Geno- and Phenotypic Characterization of Human Cytomegalovirus Mutants SelectedIn Vitroafter Letermovir (AIC246) Exposure

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Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure.

Letermovir is a novel antiviral compound currently in clinical development for the prevention of human cytomegalovirus (HCMV) infections. In contrast to all currently approved anti-HCMV drugs that target the viral DNA polymerase, letermovir acts via a distinct mode of action involving the viral terminase subunit pUL56. To extend our understanding of potential letermovir resistance mechanisms, w...

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The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.

Human cytomegalovirus (HCMV) remains the leading viral cause of birth defects and life-threatening disease in transplant recipients. All approved antiviral drugs target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Attempts to discover improved anti-HCMV drugs led to the identification of the small-molecular-weight compound AIC246 ...

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In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication.

Despite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues a...

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In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses.

AIC246 (letermovir) is a potent anticytomegalovirus drug in clinical development. Here, we report a consistent antiviral efficacy of AIC246 against human cytomegalovirus laboratory strains, clinical isolates, and virus variants resistant to approved drugs. Furthermore, we describe a remarkable selectivity of AIC246 for human cytomegaloviruses compared to that of other alpha-, beta-, or gammaher...

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Genetic and phenotypic characterization of capsule mutants of Cryptococcus neoformans.

Stable mutants with reduced capacity to produce capsules were isolated from suspensions of Cryptococcus neoformans after treatment of the wild type with a mutagen. The mutants could be assigned one of two phenotypes, hypocapsular or acapsular. Hypocapsular mutants were immunochemically and physicochemically indistinguishable from the wild type, whereas acapsular mutants lacked a major capsular ...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2013

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.01794-13