The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Jan. 31, 2023

Filed:

Mar. 02, 2021
Applicant:

National Technology & Engineering Solutions of Sandia, Llc, Albuquerque, NM (US);

Inventors:

Brooke Nicole Harmon, Livermore, CA (US);

Oscar Negrete, Livermore, CA (US);

Joseph S. Schoeniger, Oakland, CA (US);

Edwin A. Saada, Dublin, CA (US);

Attorneys:
Primary Examiner:
Assistant Examiner:
Int. Cl.
CPC ...
A61K 31/496 (2006.01); A61P 31/14 (2006.01); A61K 31/53 (2006.01); A61K 31/428 (2006.01); A61K 31/426 (2006.01); A61K 9/00 (2006.01);
U.S. Cl.
CPC ...
A61K 31/496 (2013.01); A61K 9/0029 (2013.01); A61K 9/0053 (2013.01); A61K 31/426 (2013.01); A61K 31/428 (2013.01); A61K 31/53 (2013.01); A61P 31/14 (2018.01);
Abstract

An in vitro assay was designed to measure the activity of the alphavirus non-structural protein 2 (nsP2), which is the viral protease and is required for viral replication. By taking advantage of fluorescence-resonance energy transfer between two proteins, a protease cleavage assay was generated. This was utilized for high-throughput screening of 40,000 small molecules. Inhibitors were validated using cell-based assays to measure alphavirus infection and cytotoxicity. Certain compounds were then characterized for anti-viral efficacy in various cell lines in numerous assays. Compounds were tested against Chikungunya virus, Venezuelan Equine Encephalitis virus, Rift Valley Fever virus, and Zika virus. Three compounds (compounds I, II, and III) showed pan-alphavirus anti-viral efficacy at concentrations that did not result in cell toxicity. An additional compound, structure IV, showed broad spectrum inhibition of all viruses tested. Pharmaceutical preparations and methods of treatment including these compounds are provided herein.


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