We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC(50) = 7.4 nM, SI = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC(50) = 7.4 nM and EC(50) = 0.46 nM, respectively.

(+)-Calanolide A ( 1) as a natural product was previously found as an inhibitor of HIV-1 reverse transcriptase. In our further investigation of its template, racemic 11-demethyl-12-oxo calanolide A ( 15), which had two fewer chiral carbon centers at the C-11 and C-12 positions than (+)-calanolide A, had a comparably inhibitory activity and better therapeutic index (EC 50 = 0.11 microM, TI = 818) against HIV-1 in vitro. A library based on its structural core was then designed and synthesized with introduction of nine diversity points in this article. The evaluations of anti-HIV-1 activity in vitro concluded their structure-activity relationships (SARs). A novel compound (10-bromomethyl-11-demethyl-12-oxo calanolide A, 123) was identified to have much higher inhibitory potency and therapeutic index (EC 50 = 2.85 nM, TI > 10,526) than those of the class compound against HIV-1. This finding provided a very important clue that modifications of the C ring at the C-10 position may be conducted to obtain drug candidates with better activity against HIV-1.

Avian gyrovirus 2 (AGV2) was the second member of the viral genus Cyclovirus to be discovered. This virus poses a significant potential threat to humans and poultry due to its global dissemination and infectiousness. We used three overlapping polymerase chain reactions (PCRs) to map the whole genome of AGV2. We then modelled the evolutionary history of these novel sequence data in the context of related sequences from GenBank. We analysed the viral protein characteristics of the different phylogenetic groups and explored differences in evolutionary trends between Chinese strains and strains from other countries. We obtained 17 avian-sourced AGV2 whole genomes from different regions of China from 2015 to 2016. Phylogenetic analyses of these Chinese AGV2 sequences and related sequences produced four distinct groups (A–D) with significant bootstrap values. We also built phylogenies using predicted viral protein sequences. We found a potential hypervariable region in VP1 at sites 288–314, and we identified the amino acid changes responsible for the distinct VP2 and VP3 groups. Three new motifs in the AGV2 5′-UTR direct repeat (DR) region were discovered and grouped. The novel characteristics and diverse research on the AGV2 genome provide a valuable framework for additional research.