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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. 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HIV Data and Statistics. Available online: https:\/\/www.who.int\/teams\/global-hiv-hepatitis-and-stis-programmes\/hiv\/strategic-information\/hiv-data-and-statistics."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJMp1916753","article-title":"Four decades of HIV\/AIDS\u2014Much accomplished, much to do","volume":"383","author":"Fauci","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"167507","DOI":"10.1016\/j.jmb.2022.167507","article-title":"Novel RNase H inhibitors blocking RNA-directed strand displacement DNA synthesis by HIV-1 reverse transcriptase","volume":"434","author":"Kang","year":"2022","journal-title":"J. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1002\/med.21544","article-title":"Challenges and approaches in the discovery of human immunodeficiency virus type-1 non-nucleoside reverse transcriptase inhibitors","volume":"39","author":"Battini","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1021\/acs.jmedchem.1c01758","article-title":"Contemporary medicinal chemistry strategies for the discovery and development of novel HIV-1 non-nucleoside reverse transcriptase inhibitors","volume":"65","author":"Wang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.coph.2020.10.009","article-title":"Non-nucleoside reverse transcriptase inhibitors (NNRTIs): A brief overview of clinically approved drugs and combination regimens","volume":"54","author":"Vanangamudi","year":"2020","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/cmdc.201800577","article-title":"Recent advances in the design and development of non-nucleoside reverse transcriptase inhibitor scaffolds","volume":"14","author":"Shirvani","year":"2019","journal-title":"ChemMedChem"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.apsb.2019.11.010","article-title":"Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): Our past twenty years","volume":"10","author":"Zhuang","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.coph.2020.09.017","article-title":"Recent discoveries in HIV-1 reverse transcriptase inhibitors","volume":"54","author":"Gu","year":"2020","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1007\/s40265-017-0820-3","article-title":"Elsulfavirine: First global approval","volume":"77","year":"2017","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.2147\/DDDT.S65596","article-title":"Pharmacokinetics and tolerability of the new second-generation nonnucleoside reverse- transcriptase inhibitor KM-023 in healthy subjects","volume":"8","author":"Cha","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1021\/acs.chemrev.0c00967","article-title":"Avoiding drug resistance in HIV reverse transcriptase","volume":"121","author":"Cilento","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7991","DOI":"10.1021\/acs.jmedchem.6b00738","article-title":"Design, synthesis, and evaluation of thiophene[3,2-d]pyrimidine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors with significantly improved drug resistance profiles","volume":"59","author":"Kang","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, X.J., Lu, L.H., Wang, R.R., Wang, Y.P., Luo, R.H., Cong Lai, C., Yang, L.M., He, Y.P., and Zheng, Y.T. (2013). DB-02, a C-6-cyclohexylmethyl substituted pyrimidinone HIV-1 reverse transcriptase inhibitor with nanomolar activity, displays an improved sensitivity against K103N or Y181C than S-DABOs. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081489"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104041","DOI":"10.1016\/j.bioorg.2020.104041","article-title":"Design, synthesis and anti-HIV evaluation of 5-alkyl- 6-(benzo[d][1,3]dioxol-5-alkyl)-2-mercaptopyrimidin-4(3H)-ones as potent HIV-1 NNRTIs","volume":"102","author":"Li","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0166-0934(88)90134-6","article-title":"Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds","volume":"20","author":"Pauwels","year":"1988","journal-title":"J. Virol. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1128\/AAC.40.6.1491","article-title":"Human serum alpha 1 acid glycoprotein reduces uptake, intracellular concentration, and antiviral activity of A-80987, an inhibitor of the human immunodeficiency virus type 1 protease","volume":"40","author":"Bilello","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzym. Regul."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00375-19","DOI":"10.1128\/JVI.00375-19","article-title":"Advances toward curing HIV-1 infection in tissue reservoirs","volume":"94","author":"Henderson","year":"2020","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.4049\/jimmunol.176.9.5644","article-title":"Differential restoration of myeloid and plasmacytoid dendritic cells in HIV-1-infected children after treatment with highly active antiretroviral therapy","volume":"176","author":"Zhang","year":"2006","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dalmau, J., Codo\u00f1er, F.M., Erkizia, I., Pino, M., Pou, C., Paredes, R., Clotet, B., Martinez-Picado, J., and Prado, J.G. (2012). In-depth characterization of viral isolates from plasma and cells compared with plasma circulating quasispecies in early HIV-1 infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032714"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00683-20","DOI":"10.1128\/JVI.00683-20","article-title":"Comparative circulation dynamics of the five main HIV types in China","volume":"94","author":"Vrancken","year":"2020","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1128\/AAC.38.5.1107","article-title":"Protein binding of human immunodeficiency virus protease inhibitor KNI-272 and alteration of its in vitro antiretroviral activity in the presence of high concentrations of proteins","volume":"38","author":"Kageyama","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2174\/1570162X18666200620211922","article-title":"The new NNRTI ACC007 combined with lamivudine and tenofovir disoproxil fumarate show synergy anti-HIV activity in vitro","volume":"18","author":"Huang","year":"2020","journal-title":"Curr. HIV Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1016\/j.drudis.2021.06.006","article-title":"Structural insights into understudied human cytochrome P450 enzymes","volume":"26","author":"Machalz","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_27","first-page":"391","article-title":"The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects","volume":"76","author":"Lynch","year":"2007","journal-title":"Am. Fam. Physician"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2390\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:05:25Z","timestamp":1760144725000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,28]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["v14112390"],"URL":"https:\/\/doi.org\/10.3390\/v14112390","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,28]]}}}