An Update on Current Antiviral Strategies to Combat Human Cytomegalovirus Infection

Abstract

Human cytomegalovirus (HCMV) remains an essential global concern due to its distinct life cycle, mutations and latency. As HCMV is a herpesvirus, it establishes a lifelong persistence in the host through a chronic state of infection. Immunocompromised individuals are at risk of significant morbidity and mortality from the virus. Until now, no effective vaccine has been developed to combat HCMV infection. Only a few antivirals targeting the different stages of the virus lifecycle and viral enzymes are licensed to manage the infection. Therefore, there is an urgent need to find alternate strategies to combat the infection and manage drug resistance. This review will provide an insight into the clinical and preclinical antiviral approaches, including HCMV antiviral drugs and nucleic acid-based therapeutics.

Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers

“…As a general achievement in drug development and targeting options for antiherpesviral treatment, new paths have been opened up [ 5 ]: classically, nucleoside analogs (such as ACV, VACV, GCV, VGCV, FAM, PCV, BVD), nucleoside phosphonate analogs (CDV, BCDV) and pyrophosphate analogs (FOS) have been widely used as viral polymerase inhibitors in antiherpesviral therapies. Recently, mechanistically different targets of HCMV replication, namely viral terminase and viral protein kinase, led to the clinical approval of additional drugs (LMV, MBV) urgently needed in clinical situations [ 7 , 46 ]. At present, a specific focus is given to the potential of herpesviral helicase-primase inhibitors amenamevir (approved for herpes zoster treatment [ 47 , 48 ]) and pritelivir (in clinical phase III [ 49 ]).…”

Human Cytomegalovirus (HCMV) Genetic Diversity, Drug Resistance Testing and Prevalence of the Resistance Mutations: A Literature Review

“…An alternative approach is to target a host cell protein or pathway that is essential for the completion of viral replication. While there is reasonable concern about the possible toxicity of this mechanism of treatment, it would reduce the possibility of the development of drug resistance [ 47 , 48 ].…”

“…It is necessary to read more than 2000 base pairs for the UL54 gene and about 1000 for the UL97 gene to detect resistance to GCV, VGV, CDV and FOS [ 46 , 51 , 52 ]. Fragments of 2100 base pairs of the UL56 gene and 800 base pairs of the UL89 gene need to be sequenced to determine resistance to LMV [ 48 ]. Resistance mutations to MBV are mostly covered with a nucleotide sequence of the UL97 gene; however, for complete resistance testing, sequencing of the UL27 gene is also required [ 35 , 50 ].…”

Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection

“…Human cytomegalovirus (HCMV) infection is highly prevalent worldwide [1], being a major cause of morbidity and mortality among immunocompromised patients, such as AIDS patients or transplant recipients [2]. Currently, antiviral drugs used in the treatment of patients with HCMV infection have low oral bioavailability and dose-related toxicities, such as bone marrow suppression, hepatotoxicity and nephrotoxicity [3]. As a result, there is a great need for the development of alternative treatment options against HCMV [4,5].…”