Possibilities Of Prevention And Treatment Of Human Cytomegalovirus Infections Including New Drugs And Compounds With Potential Application

Abstract

Abstract Human Cytomegalovirus (hCMV) or human herpesvirus 5 (HHV5) is one of the most common pathogens. Studies indicate the presence of infection in 60–100% of individuals. The ability to cause asymptomatic, infection and a latency promotes the persistence and spread of the virus. hCMV infection is usually asymptomatic and does not require treatment, but in some cases especially in immunocompromised persons (e.g., transplant recipients, patients with hematological malignancies, untreated HIV infected individuals) symptoms can be serious and life-threatening. The paper presents drugs currently used for treatment or prevention of hCMV infection, as well as the prospect of new treatment options. Currently, ganciclovir or valganciclovir are used as the first-line drugs and foscarnet and cidofovir are used alternatively. These drugs usually allow to control hCMV infections, however, there are important limitations. These include the toxicity and the possibility of the development of resistance, including the cross-resistance to all four drugs because they have a common mechanism of action, inhibition of viral DNA polymerase. Therefore, the creation of new drugs, with different mechanisms of action, lower toxicity and better pharmacokinetic parameters is important. Recently, the new drug, letermovir have been registered. Letermovir acts as hCMV DNA terminase inhibitor and due to the different mechanism of action the drug is active against hCMV strains resistant to DNA polymerase inhibitors, and potentially can act synergistically with them. The other drugs that are in the research stage or clinical studies include: brincidofovir, a cidofovir derivative, maribavir, a competitive inhibitor of ATP, cyclopropavir, a guanosine analog and antiviral peptides. 1. Introduction – epidemiology of hCMV infections and prophylaxis schemes. 2. Drugs approved for use in the prevention and treatment of hCMV infections. 2.1. Nucleoside analogues: ganciclovir and valganciclovir. 2.2. Foscarnet. 2.3. Cidofovir. 2.4. Letermovir. 3. Compounds with potential use in the treatment of hCMV infections. 3.1. Brincidofovir. 3.2. Maribavir. 3.3. Cyclopropavir 3.4. Antiviral peptides. 4. Summary