Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis – the special case of molnupiravir

Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses.

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175 Seasonal changes in metabolism in the woodchuck hepatitis virus model affect the toxicity of the antiviral nucleoside analog FEAU

Antiviral Research ◽

10.1016/0166-3542(94)90298-4 ◽

1994 ◽

Vol 23 ◽

pp. 129

Keyword(s):

Seasonal Changes ◽

Hepatitis Virus ◽

Nucleoside Analog ◽

Woodchuck Hepatitis Virus ◽

Virus Model ◽

Antiviral Nucleoside ◽

Model Affect

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195 Analysis of the pharmacokinetics of the antiviral nucleoside analog FEAU in the woodchuck hepatitis virus model using FMAU as an internal standard for HPLC

Antiviral Research ◽

10.1016/0166-3542(93)90573-2 ◽

1993 ◽

Vol 20 ◽

pp. 148

Keyword(s):

Hepatitis Virus ◽

Internal Standard ◽

Nucleoside Analog ◽

Woodchuck Hepatitis Virus ◽

Virus Model ◽

Antiviral Nucleoside

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Extreme self-sacrifice beyond fusion: Moral expansiveness and the special case of allyship

Behavioral and Brain Sciences ◽

10.1017/s0140525x18001620 ◽

2018 ◽

Vol 41 ◽

Cited By ~ 2

Author(s):

Daniel Crimston ◽

Matthew J. Hornsey

Keyword(s):

General Theory ◽

Biological Markers ◽

Natural Environment ◽

Relevant Dimension ◽

Special Case

AbstractAs a general theory of extreme self-sacrifice, Whitehouse's article misses one relevant dimension: people's willingness to fight and die in support of entities not bound by biological markers or ancestral kinship (allyship). We discuss research on moral expansiveness, which highlights individuals’ capacity to self-sacrifice for targets that lie outside traditional in-group markers, including racial out-groups, animals, and the natural environment.

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