What question did this study set out to answer?

To characterize the preclinical antiviral potency, resistance profile, and pharmacokinetic behavior of the novel NS3/4a protease inhibitor MK-5172.

May 22, 2012Antimicrobial Agents and ChemotherapyOpen Access

MK-5172, a Selective Inhibitor of Hepatitis C Virus NS3/4a Protease with Broad Activity across Genotypes and Resistant Variants

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Authors

VSVincenzo SummaFederico II University Hospital SLSteven W. LudmererUnited States Military Academy JMJohn A. McCauleyUnited States Military Academy

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Implication

Preclinical study reveals potent pan-genotypic antiviral activity and resistance barrier for MK-5172 in animal models, indicating potential for all-oral hepatitis C therapy.

Key Points

To characterize the preclinical antiviral potency, resistance profile, and pharmacokinetic behavior of the novel NS3/4a protease inhibitor MK-5172.
In vitro evaluation of MK-5172 against an enzyme panel representing major HCV genotypes and protease inhibitor-resistant variants, accompanied by replicon selection assays.
Pharmacokinetic and liver distribution profiling following oral administration in rats and dogs.
In vivo antiviral efficacy testing in chimpanzees chronically infected with HCV genotype 1a or 1b treated with 1 mg/kg twice daily for 7 days.
MK-5172 exhibited subnanomolar enzymatic inhibition across major HCV genotypes and resistance variants, exerting high selective pressure that yielded minimal resistant replicon colonies.
Pharmacokinetic evaluations in rats and dogs demonstrated high plasma and liver exposures, with sustained 24-hour liver drug levels suitable for once-daily dosing.
Treatment in chronically infected chimpanzees produced a 4 to 5 log reduction in viral load across both genotype 1a and genotype 1b infections.

Cite This Study

Summa et al. (2012) studied this question.

synapsesocial.com/papers/69de7d861d9bba5129b0c244 https://doi.org/10.1128/aac.00324-12

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Implication

Preclinical study reveals potent pan-genotypic antiviral activity and resistance barrier for MK-5172 in animal models, indicating potential for all-oral hepatitis C therapy.

MK-5172, a Selective Inhibitor of Hepatitis C Virus NS3/4a Protease with Broad Activity across Genotypes and Resistant Variants

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Implication

Key Points

Cite This Study

MK-5172, a Selective Inhibitor of Hepatitis C Virus NS3/4a Protease with Broad Activity across Genotypes and Resistant Variants

Discussion

Member takes

Implication

Key Points

Cite This Study

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