CMV

Cytomegalovirus (CMV) is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. There are currently eight species in this genus including the type species, human cytomegalovirus (HCMV, human herpesvirus 5, HHV-5), which is the species that infects humans. Diseases associated with HHV-5 include glandular fever, and pneumonia.

113852-37-2
Cidofovir
113852-37-2
B0084-084507
Cidofovir dihydrate
149394-66-1
B0084-061144
175865-59-5
175865-60-8
Valganciclovir
175865-60-8
176161-24-3
Maribavir
176161-24-3
444805-28-1
CMX 001
444805-28-1
917389-32-3
Letermovir
917389-32-3

Background


Cytomegalovirus (CMV) is a subfamily of Beta Herpesviruses with a molecular weight of approximately 150 × 106. It is a linear double-stranded DNA with a core diameter of 230 nm and an outer core of 110 nm in the telomeric form. Both are collectively referred to as the nucleocapsid. CMV is present in blood, saliva, tears, urine, semen, feces, cervix and vaginal secretions, breast milk, and the like. Viruses can be excreted in milk, saliva, and urine and last for weeks to years. Human cytomegalovirus (HCMV) is the species that commonly infects humans and is the largest virus in herpesvirus family. Genome size of HCMV is 230 to 240 kbp. HCMV genome consists two sets of unique sequences: unique long (UL) and unique short (US). Each is flanked by inverted repeats. The entire genome has 208 open reading frames (ORFs). The transmission of HCMV in vivo is based on its very extensive tropism on cells and tissues. The main target cells are epithelial, endothelial, fibroblast, and peripheral blood leukocytes. HCMV inhibitors are the main choice for the prevention and treatment of HCMV infection.

Ganciclovir is a highly-efficient, low-toxic and selective HCMV inhibitor. It can inhibit the DNA polymeraseand induce one or more cell kinases after entering the host cell, thereby effectively inhibiting the extension of the HCMV DNA strand. Ganciclovir has strong inhibitory activity against HCMV infections and is the first drug approved by the FDA to treat CMV infection. Acyclovir is a synthetic purine nucleoside analog that competes with deoxyribonucleosides for viral thymidine kinase or cellular kinase, thereby inhibiting HCMV DNA synthesis. Valganciclovir is a guanine analog antiviral drug that is a prodrug of ganciclovir and is rapidly converted to ganciclovir by the gastrointestinal tract and hepatic esterase after oral administration. Foscarnet is a pyrophosphamide analog and is a CMV-DNA polymerase inhibitor. It inhibits CMV replication by blocking the GCV-DNA polymerase acceptor site. Foscarnet does not need to be activated (phosphorylated) by thymidine kinase or other kinases and therefore is active against CMV UL97 mutants in vitro and can be used in patients who have failed ganciclovir tolerance or ganciclovir treatment. Cidofovir is a deoxycytidine analog that does not require viral enzyme activation. It is a broad-spectrum viral inhibitor used for HIV, adenovirus, herpes simplex virus, polyoma virus, orthopoxvirus. Cidofovir converts to cidofovir bisphosphate under the action of cellular thymidine kinase, inhibits DNA polymerization of CMV, slows DNA synthesis, and thereby inhibits virus replication. Cidofovir is effective in the treatment of CMV infection in AIDS patients, but its renal toxicity and inability to be taken orally limit its use.

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References:

1. Oriol, M., Agnieszka, W., Stéphanie, B., Nicolas, J., Mueller, C. D., Hans, H.H., Juerg, S., Martin, S., Adrian, E., Christian, G., Isabelle, B., Maja, W., Christoph, B., Alexia, C., Pascal, M., Manuel, P., Pierre-Yves, B., S.T.C.S., (2015) Influence of IFNL3/4 Polymorphisms on the Incidence of Cytomegalovirus Infection After Solid-Organ Transplantation. Journal of Infectious Diseases, 211 (6): 906-914.

2. Lurain, N.S. Sunwen, Chou, S.W. (2010) Antiviral Drug Resistance of Human Cytomegalovirus. Clinical Microbiology Reviews, 23 (4): 689–712.