Molnupiravir

Molnupiravir

Subject – Science and Tech

Context – ‘Virus less likely to develop resistance to molnupiravir’

Concept –

• The anti-viral drug molnupiravir can reduce risk of hospitalisation or death by 50% in non-hospitalised adult patients with mild-to-moderate COVID-19 disease. That molnupiravir is an oral drug is a major advantage in treating patients as it would not require hospitalisation.
• Molnupiravir is a pro-drug, which means that it needs to undergo processing in the body to become active. It is metabolised to a ribonucleosideanalog, which is essentially a sugar molecule linked to a molecule that resembles a nucleic acid.
• Nucleic acids are needed to make RNA, and if molnupiravir is used, the viral enzyme instead of using real cytidine or uridine uses a molecule that is generated by metabolism of molnupiravir called NHC-TP.
• The virus has a proof-reading mechanism but the viral ex-nuclease which is responsible for removing mistakes does not recognize NHC-TP as an error, so that when the viral RNA polymerase is making copies of RNA that contains molnupiravir, then it randomly replaces cytidine or uridine. This causes more mutations that can be survived by the virus or it becomes unable to replicate — this is called lethal mutagenesis or error catastrophe
• The drug has performed well against influenza in animal studies and was set to go into phase-1 trials in 2020. It has also worked well against Ebola and Chikungunya.
• If multiple antivirals are available then using a combination that targets different steps in the replication of the virus is the best way to delay the development of resistance. Both remdesivir and molnupiravir target the same enzyme but in different ways

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