New drug on the horizon for treating adenovirus.
Human adenoviruses can cause serious disseminated infections including death in immunosuppressed patients, especially pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. There are no drugs approved to treat such infections. Cidofovir is used intravenously in many transplant clinics, probably with some effect, but controlled trials have not been completed. Cidofovir is an acyclic nucleoside phosphonate analog of cytidine monophosphate. Following conversion to its diphosphate form within cells, cidofovir is a preferred substrate for the adenovirus DNA polymerase, leading to viral DNA chain termination. Problems with cidofovir include poor cellular uptake and nephrotoxicity. Brincidofovir, a lipid-linked derivative of cidofovir which is active against five families of double-stranded DNA viruses, represents a major advance in anti-adenovirus therapy. It is administered orally, taken up readily by cells followed by release of cidofovir within cells, and is not nephrotoxic. Brincidofovir, under development by Chimerix, Inc., is being evaluated against adenovirus infections in transplant patients including allo-HSCT patients in a phase III clinical trial (AdVise Study). Preliminary results indicate that brincidofovir is safe and very effective at decreasing adenovirus viremia and adenovirus-induced pathogenicity and mortality. Anti-adenovirus adoptive T cell therapy is another very promising approach to treating allo-HSCT patients as demonstrated in clinical studies.
a 1 Saint Louis University School of Medicine, Department of Molecular Microbiology and Immunology , 1100 S. Grand Boulevard, St. Louis, MO, USA +1 314 977 8857 ; +1 314 977 8717 ; woldws@slu.edu.
William S M
WS
Wold
b 2 Saint Louis University School of Medicine, Department of Molecular Microbiology and Immunology , 1100 S. Grand Boulevard, St. Louis, MO, USA.
Karoly
K
Toth
D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000628:therapy; D000260:Adenoviruses, Human; D019264:Adoptive Transfer; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004279:DNA, Viral; D006801:Humans; D016867:Immunocompromised Host; D063065:Organophosphonates / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000637:transplantation
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; C525733:brincidofovir; D003596:Cytosine; D000077404:Cidofovir
Syrian hamster animal model; adenovirus; brincidofovir; cidofovir