Viral Prophylaxis in Organ Transplant Patients

Slifkin, Michelle; Doron, Shira; Snydman, David R.

doi:10.1002/chin.200534339

Cited by 10 publications

(14 citation statements)

References 1 publication

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“…Currently available antiviral drugs that might be used to treat EBV infection can be divided into two main classes based on whether they target herpesvirus DNA polymerases or not (14,38,47,55). Acyclic nucleoside and phosphonated nucleotide analogs are incorporated into viral DNA and cause DNA chain termination during viral DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

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Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication

Wang

Roy

Gershburg

et al. 2009

J Virol

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Section: Discussionmentioning

confidence: 99%

“…There is, therefore, a strong interest in MBV because of its favorable toxicity profile as well as efficacy (32,63). Moreover, since EBV as well as HCMV are reactivated and produce disease in immunosuppressed patients such as bone marrow and organ transplant recipients (38,55), MBV is a promising agent with a dual potential.…”

mentioning

confidence: 99%

Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication

Wang

Roy

Gershburg

et al. 2009

J Virol

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“…If CMV prophylaxis is interrupted, HSV prophylaxis should be instituted. Successful oral regimens for HSV prophylaxis include acyclovir (34,(54)(55)(56), valacyclovir (58-61) and famciclovir (62,63). Examples of regimens are provided in Table 1.…”

Section: Hsv Preventionmentioning

confidence: 99%

“…reactivation resumes fairly promptly when prophylaxis is stopped (54,(64)(65)(66). Longterm pharmacologic prophylaxis of VZV has not been considered feasible or recommended for these reasons (62). However, acyclovir prophylaxis has been used without significant toxicity for up to 1 year in stem cell recipients (66) and indefinitely in patients with frequent recurrences of genital herpes (67).…”

Section: Vzv Preventionmentioning

confidence: 99%

Herpes Simplex and Varicella Zoster Viruses: Forgotten but Not Gone

Miller

Dummer

2007

American Journal of Transplantation

103

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Herpesvirus infections are common complications of organ transplantation. The most frequent herpesvirus infections are caused by cytomegalovirus (CMV), herpes simplex (HSV) and varicella zoster (VZV). Despite expansion of the therapeutic armamentarium, HSV and VZV continue to cause morbidity and occasional mortality in transplant recipients. Here we review the incidence and risk factors for HSV and VZV disease, their clinical presentation, effects of newer immunosuppressive regimens and prophylaxis for HSV and VZV in solid organ transplant recipients.

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“…In stem-cell and organ transplant recipients, EBV infection poses the hazard of generating B-cell lymphomas that are ultimately fatal. While no drugs are currently approved for treatment of EBV disease, several that inhibit EBV are available, and these can be divided into two main classes: those that target the viral DNA polymerase and those that function independently of it (8)(9)(10)(11)(12). Acyclic nucleoside and phosphonated nucleotide analogs, as well as pyrophosphate analogs, all target the viral polymerase.…”

mentioning

confidence: 99%

Maribavir Inhibits Epstein-Barr Virus Transcription through the EBV Protein Kinase

Whitehurst

Sanders

Law

et al. 2013

J Virol

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A lthough a number of antiviral drugs are effective inhibitors of Epstein-Barr virus (EBV) replication and are used empirically, none is of proven effectiveness for treatment of EBV infection (1, 2). Maribavir (MBV), which is in late-stage clinical trials for use against human cytomegalovirus (HCMV) infection in allogeneic stem cell and bone-marrow transplant recipients (3,4), is of special interest because it is also a potent inhibitor of EBV replication (5-7). In stem-cell and organ transplant recipients, EBV infection poses the hazard of generating B-cell lymphomas that are ultimately fatal. While no drugs are currently approved for treatment of EBV disease, several that inhibit EBV are available, and these can be divided into two main classes: those that target the viral DNA polymerase and those that function independently of it (8-12). Acyclic nucleoside and phosphonated nucleotide analogs, as well as pyrophosphate analogs, all target the viral polymerase.A new class of HCMV inhibitors, benzimidazole compounds, with more specific antiviral properties and fewer adverse side effects, blocked HCMV DNA maturation and encapsidation processes and led to the design of 1-H-␤-L-ribofuranoside-2-isopropylamino-5,6-dichlorobenzimidazole (maribavir [MBV]) (13)(14)(15)(16)(17)(18)(19)(20). Unlike its parent compound, which inhibits HCMV replication but not EBV replication, MBV inhibits both (7,21). Inhibitory effects of MBV are produced mainly through inhibition of the HCMV and EBV protein kinases (PK) (21-24). Previous phase 3 studies with a dosage of 100 mg twice a day (BID) did not have sufficient activity to prevent HCMV disease, but the safety profile and data from case studies suggested that higher doses would be clinically active (3). MBV is now in new phase 2 trials at doses of 400, 800, and 1,200 mg BID (3).Maribavir selectively inhibits the HCMV protein kinase, UL97, determined by direct inhibition of kinase activity in vitro and by genetic mapping of the MBV-resistant phenotype (21). MBV also inhibits the EBV protein kinase (BGLF4), resulting in inhibition of phosphorylation of the EBV DNA processivity factor BMRF1, but does not seem to act directly on the EBV kinase in vitro (7,24).We have recently found that MBV also inhibits expression of multiple EBV transcripts, in contrast to acyclovir (ACV), which has little effect on EBV RNAs. Thus, MBV has a unique dual effect on viral DNA transcription as well as replication (25). In this study, we find that the inhibitory profile of MBV transcripts is similar to that produced by mutant EBV in which PK expression and activity have been knocked out (26). Thus, the results suggest that MBV largely affects EBV transcript levels through inhibition of BGLF4.To determine if the profile of viral transcripts produced by MBV is mediated by the viral kinase, we utilized BGLF4 knockout (KO) (dBGLF4/NeoST) and revertant (dBGLF4/NeoSt/R) viruses constructed and characterized by Murata et al. (26). 293 cells maintaining wild-type (WT), BGLF4 knockout, and revertant EBV genomes (2...

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Viral Prophylaxis in Organ Transplant Patients

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 10 publications

References 1 publication

Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication

Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication

Herpes Simplex and Varicella Zoster Viruses: Forgotten but Not Gone

Maribavir Inhibits Epstein-Barr Virus Transcription through the EBV Protein Kinase

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