期刊
BIOCHIMIE
卷 189, 期 -, 页码 169-180出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2021.06.011
关键词
HIV-1; CMV; Heterodimers; Human tissues; Viral diseases
资金
- NIH office of AIDS research
- NICHD Intramural Program
- Russian Foundation for Basic Research Projects N DEG [17-54-30016]
- NIH [18-29-08010]
Efficient dual-targeted drugs against both HIV-1 and CMV have been developed, showing low cytotoxicity and effective inhibition of both viruses in cell lines. Further development of such compounds may lead to the development of dual-targeted anti-CMV/HIV-1 drugs.
Despite the development of efficient anti-human immunodeficiency virus-1 (HIV-1) therapy, HIV-1 associated pathogens remain a major clinical problem. Human cytomegalovirus (CMV) is among the most common HIV-1 copathogens and one of the main causes of persistent immune activation associated with dysregulation of the immune system, cerebrovascular and cardiovascular pathologies, and pre-mature aging. Here, we report on the development of dual-targeted drugs with activity against both HIV -1 and CMV. We synthesized seven compounds that constitute conjugates of molecules that suppress both pathogens. We showed that all seven compounds exhibit low cytotoxicity and efficiently inhibited both viruses in cell lines. Furthermore, we chose a representative compound and demonstrated that it efficiently suppressed replication of HIV-1 and CMV in human lymphoid tissue ex vivo coinfected with both viruses. Further development of such compounds may lead to the development of dual-targeted anti-CMV/HIV-1 drugs. (c) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
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