HCMV Antivirals and Strategies to Target the Latent Reservoir

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir.

The crystal structure of the varicella-zoster Orf24-Orf27 nuclear egress complex spotlights multiple determinants of herpesvirus subfamily specificity

“…Treatments are also under the continuous threat of the emergence of viral drug resistance or vaccine escape mutations. Hence, the identification of novel antiherpesviral drugs and targeting strategies remains a global research focus ( 10 , 11 ).…”

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

“…It was showed that GCV inhibits EBV; HHV 6, 7, and 8; and hepatitis B virus (HBV) replication, as well. In the clinical practice, it is the drug of choice to treat the CMV infection [ 50 , 51 , 52 , 53 , 54 , 55 ]. GCV is indicated to treat cytomegalovirus retinitis as a suppressive therapy, used for the prevention of CMV disease in transplant recipients.…”

“…GCV is first phosphorylated by the viral protein kinase (encoded by the CMV UL97 gene) and then diphosphorylated by cellular kinases. GCV is an inhibitor of viral DNA polymerase (encoded by the CMV UL54 gene) [ 18 , 50 , 51 ]. When orally administered, it is absorbed in only 5–10%.…”

“…The most needed are new possibilities for the control CMV viremia and prevention of CMV disease in SOT and HSC transplant patients. Recently, the therapeutic options have been expanded to include the new drugs described below, such as letermovir, maribavir, and brincidofovir [ 51 , 52 , 60 ].…”

Strigolactones, from Plants to Human Health: Achievements and Challenges

“…In addition, HCMV infection is the most frequent cause of congenital malformation in developed countries [ 147 ]. Although nucleoside analogues have been successfully used against HCMV, their use is hampered by the occurrence of serious side effects, the rapid emergence of resistance and the fact that their efficacy is limited to alleviating symptoms, without eradicating the latent infection [ 148 , 149 ]. There is, therefore, an urgent clinical need for new antiviral drugs that can overcome these limitations.…”