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Antiviral Therapy Update: Antiviral activity of molnupiravir precursor NHC against Variants of Concern (VOCs) and its therapeutic window in a human lung cell model

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eMediNexus    10 February 2022

The UK Medicines and Regulatory Healthcare Agency (MHRA) have newly licensed the anti-viral drug, molnupiravir, for use in patients with mild-moderate COVID-19 disease with one or more risk factors for serious illness. Anti-viral drugs should be initiated at the earliest to prevent progression to severe disease, although the therapeutic window for intervention is yet not clearly described.

A study determined the activity of the molnupiravir (NHC) to different SARS-CoV-2 Variants of Concern (VoCs) and established the therapeutic window in the human lung cell model.

Dose-response assays were done to determine the IC50 (the concentration of drug required to inhibit virus titre by 50%) of NHC against different variants. NHC treated Human ACE-2 A549 cells at different time points were utilized.

The following observations were made-

  • ß-D-N4-hydroxycytidine (NHC) shows identical activity against four variants of SARS-CoV-2 in a human lung cell line ranging 0.04-0.16µM IC50. 
  • In-vitroactivity of the drug is decreased in cells exposed to the drug 48 hours after infection.

 

Thus, Molnupiravir is advantageous as it can be administered orally and thus can be utilized in patients in an outpatient setting. These data suggest that this drug should be given early after diagnosis or even in prophylaxis for individuals with a high risk of developing severe disease.

 

SOURCE- bioRxiv 2021.11.23.469695; doi: https://doi.org/10.1101/2021.11.23.469695

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