Compositions and methods for treating arenavirus infection
AssigneesChildren's Medical Center Corporation, Dana-Farber Cancer Institute, Inc.
InventorsJONATHAN ABRAHAM, STEPHEN HARRISON, KAI WUCHERPFENNIG
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Abstract
The invention generally provides compositions and methods of treating or preventing an arenavirus infection, using an agent that inhibits binding of an arenavirus glycoprotein 1 (GP1) polypeptide to transferrin receptor 1 (TfR1). The invention also provides methods of designing or identifying therapeutic agents that bind to or target a GP1 receptor-binding site (RBS) to inhibit arenavirus attachment to a cell, and therapeutic agents identified using the methods.
Claims28
An isolated antibody or antigen-binding fragment thereof that specifically binds arenavirus glycoprotein 1 (GP1), the antibody comprising one or more complementary determining regions (CDR) selected from
- CDR H1 sequence
- GFTFGTSI
- CDR H2 sequence
- ISHDESRK
- CDR H3 sequence
- AKDLSPPYSYAWDIFQYW
- CDR L1 sequence
- QSVLYSSRSDNKY
- CDR L2 sequence
- WAS
- CDR L3 sequence
- QQYYSSPPTF
- CDR H1 sequence
- GFTFSSA
- CDR H2 sequence
- IWSDGSNE
- CDR H3 sequence
- ATDKTYVSGYTSTWYYFNY
- CDR L1 sequence
- QSIDNW
- CDR L2 sequence
- KAS;
- and
- CDR L3 sequence
- QHRT.
7-13. (canceled)
16-17. (canceled)
(canceled)
A method of inhibiting or preventing binding of a transferrin receptor 1 (TfR1) and a glycoprotein 1 (GP1) of one species of New World arenavirus, the method comprising contacting a TfR1 with an antibody or antigen-binding fragment thereof generated by an immune response to a glycoprotein 1 (GP1) of a second species of New World arenavirus.
23-24. (canceled)
A method of treating or preventing a New World arenavirus infection, the method comprising administering to a subject infected or at risk of infection with one species of New World arenavirus an antibody or antigen-binding fragment thereof generated by an immune response to a second species of New World arenavirus.
26-39. (canceled)
41-42. (canceled)
44-52. (canceled)
An immunogenic composition or vaccine comprising a polypeptide comprising a TfR1 binding site of a New World arenavirus GP1, wherein the TfR1 binding site comprises amino acids 87-235 of JUNV GP1 or corresponding amino acids of an arenavirus GP1.
54-58. (canceled)
An in silico method for identifying an agent that inhibits binding of a New World arenavirus GP1 to a transferrin receptor, the method comprising:
- a) generating a three-dimensional representation of a transferrin receptor structural binding pocket using the atomic coordinates of a New World arenavirus surface envelope glycoprotein amino acid residues in the sequence;
- and
- b) employing the three-dimensional structure to design or select an agent that inhibits binding.
(canceled)
Dependencies are inferred from the claim text.