0 10 Inhibition Inhibition NNP 11 13 of of IN 14 19 HIV-1 HIV-1 NNP 20 31 replication replication NN 32 34 by by IN 35 46 combination combination NN 47 49 of of IN 50 51 a a DT 52 57 novel novel JJ 58 67 inhibitor inhibitor NN 68 70 of of IN 71 80 TNF-alpha TNF-alpha NNP 81 85 with with IN 86 89 AZT AZT NNP 89 90 . . . 92 95 The the DT 96 101 small small JJ 102 110 molecule molecule NN 111 114 S9a S9a NNP 115 118 was be VBD 119 126 derived derive VBN 127 131 from from IN 132 134 an an DT 135 146 established establish VBN 147 152 tumor tumor NN 153 161 necrosis necrosis NN 162 174 factor-alpha factor-alpha NN 175 176 ( ( ( 176 185 TNF-alpha TNF-alpha NNP 185 186 ) ) ) 187 196 inhibitor inhibitor NN 197 198 ( ( ( 198 207 Canventol Canventol NNP 207 208 ) ) ) 209 211 by by IN 212 223 replacement replacement NN 224 226 of of IN 227 230 the the DT 231 245 isopropylidine isopropylidine NN 246 251 group group NN 252 256 with with IN 257 258 a a DT 259 265 phenyl phenyl NN 266 270 ring ring NN 270 271 . . . 272 275 S9a S9a NNP 276 278 at at IN 279 281 10 10 CD 282 284 to to TO 285 288 100 100 CD 289 291 nM nM NNP 292 301 inhibited inhibit VBD 302 305 HIV HIV NNP 306 316 production production NN 317 319 as as RB 320 328 potently potently RB 329 331 as as IN 332 358 3’-azido-3’-deoxythymidine 3'-azido-3'-deoxythymidine NN 359 360 ( ( ( 360 363 AZT AZT NNP 363 364 ) ) ) 364 365 , , , 366 368 an an DT 369 378 inhibitor inhibitor NN 379 381 of of IN 382 387 viral viral JJ 388 395 reverse reverse JJ 396 409 transcriptase transcriptase NN 409 410 . . . 411 422 Furthermore furthermore RB 422 423 , , , 424 427 S9a S9a NNP 428 431 and and CC 432 435 AZT AZT NNP 436 438 in in IN 439 450 combination combination NN 450 451 , , , 452 454 at at IN 455 465 noncytoxic noncytoxic JJ 466 480 concentrations concentration NNS 481 489 strongly strongly RB 490 499 inhibited inhibit VBD 500 505 HIV-1 HIV-1 NNP 506 517 replication replication NN 518 522 that that WDT 523 526 was be VBD 527 531 more more JJR 532 536 than than IN 537 545 additive additive JJ 546 549 and and CC 550 563 substantially substantially RB 564 573 prolonged prolong VBD 574 577 the the DT 578 588 appearance appearance NN 589 591 of of IN 592 597 virus virus NN 598 602 both both CC 603 605 in in IN 606 613 acutely acutely RB 614 622 infected infected JJ 623 627 CD4+ cd4+ JJ 628 639 lymphocytes lymphocyte NNS 640 641 ( ( ( 641 645 SupT SupT NNP 645 646 ) ) ) 647 649 in in IN 650 657 culture culture NN 658 661 and and CC 662 664 in in IN 665 675 peripheral peripheral JJ 676 681 blood blood NN 682 693 mononuclear mononuclear JJ 694 699 cells cell NNS 700 701 ( ( ( 701 706 PBMCs PBMC NNP 706 707 ) ) ) 708 716 infected infect VBN 717 721 with with IN 722 723 a a DT 724 731 primary primary JJ 732 737 HIV-1 HIV-1 NNP 738 745 isolate isolate NN 745 746 . . . 747 750 S9a S9a NNP 751 760 inhibited inhibit VBD 761 770 TNF-alpha TNF-alpha NNP 771 786 promoter-driven promoter-driven JJ 787 795 reporter reporter NN 796 800 gene gene NN 801 809 activity activity NN 809 810 . . . 811 813 It it PRP 814 817 was be VBD 818 826 proposed propose VBN 827 831 that that IN 832 835 the the DT 836 845 mechanism mechanism NN 846 848 of of IN 849 858 antiviral antiviral JJ 859 865 action action NN 866 868 of of IN 869 872 S9a S9a NNP 873 876 was be VBD 877 879 on on IN 880 883 the the DT 884 888 host host NN 889 893 cell cell NN 893 894 , , , 895 897 by by IN 898 906 blocking block VBG 907 916 TNF-alpha TNF-alpha NNP 917 930 transcription transcription NN 931 934 via via IN 935 936 a a DT 937 948 Tat-induced tat-induced JJ 949 964 tar-independent tar-independent JJ 965 969 loop loop NN 969 970 , , , 971 976 which which WDT 977 986 decreases decrease VBZ 987 997 downstream downstream JJ 998 1007 NF-kappaB NF-kappaB NNP 1008 1018 activation activation NN 1019 1021 of of IN 1022 1027 HIV-1 HIV-1 NNP 1028 1032 long long JJ 1033 1041 terminal terminal JJ 1042 1048 repeat repeat NN 1049 1050 ( ( ( 1050 1053 LTR LTR NNP 1053 1054 ) ) ) 1054 1055 . . . 1056 1059 S9a S9a NNP 1060 1063 was be VBD 1064 1072 superior superior JJ 1073 1075 to to TO 1076 1079 the the DT 1080 1085 first first JJ 1086 1096 generation generation NN 1097 1105 compound compound NN 1106 1115 Canventol Canventol NNP 1115 1116 , , , 1117 1122 which which WDT 1123 1126 was be VBD 1127 1135 superior superior JJ 1136 1138 to to TO 1139 1142 the the DT 1143 1150 natural natural JJ 1151 1159 compound compound NN 1160 1171 sarcophytol sarcophytol NN 1172 1173 A a NN 1173 1174 , , , 1175 1188 demonstrating demonstrate VBG 1189 1193 that that IN 1194 1201 further further JJ 1202 1217 structure-based structure-based JJ 1218 1229 enhancement enhancement NN 1230 1232 of of IN 1233 1240 potency potency NN 1241 1243 of of IN 1244 1249 these these DT 1250 1259 compounds compound NNS 1260 1262 is be VBZ 1263 1271 feasible feasible JJ 1271 1272 . . . 1273 1277 This this DT 1278 1283 study study NN 1284 1292 suggests suggest VBZ 1293 1294 a a DT 1295 1306 therapeutic therapeutic JJ 1307 1315 approach approach NN 1316 1323 against against IN 1324 1328 AIDS AIDS NNP 1329 1331 by by IN 1332 1343 application application NN 1344 1346 of of IN 1347 1350 two two CD 1351 1356 drugs drug NNS 1356 1357 , , , 1358 1361 one one CD 1362 1369 against against IN 1370 1371 a a DT 1372 1380 cellular cellular JJ 1381 1384 and and CC 1385 1388 the the DT 1389 1394 other other JJ 1395 1396 a a DT 1397 1402 viral viral JJ 1403 1409 target target NN 1409 1410 , , , 1411 1416 which which WDT 1417 1420 may may MD 1421 1428 provide provide VB 1429 1431 an an DT 1432 1440 approach approach NN 1441 1443 to to TO 1444 1447 the the DT 1448 1455 problem problem NN 1456 1458 of of IN 1459 1467 frequent frequent JJ 1468 1477 emergence emergence NN 1478 1480 of of IN 1481 1490 resistant resistant JJ 1491 1499 variants variant NNS 1500 1502 to to TO 1503 1515 combinations combination NNS 1516 1518 of of IN 1519 1524 drugs drug NNS 1525 1529 that that WDT 1530 1536 target target VBP 1537 1541 only only RB 1542 1545 HIV HIV NNP 1546 1551 genes gene NNS 1551 1552 . . .