Publications by authors named "Joyce A Murphy"
Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1--octadecyl-2--benzyl--glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043.
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- Early antiviral treatments like intravenous remdesivir (RDV) have shown promise in reducing severe COVID-19 cases, and an oral form of RDV may allow for earlier treatment in non-hospitalized patients.
- Researchers synthesized and evaluated oral analogs of RDV that are stable in plasma, specifically a compound named 1-octadecyl-2-benzyl-glyceryl-3-RVn, which effectively reduced viral load in infected mice.
- The study indicates that modifications, such as adding specific substituents to the analogs, can enhance antiviral activity, supporting further development of these compounds as effective oral treatments for SARS-CoV-2.
The integration of 'long-term' adiposity signaling with the 'short-term' meal-related signal cholecystokinin (CCK) is proposed to involve descending hypothalamic projections to areas of the caudal brainstem (CBS) that regulate the amount of food consumed during a single meal. One such projection extends from cell bodies in the hypothalamic paraventricular nucleus (PVN) to the nucleus tractus solitarius (NTS), where cells that respond to peripheral CCK are concentrated. Candidate neuronal cell types that may comprise this PVN-NTS projection includes those expressing corticotropin-releasing hormone (CRH) or oxytocin.
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