Polypharmacology in HIV inhibition: can a drug with simultaneous action against two relevant targets be an alternative to combination therapy?

HIV infection still has a serious health and socio-economical impact and is one of the primary causes of morbidity and mortality all over the world. HIV infection and the AIDS pandemic are still matters of great concern, especially in less developed countries where the access to highly active antire...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2018-04, Vol.150, p.206-227
Main Authors: de Castro, Sonia, Camarasa, María-José
Format: Article
Language:English
Subjects:
Co-infection
Dual drugs
HIV
Hybrids
Multi-target drugs
Polypharmacology
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Summary:HIV infection still has a serious health and socio-economical impact and is one of the primary causes of morbidity and mortality all over the world. HIV infection and the AIDS pandemic are still matters of great concern, especially in less developed countries where the access to highly active antiretroviral therapy (HAART) is limited. Patient compliance is another serious drawback. Nowadays, HAART is the treatment of choice although it is not the panacea. Despite the fact that it suppresses viral replication at undetectable viral loads and prevents progression of HIV infection into AIDS HAART has several pitfalls, namely, long-term side-effects, drug resistance development, emergence of drug-resistant viruses, low compliance and the intolerance of some patients to these drugs. Moreover, another serious health concern is the event of co-infection with more than one pathogen at the same time (e.g. HIV and HCV, HBV, herpes viruses, etc). Currently, the multi-target drug approach has become an exciting strategy to address complex diseases and overcome drug resistance development. Such multifunctional molecules combine in their structure pharmacophores that may simultaneously interfere with multiple targets and their use may eventually be more safe and efficacious than that involving a mixture of separate molecules because of avoidance or delay of drug resistance, lower incidence of unwanted drug-drug interactions and improved compliance. In this review we focus on multifunctional molecules with dual activity against different targets of the HIV life cycle or able to block replication, not only of HIV but also of other viruses that are often co-pathogens of HIV. The different approaches are documented by selected examples. [Display omitted] •Molecules with dual activity against the same HIV target are discussed.•Multi-target molecules active against two targets of HIV life cycle are summarised.•Drugs with dual concomitant activity against HIV and other co-pathogenic viruses are presented.•Multi-target drugs deserve further exploring as complement to HIV combination therapy.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2018.03.007