Ayisi N K, Gupta V S, Meldrum J B, Taneja A K, Babiuk L A
Antimicrob Agents Chemother. 1980 Apr;17(4):558-66. doi: 10.1128/AAC.17.4.558.
The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), 5-ethyl-2'-deoxyuridine (EtUdR), adenine arabinoside (Ara-A), and phosphonoacetic acid (PAA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). MMUdR was more potent than Ara-A and PAA but less active than EtUdR and IUdR against HSV-1 in rabbit kidney (RK-13) cells. In Vero cells, the antiviral activities of MMUdR, Ara-A, and PAA against HSV-1 were of the same order of magnitude. The antiviral potency against HSV-2 varied with the strain of virus used. All strains of HSV-2 were markedly inhibited by EtUdR and IUdR and to a lesser degree by PAA. However, considerable variation was noticed in the susceptibility of HSV-2 strains to Ara-A and MMUdR. Interaction of MMUdR with Ara-A, EtUdR, IUdR, and PAA was investigated by the method of response isobolograms. MMUdR showed synergistic activity in combination with Ara-A and PAA but antagonistic activity in combination with EtUdR and IUdR against herpesviruses. Minimum toxic dose (concentration required to produce definite evidence of microscopic cytotoxicity in rapidly growing RK-13 cells) was determined for each compound and was found to be 512, 172, 64, 8, and less than 0.5 microgram/ml for MMUdR, PAA, Ara-A, EtUdR, and IUdR, respectively. MMUdR was found to have the maximum antiviral index against HSV-1 (512) and HSV-2 strains X-265 (102) and ATCC (85). Antiviral index was defined as the minimum toxic dose divided by the dose that reduced plaque numbers by 50%.
将5-甲氧基甲基-2'-脱氧尿苷（MMUdR）的抗病毒活性与5-碘-2'-脱氧尿苷（IUdR）、5-乙基-2'-脱氧尿苷（EtUdR）、阿糖腺苷（Ara-A）和膦甲酸（PAA）针对单纯疱疹病毒1型（HSV-1）和2型（HSV-2）的活性进行了比较。在兔肾（RK-13）细胞中，MMUdR对HSV-1的活性比Ara-A和PAA更强，但比EtUdR和IUdR弱。在非洲绿猴肾细胞（Vero细胞）中，MMUdR、Ara-A和PAA对HSV-1的抗病毒活性处于同一数量级。针对HSV-2的抗病毒效力因所用病毒株而异。所有HSV-2毒株均受到EtUdR和IUdR的显著抑制，PAA的抑制程度较小。然而，HSV-2毒株对Ara-A和MMUdR的敏感性存在相当大的差异。采用反应等效应图法研究了MMUdR与Ara-A、EtUdR、IUdR和PAA的相互作用。MMUdR与Ara-A和PAA联合使用时表现出协同活性，但与EtUdR和IUdR联合使用时对疱疹病毒表现出拮抗活性。测定了每种化合物的最小毒性剂量（在快速生长的RK-13细胞中产生明确的显微镜下细胞毒性证据所需的浓度），发现MMUdR、PAA、Ara-A、EtUdR和IUdR的最小毒性剂量分别为512、172、64、8和小于0.5微克/毫升。发现MMUdR针对HSV-1（512）以及HSV-2毒株X-265（102）和美国典型培养物保藏中心（ATCC）毒株（85）具有最大的抗病毒指数。抗病毒指数定义为最小毒性剂量除以使蚀斑数量减少50%的剂量。
