Journal
VIRUSES-BASEL
Volume 14, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/v14112390
Keywords
K-5a2; HIV-1; NNRTI; pharmacodynamics; pharmacokinetics; acute toxicity
Categories
Funding
- National Natural tion of China (NSFC) [81903453, 81973181, 82060670]
- Shandong Provincial Foundation [ZR2020YQ61, ZR2020JQ31, ZR2019BH011]
- National Key RD Program [2021YFC2301703]
- Yunnan Key Research and Development Program [202103AQ100001]
- Qilu Young Scholars Program of Shandong University
- Taishan gram at Shandong Province
- Project of Innovative Research Team of Yunnan [202005AE160005]
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K-5a2 is a potential anti-HIV drug with high anti-HIV-1 activity, synergistic effects with other antiviral drugs, and favorable pharmacokinetics and safety profiles.
HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) area key component of the current HIV-1 combination drug regimens. Although they exhibit potent anti-HIV-1 activity and modest toxicity, the emergence of mutant strains limits their application in clinical. Our previous research efforts contributed to the identification of compound K-5a2, which exhibits nanomolar activity in HIV-1-infected MT-4 cells. In this study, K-5a2 was shown to have a high level of anti-HIV-1 activity against various lab-adapted strains and clinical isolate strains, being comparable to ETR. Moreover, we showed the feasibility of K-5a2 as a preclinical anti-HIV-1 candidate by establishing its synergistic or additive anti-HIV-1 activity in combination with other representative anti-HIV-1 drugs and candidates. In addition, K-5a2 exhibited no inhibitory activity to the primary CYP isoforms and favorable pharmacokinetics. Taken together, its robust anti-HIV-1 potency, synergistic or additive effects with other anti-HIV drugs, and favorable pharmacokinetic and safety profiles make K-5a2 a potent alternative drug for HIV/AIDS treatment.
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