Current status of the small molecule anti-HIV drugs in the pipeline or recently approved.

Autor: Umumararungu T; Department of Industrial Pharmacy, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Rwanda. Electronic address: umumararungut@yahoo.fr., Nyandwi JB; Department of Pharmacology and Toxicology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Rwanda; East African Community Regional Centre of Excellence for Vaccines, Immunization and Health Supply Chain Management, Kigali, Rwanda., Katandula J; Department of Pharmacology and Toxicology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Rwanda., Twizeyimana E; Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Rwanda., Claude Tomani J; Department of Chemistry, School of Science, College of Science and Technology, University of Rwanda, Rwanda., Gahamanyi N; Department of Biology, School of Science, College of Science and Technology, University of Rwanda, Rwanda., Ishimwe N; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA., Olawode EO; Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, 18301 N Miami Ave #1, Miami, FL 33169, USA., Habarurema G; Department of Chemistry, School of Science, College of Science and Technology, University of Rwanda, Rwanda., Mpenda M; Department of Pharmacology and Toxicology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Rwanda., Uyisenga JP; Department of Biology, School of Science, College of Science and Technology, University of Rwanda, Rwanda., Saeed SI; Faculty of Veterinary Science, University of Nyala, P.O. Box: 155, Nyala, Sudan; Nanotechnology in Veterinary Medicine (NanoVet) Research Group, Faculty of Veterinary Medicine, University Malaysia Kelantan, Kelantan 16100, Pengkalan Chepa, Malaysia.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Sep 01; Vol. 111, pp. 117860. Date of Electronic Publication: 2024 Jul 29.
DOI: 10.1016/j.bmc.2024.117860
Abstrakt: Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS) with high morbidity and mortality rates. Treatment of AIDS/HIV is being complicated by increasing resistance to currently used antiretroviral (ARV) drugs, mainly in low- and middle-income countries (LMICs) due to drug misuse, poor drug supply and poor treatment monitoring. However, progress has been made in the development of new ARV drugs, targeting different HIV components (Fig. 1). This review aims at presenting and discussing the progress made towards the discovery of new ARVs that are at different stages of clinical trials as of July 2024. For each compound, the mechanism of action, target biomolecule, genes associated with resistance, efficacy and safety, class, and phase of clinical trial are discussed. These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new classes which can delay the development of resistance.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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