Rationally designed multitarget anti-HIV agents.

Multitarget-directed ligands (MTDLs), an emerging and appealing drug discovery strategy, utilizing a single chemical entity to inhibit multitargets, was confirmed to be effective in reducing the likelihood of drug resistance, diminishing problems of dosing complexity, drug-drug interactions and toxicities, as well as improving patient compliance. The exploration of MTDL strategy should be valuable in anti-HIV drug discovery. In this article, current knowledge and strategies for the rational design of the multitarget and selective anti-HIV agents are described and a number of illustrative examples are given. Moreover, the challenges, limitations and outlook of such novel drug design strategies are also presented, with a goal to highlight the representative paradigms in the rational design of MTDLs, and to help medicinal chemists discover the next generation of multitarget anti-HIV agents.