We identified induction of the ABC transporters, ABCG2 and ABCB1, as a potential mechanism of de novo and acquired resistance, thus reducing potency.
All of the currently available anti-HIV drugs are far from ideal, and we still face problems of acute and chronic side effects, patient compliance issues, drug resistance, cost, and potency.
From the first identification of substrate-derived peptide inhibitors to the complex, macrocyclic compounds, including paritaprevir and grazoprevir, that are currently available, the field has used structure-based design to confront the issues of potency, resistance and pharmacokinetics.
20, 64 Despite this increased potency, resistance can still occur.
This might also lead to the problem of multidrug resistance thereby reducing potency of a drug with repeated administration.
In addition, we have characterized how resistance susceptibility and potency of the NS3/4A inhibitors are dependent on both the P2* extension and the macrocyclization.
When they are used in combination with antimicrobial agents, inhibitors of these pumps should reverse resistance, enhancing the potency and expanding the spectrum of activity of antimicrobial agents while decreasing the emergence of new resistance [ 50].
In addition, our findings support the notion that 17-AAG as well as other HSP90 inhibitors are promising antileishmanial drugs that could be used alone or as synergistic drugs with the aim of reducing toxicity and resistance and increase potency [ 132, 133].
The establishment and utilization of biotechnology in the field of haemophilia potentially offers novel agents, as well as therapeutics with longer half-lives, increased potency and resistance to inactivation, increased secretion, and reduced resistance to inhibitors.
Thus, virological failure may result from suboptimal adherence, poor drug potency, drug resistance, or a combination of these factors [3].
