Whitehead Institute for Biomedical Research

University of Utah Research Foundation

Navigen, Inc.

Merck + Co., Inc.

Medimmune Limited

Istitute Di Ricerche Di Biologia Molecolare P. Angeletti S.p.a.

The United States of America—air Force

Merck Sharp + Dohme Corp.

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Cambridge Antibody Technology Limited

Debra Muir Eckert

Peter S Kim

David C Chan

Vladimir N Malashkevich

Peter A Carr

Tara R Suntoke

Michael S Kay

Brett D Welch

Michael Thomas Jacobsen

Elisabetta Bianchi

Michael D Miller

John W Shiver

Daria Hazuda

Matthew T Weinstock

Michael J Root

Romas Geleziunas

Simon N Lennard

Tracy R Clinton

Rena McKinnon

Vladimir Malashkevich

Daria J Hazuda

Disclosed herein are compositions and methods for inhibiting respiratory syncytial virus (RSV) entry into a host cell. Also provided herein are methods of identifying a peptide that interacts with the N-trimer of RSV F protein.

Compositions and methods related to inhibition of respiratory syncytial virus entry

is a highly lethal filovirus that causes hemorrhagic fever in humans and non-human primates. With no approved treatments or preventatives, the development of an anti-therapy to protect against natural infections and potential weaponization is an urgent unmet global health need. The design, biophysical characterization, and validation of peptide mimics of theN-trimer ('N-trimer mimics') are described herein.

Ebolavirus pre-hairpin intermediate mimics and methods of use

Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Inhibitors of HIV membrane fusion

Described herein are chimeric peptides comprising a soluble trimeric coiled-coil and all or a portion of the N-peptide region of HIV gp41. These molecules are stable, trimeric coiled-coils that inhibit HIV entry into cells, such as human cells. Such peptides can be further assessed to demonstrate their ability to serve as potent anti-HIV therapeutic molecules and thus, as therapeutic molecules or drugs.

Soluble chimeric peptide inhibitors of HIV entry comprising an IZ trimeric coiled-coil peptide and HIV gp41 N-helix coiled-coil peptide

Human scFvs are disclosed which interact with a conformational epitope along the pre-hairpin, N-helix coiled coil structure within the heptad repeat 1 (HR1) region of gp41 of HIV. These antibodies, as well as IgG conversions, are shown to neutralize diverse HIV isolates. Isolated nucleic acid molecules are also disclosed which encode relevant portions of these antibodies, as well as the purified forms of the expressed antibodies or relevant antibody fragments, such as Vand Vchains. The antibody compositions disclosed within this specification may provide for a therapeutic treatment against HIV infection by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV infection. These antibodies will also be useful in assays to identify HIV antiviral compounds as well as allowing for the identification of candidate HIV vaccines, such as HIV peptide vaccines.

Human antibodies interacting with HIV gp41

Peptide inhibitors of HIV entry

Growing community of inventors

Salt Lake City, UT, United States of America

Debra Muir Eckert