Drug susceptibility and the potential for drug-resistant SARS-CoV-2 emergence in immunocompromised animals

Area of Science:

• Virology
• Infectious Diseases
• Pharmacology

Background:

• Omicron variants (e.g., BQ.1.1, XBB) show reduced susceptibility to mRNA vaccines and monoclonal antibodies.
• This necessitates the exploration and validation of effective antiviral therapies.
• Antiviral drug efficacy against emerging variants requires continuous assessment.

Purpose of the Study:

• To evaluate the in vivo efficacy of molnupiravir and nirmatrelvir against the Omicron BQ.1.1 SARS-CoV-2 variant.
• To assess the potential for drug-resistant variant emergence in immunocompromised hosts.

Main Methods:

• Syrian hamsters were used to model SARS-CoV-2 BQ.1.1 infection.
• Molnupiravir and nirmatrelvir were administered prophylactically or therapeutically.
• Viral load in lung tissue was quantified.
• Drug resistance was assessed in viruses isolated from immunocompromised hamsters treated for 13 days.

Main Results:

• Both molnupiravir and nirmatrelvir significantly reduced viral load in hamster lungs.
• Complete viral clearance was not achieved in immunocompromised hamsters after 13 days of treatment.
• No reduced susceptibility to the antivirals was observed in viruses isolated from treated immunocompromised hamsters.
• Limited emergence of drug-resistant variants was noted under the tested conditions.

Conclusions:

• Molnupiravir and nirmatrelvir demonstrate in vivo effectiveness against SARS-CoV-2 variants resistant to vaccine and antibody therapies.
• These antivirals remain viable treatment options, with minimal observed resistance development in the tested models.
• Further research into long-term efficacy and resistance in diverse host conditions is warranted.