Nicousamide

In retroviruses, strand displacement DNA-dependent DNA polymerization catalyzed by the viral reverse transcriptase (RT) is required to synthesize double-stranded proviral DNA. In addition, strand displacement during RNA-dependent DNA synthesis is critical to generate high-quality cDNA for use in molecular biology and biotechnology. In this work, we show that the loss of RNase H activity due to inactivating mutations in HIV-1 RT (e.g. D443N or E478Q) has no significant effect on strand displacement while copying DNA templates, but has a large impact on DNA polymerization in reactions carried out with RNA templates. Similar effects were observed with β-thujaplicinol and other RNase H active site inhibitors, including compounds with dual activity (i.e., characterized also as inhibitors of HIV-1 integrase and/or the RT DNA polymerase). Among them, dual inhibitors of HIV-1 RT DNA polymerase/RNase H activities, containing a 7-hydroxy-6-nitro-2H-chromen-2-one pharmacophore were found to be very potent and effective strand displacement inhibitors in RNA-dependent DNA polymerization reactions. These findings might be helpful in the development of transcriptomics technologies to obtain more uniform read coverages when copying long RNAs and for the construction of more representative libraries avoiding biases towards 5' and 3' ends, while providing valuable information for the development of novel antiretroviral agents.

Nicousamide, a coumarin-aspirin compound, was proven to have a renal protective effect on diabetic and hypertensive nephropathy. The present study aimed to investigate the anti-hypertensive effect of nicousamide and its action mechanisms. The two-kidney one-clip (2K1C) hypertensive animal model was introduced in this study. Subsequent to treatment with nicousamide for three weeks, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and the plasma concentration of angiotensin II (Ang II), nitric oxide (NO), endothelin-1 (ET-1), nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) was examined. Results showed that nicousamide markedly decreased SBP as well as DBP on renovascular hypertensive rats (P<0.05). Nicousamide also reduced the Ang II and ET-1 concentration (P<0.05) in the plasma of hypertensive rats while increasing the plasma NO level (P<0.05). Nicousamide treatment did not show a marked effect on the NOS and CGRP concentrations in animal plasma (P>0.05).