Show simple item record

dc.contributorKao, Cheng C.
dc.creatorOrtiz Alcantara, Joanna M.
dc.date.accessioned2010-07-15T00:11:23Z
dc.date.accessioned2010-07-23T21:43:02Z
dc.date.accessioned2017-04-07T19:57:02Z
dc.date.available2010-07-15T00:11:23Z
dc.date.available2010-07-23T21:43:02Z
dc.date.available2017-04-07T19:57:02Z
dc.date.created2009-05
dc.date.issued2010-07-14
dc.identifier.urihttp://hdl.handle.net/1969.1/ETD-TAMU-2009-05-307
dc.description.abstractThe Severe Acute Respiratory Syndrome (SARS) virus encodes several unusual RNA processing enzymes, including Nsp15, an endoribonuclease that preferentially cleaves 3? of uridylates through a Ribonuclease A-like mechanism. Crystal structures of Nsp15 confirmed that the Nsp15 active site is structurally similar to that of Ribonuclease A. These similarities and our molecular docking analysis lead us to hypothesize that previously characterized Ribonuclease A inhibitors will also inhibit the SARS-CoV Nsp15. Benzopurpurin B, C-467929, C-473872, N-36711, N-65828, N-103018 and Congo red were tested for effects on Nsp15 endoribonuclease activity. A real-time fluorescence assay revealed that the IC50 values for inhibiting Nsp15 were between 0.2 ?M and 40 ?M. Benzopurpurin B, C-473872, and Congo red are competitive inhibitors, according to kinetic studies and were demonstrated to bind SARS-CoV Nsp15 by a differential scanning fluorimetry assay. Benzopurpurin B also inhibited the Nsp15 orthologs from two other coronaviruses: mouse hepatitis virus (MHV) and infectious bronchitis virus. The three compounds reduced infectivity of MHV in L2 cells by 8 to 26 fold. The more effective drugs also caused a decrease in MHV RNA accumulation.
dc.language.isoeng
dc.subjectSmall molecule inhibitors, SARS, Nsp15, endoribonuclease, Coronavirus
dc.titleSMALL MOLECULE INHIBITORS OF THE SARS-COV NSP15 ENDORIBONUCLEASE, MECHANISM OF ACTION AND INSIGHT INTO CORONAVIRUS INFECTION
dc.typeBook
dc.typeThesis


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record