Many Christians today only associate the idea of stewardship with sermons they have heard about church budgets and building programs. But the idea of biblical stewardship is about something much more expansive. It is where the concepts of faith, work and economics intersect. There are four important principles about biblical stewardship we must understand: the principle of ownership, the principle of responsibility, the principle of accountability, and the principle of reward. As Christians in the 21st century, we need to embrace this larger biblical view of stewardship, which goes beyond church budgets or building projects, though important; it connects everything we do with what God is doing in the world. We need to be faithful stewards of all God has given us within the opportunities presented through his providence to glorify Him, serve the common good and further His Kingdom.
Resistant viruses are able to replicate under selective pressure better than sensitive viruses and, in this manner, of being positively selected. However, resistance mutations may negatively affect the function of the targeted protein (protease, reverse transcriptase, integrase and so on.), in this way creating a reduction of viral “fitness” (for example, relative efficiency of replication). Thus, when resistance mutations accumulate in the virus, its replication, transmission and virulence may be impeded compared with wild-type virus without drug resistance mutations (Turner et al., 2003). Nevertheless, minimizing the negative effect of these resistance mutations on the virus’ fitness can be done as an outcome of using secondary mutations that may lessen the fitness cost of single mutations. The effect of secondary resistance mutations on viral fitness and their accumulation have been assessed on account of numerous resistance mutations in integrase and reverse transcriptase (Brenner et al., 2002). In these illustrations, primary mutations may give resistance, and afterward a second mutation may perhaps increase fitness, permitting a recovery even with the presence of antiretroviral medications (Fransen et al., 2009).
4.7 REVERSE TRANSCRIPTASE AS A DRUG TARGET
The first antiretroviral drugs to be used were NRTIs. These agents are nucleoside analogs that do not have a 3′ OH moiety in the ribose ring, which recognizes them from physiological dNTP substrates. NRTIs mediate the inhibition of reverse transcriptase throughout their fusion into the nascent DNA strand amid reverse transcription. As a result, for this incorporation, termination of transcription occurs, thereby blocking viral replication. Nucleotide reverse transcriptase inhibitors, such as tenofovir, act by the same way as NRTIs (Go”tte and Wainberg, 2000).
A different mechanism for the inhibition of reverse transcription is mediated by Non-nucleoside reverse transcriptase inhibitors (NNRTIs) for example, via binding to non-catalytic enzyme sites. The NNRTIs don’t require phosphorylation for their activity and don’t fuse into growing DNA strands. The most important chemical components of NNRTIs have been produced in light of molecular and structures models of reverse transcriptase (Go”tte and Wainberg, 2000). Following chemical modifications or changes to these parts produced NNRTIs with enhanced activity against
