Characterization of a Novel HIV-1 Second-Generation Recombinant Form in Men Who Have Sex with Men in Beijing, China.

Cocirculation of multiple subtypes in the same population contributes significantly to the emergence of recombinant viruses. BJ2015EU19, a novel CCR5-tropic human immunodeficiency virus (HIV)-1, second-generation recombinant virus, was isolated from a man who has sex with men in Beijing, China. Phylogenetic analysis of the near full-length genome showed that BJ2015EU19 consisted of seven fragments from CRF01_AE and CRF07_BC.

Identification of a Novel HIV Type 1 CRF01_AE/B'/C Recombinant Isolate in Sichuan, China.

We report in this study a novel HIV-1 unique recombinant virus (XC2014EU01) isolated from an HIV-positive man who infected through heterosexual sex in Sichuan, China. The near full-length genome analyses showed that XC2014EU01 harbored one subtype B segment in pol region and two subtype C segments in gag-pol region in a CRF01_AE backbone. The unique mosaic structure was distinctly different from the other CRF01_AE/B'/C recombinant forms reported.

Design, synthesis and biological evaluation of (E)-3,4-dihydroxystyryl 4-acylaminophenethyl sulfone, sulfoxide derivatives as dual inhibitors of HIV-1 CCR5 and integrase.

Aiming at the limited effectiveness of current clinical therapeutic effect of AIDS, novel series of compounds bearing (E)-3,4-dihydroxystyryl sulfone (or sulfoxide) and anilide fragments were designed and synthesized as dual inhibitors of HIV-1 CCR5/IN. The biological results indicated that several target compounds showed inhibitory activity against HIV-1 Bal (R5) infection in TZM-bl cells. Besides targeting the chemokine receptor on the host cell surface, they also displayed binding affinities with HIV-1 integrase using the surface plasmon resonance (SPR) binding assays.

Near Full-Length Genome Identification of a Novel HIV-1 Unique (B/C) Recombinant Isolate in Sichuan, China.

A novel HIV-1 unique recombinant virus (XC2014EU20) was identified. It was isolated from an HIV-positive man who was infected through heterosexual sex in Sichuan, China. The near full-length genome analyses showed that the novel recombinant was composed of three subtype B regions in a subtype C backbone.

Identification of a Novel CRF01_AE/CRF07_BC Recombinant Form in Men Who Have Sex with Men in Sichuan, China.

A novel second-generation CCR5-tropic HIV-1 recombinant virus (XC2014EU09) was identified here, which was isolated from a HIV-positive man who had sex with men (MSM) in Sichuan, China. Phylogenic analyses showed that XC2014EU09 was composed of two well-established circulating recombinant forms (CRF01_AE and CRF07_BC). Different from the other four reported CRF01_AE/CRF07_BC recombinant forms, three recombinant breakpoints of XC2014EU09 with four fragments were observed in the vpr, env, and nef genes, respectively, as follows: ICRF01_AE (636-5,843 nt), IICRF07_BC (5,844-8,393 nt), IIICRF01_AE (8,394-9,119 nt), and IVCRF07_BC (9,120-9,600 nt).

A stereo configuration-activity study of 3-iodo-4-(2-methylcyclohexyloxy)-6-phenethylpyridin-2(2H)-ones as potency inhibitors of HIV-1 variants.

3-Iodo-4-(2'-methylcyclohexyloxy)-6-phenethylpyridin-2(1H)-ones, as effective non-nucleoside reverse transcriptase inhibitors, were synthesized and resolved with different configurations. Biological results revealed that the trans-racemate 2b exhibited more potent activity than the cis-isomers. Noticeably, the trans-(S,S)-enantiomer 2e turned out to be significantly more potent than its counterpart enantiomer 2d against wild-type and double-mutant strains with high selectivity indexes.

The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of the highly active antiretroviral therapy (HAART) used to treat human immunodeficiency type 1 virus (HIV-1). However, because of the emergence of drug resistance and the adverse effects of current anti-HIV drugs, it is essential to develop novel NNRTIs with an excellent safety profile, improved activity against NNRTI-resistant viruses, and enhanced activity against clinical isolates of different subtypes. Here, we have identified 1-[(benzyloxy)methyl]-6-(3,5-dimethylbenzyl)-5-iodopyrimidine-2,4(1H,3H)-dione (WPR-6), a novel NNRTI with a 50% effective concentration (EC50) of 2 to 4 nM against laboratory-adapted HIV-1 strain SF33 and an EC50 of 7 to 14 nM against nucleoside reverse transcriptase inhibitor-resistant HIV-1 strain 7391 with a therapeutic index of >1 × 10(4).

Novel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains.

Novel 6-substituted-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated. Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs). The diastereoisomers of 26-trans and 26-cis were synthesized separately and confirmed with HPLC and NOESY spectra.

Neutralization sensitivity of HIV-1 subtype B' clinical isolates from former plasma donors in China.

Background: HIV-1 subtype B' isolates have been predominantly circulating in China. Their intra- and inter-subtype neutralization sensitivity to autologous and heterologous plasmas has not been well studied.

Results: Twelve HIV-1 B' clinical isolates obtained from patients were tested for their intra- and inter-subtype neutralization sensitivity to the neutralization antibodies in the plasmas from patients infected by HIV-1 B' and CRF07_BC subtypes, respectively.

Design, synthesis, and biological evaluation of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils as potent HIV-1 non-nucleoside reverse transcriptase inhibitors with an improved drug resistance profile.

Because the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b, and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains.

Inhibitory activity of 9-phenylcyclohepta[d]pyrimidinedione derivatives against different strains of HIV-1 as non-nucleoside reverse transcriptase inhibitors.

Background: The non-nucleoside reverse transcriptase inhibitor (NNRTI), as a major component of the highly active antiretroviral therapy (HAART) to HIV-1 (human immunodeficiency virus type 1) infected patients, required the development of new NNRTIs with improved resistance profile and decreased toxicity. Therefore, a series of novel compounds, 9-phenylcyclohepta[d]pyrimidinedione derivatives (PCPs), were designed based on the chemical structure of TNK-651, to detect anti-HIV-1 activity.

Results: 1-[(benzyloxy)methyl]-9-phenyl-cyclohepta[d] pyrimidinedione (BmPCP) among four PCPs has antiviral activity on laboratory-adapted HIV strains (HIV-1 SF33).

Susceptibility of HIV-1 subtypes B', CRF07_BC and CRF01_AE that are predominantly circulating in China to HIV-1 entry inhibitors.

Background: The B', CRF07_BC and CRF01_AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China.

Methodology/principal Findings: The baseline susceptibility of 14 representative HIV-1 isolates (5 CRF07_BC, 4 CRF01_AE, and 5 B'), most of which were R5 viruses, obtained from drug-naïve patients to HIV entry inhibitors, including two fusion inhibitors (enfuvirtide and C34), two CCR5 antagonists (maraviroc and TAK779) and one CXCR4 antagonist (AMD3100), were determined by virus inhibition assay.

[HIV-1 co-receptor usage of patients experienced anti-retroviral therapy].

Objective: To investigate HIV-1 co-receptor usage in patients experienced anti-retroviral therapy (ART) in Anhui and Henan province of China.

Methods: A total of 45 HIV-1 infected individuals who have experienced ART and 109 un-experienced ART patients from Anhui and Henan province, which were called as treatment group and treatment-negative group, were selected as study subjects. HIV-1 strains were isolated from peripheral blood mononuclear cells of whole blood from patients.

Genetic characterization of three newly isolated CRF07_BC near full-length genomes in China.

Though HIV-1 CRF07_BC rapidly spread in China, there have been few reports about this subtype since its first genetic characterization nearly 10 years ago. It was urgent and necessary to know the current gene variation of circulating CRF07_BC strains. Xinjiang was the main region for the CRF07_BC epidemic and also an ideal region for research on the viral gene evolution.