Merck + Co., Inc.

Joanne E Tomassini

John J Baldwin

Harold G Selnick

Gerald S Ponticello

Edward M Scolnick

Joseph V Hughes

Dioxobutanoic acids substituted with piperidine or similar N-substituted saturated cycloalkyls are found to inhibit the cap-dependent endonuclease of influenza virus. These compounds are useful in the prevention or treatment of infection by influenza virus and the treatment of influenza, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating influenza and methods of preventing or treating infection by influenza virus are also described.

Dioxobutanoic acid derivatives as inhibitors of influenza endonuclease

Dioxobutanoic acids substituted with piperidine or similar N-substituted saturated cycloalkyls are found to inhibit the cap-dependent endonuclease of influenza virus. These compounds are useful in the prevention or treatment of infection by influenza virus and the treatment of influenza, either as compound, pharmaceutically acceptable salts,. pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating influenza and methods of preventing or treating infection by influenza virus are also described.

A surface structural protein of Hepatitis A Virus (HAV) has been isolated and characterized from virus grown in tissue culture. This 33,000 dalton viral protein (VP-1) reacts with immune HAV sera and monoclonal antibodies that neutralize HAV infectivity. The VP-1 is usable for the preparation of a polypeptide subunit vaccine for HAV. Hybridoma cells were made which produced monoclonal antibodies to HAV or VP-1. These monoclonal antibodies were found to neutralize the infectivity of HAV and to compete with polyclonal antibody derived from human HAV immune sera. The monoclonal antibodies are useful for the neutralization of infectious HAV, the detection of antibodies to neutralizing sites on HAV, and the diagnoses of HAV disease in humans and other susceptible hosts.

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Lansdale, PA, United States of America

Joanne E Tomassini