequence at least 80% homologous thereto.
5 . The method of claim 2 , wherein the active agent is administered via a route selected from the group consisting of parenterally, orally, subcutaneously, and topically.
6 . The method of claim 1 , wherein the active agent comprises a purified antibody that binds specifically to an integrin-binding, gB disintegrin-like peptide.
7 . The method of claim 6 , wherein the purified antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising the consensus sequence RX 5-8 DLXXFX 5 C (SEQ. ID. NOS: 1-4) or an amino acid sequence at least 80% homologous thereto.
8 . The method of claim 7 , wherein the purified antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising the amino acid sequence RVCSMAQGTDLIRFERNIVC (SEQ. ID. NO: 5) or an amino acid sequence at least 80% homologous thereto.
9 . The method of claim 7 , wherein the purified antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising residues 91-111 of glycoprotein B of human cytomegalovirus.
10 . The method of claim 6 , wherein the purified antibody inhibits engagement of virions with cellular integrins.
11 . The method of claim 6 , wherein the purified antibody inhibits internalization of virus of family Herpesviridae (V.C. 31) into the host cell.
12 . The method of claim 6 , wherein the purified antibody inhibits internalization of virus of family Herpesviridae, sub-family Beta herpesvirinae (V.C. 31.2) into the host cell.
13 . The method of claim 6 , wherein the purified antibody inhibits internalization of virus of family Herpesviridae, sub-family Beta herpesvirinae, genus Cytomegalovirus (V.C. 31.2.1) into the host cell.
14 . The method of claim 6 , wherein a purified monoclonal antibody is administered to the host cell.
15 . The method of claim 6 , wherein a purified polyclonal antibody is administered to the host cell.
16 . A pharmaceutical composition comprising an antiviral-effective amount of an active agent selected from the group consisting of a purified, integrin-binding gB disintegrin-like peptide, wherein the peptide is capable of inhibiting viral internalization into an animal host cell or an antiviral-effective amount and a purified antibody that binds specifically to an integrin-binding, gB disintegrin-like peptide.
17 . The pharmaceutical composition of claim 16 , wherein the active agent comprises a purified, integrin-binding gB disintegrin-like peptide.
18 . The pharmaceutical composition of claim 17 , wherein the purified, integrin-binding gB disintegrin-like peptide comprises an amino acid consensus sequence RX 5-8 DLXXFX 5 C (SEQ. ID. NOS: 1-4) or an amino acid sequence at least 80% homologous thereto.
19 . The pharmaceutical composition of claim 17 , wherein the purified, integrin-binding gB disintegrin-like peptide comprises an amino acid sequence RVCSMAQGTDLIRFERNIVC (SEQ. ID. NO: 5) or an amino acid sequence at least 80% homologous thereto.
20 . The pharmaceutical composition of claim 17 , further comprising, in combination, a pharmaceutical carrier suitable for an administration a route selected from the group consisting of parenterally, orally, subcutaneously, and topically.
21 . The pharmaceutical composition of claim 16 , wherein the active agent comprises a purified antibody that binds specifically to an integrin-binding, gB disintegrin-like peptide.
22 . The pharmaceutical composition of claim 21 , wherein the purified antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising the consensus sequence RX 5-8 DLXXFX 5 C (SEQ. ID. NOS: 1-4) or an amino acid sequence at least 80% homologous thereto.
23 . The pharmaceutical composition of claim 21 , wherein the purified antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising the amino acid sequence RVCSMAQGTDLIRFERNIVC (SEQ. ID. NO: 5) or an amino acid sequence at least 80% homologous thereto.
24 . The pharmaceutical composition of claim 21 , wherein the purified antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising residues 91-111 of glycoprotein B of human cytomegalovirus.
25 . The pharmaceutical composition of claim 21 , wherein the purified antibody inhibits engagement of virions with cellular integrins.
26 . The pharmaceutical composition of claim 21 , wherein the purified antibody is a monoclonal antibody.
27 . The pharmaceutical composition of claim 21 , wherein the purified antibody is a polyclonal antibody.
28 . A purified polypeptide comprising SEQ. ID. NOS: 1-5 or an amino acid sequence having at least 80% homology to SEQ. ID. NOS: 1-5.
29 . A purified antibody that binds specifically to an integrin-binding, gB disintegrin-like peptide.
30 . The purified antibody of claim 29 , wherein the antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising the consensus sequence RX 5-8 DLXXFX 5 C (SEQ. ID. NOS: 1-4) or an amino acid sequence at least 80% homologous thereto.
31 . The purified antibody of claim 29 , wherein the antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising the amino acid sequence RVCSMAQGTDLIRFERNIVC (SEQ. ID. NO: 5) or an amino acid sequence at least 80% homologous thereto.
32 . The purified antibody of claim 29 , wherein the antibody binds selectively to an integrin-binding, gB disintegrin-like peptide comprising residues 91-111 of glycoprotein B of human cytomegalovirus.
33 . The purified antibody of claim 29 , wherein the antibody inhibits engagement of virions with cellular integrins.
34 . The purified antibody of claim 29 , wherein the antibody inhibits internalization of virus of family Herpesviridae (V.C. 31) into host cells.
35 . The purified antibody of claim 29 , wherein the antibody inhibits internalization of virus of family Herpesviridae, sub-family Beta herpesvirinae (V.C. 31.2) into host cells.
36 . The purified antibody of claim 29 , wherein the antibody inhibits internalization of virus of family Herpesviridae, sub-family Beta herpesvirinae, genus Cytomegalovirus (V.C. 31.2.1) into host cells.
37 . The purified antibody of claim 29 , wherein the antibody is a monoclonal antibody.
38 . The purified antibody of claim 29 , wherein the antibody is a polyclonal antibody.