Year 2 Project
François Jean, University of British Columbia, Lead of Pillar 10: Antiviral Strategies and Antiviral Therapeutics, and Project Lead
Nathalie Grandvaux, Université de Montréal, Pillar 10 Deputy
Ioannis Ragoussis, McGill University, Pillar 5 Lead
Deanna Santer, University of Manitoba, Pillar 10 Deputy
Natalie Strynadka, University of British Columbia, Pillar 10 Deputy
Rob Kozak, Sunnybrook Health Sciences Centre, Pillar 10 Member
Prameet Sheth, Queen’s University, Pillar 10 Member
Joyce Wilson, University of Saskatchewan, Pillar 10 Member
Mel Krajden, BCCDC/University of British Columbia
Antivirals approved by Health Canada, such as Remdesivir and Paxlovid, are playing an increasingly important role in limiting disease severity and death due to COVID-19. It is well known that for other RNA virus infections, such as hepatitis C and influenza A, antiviral resistance has developed when long-term antiviral treatment is used as a monotherapy, rendering a drug ineffective. The development of drug resistance against the few available antivirals against SARS-CoV-2 has not been well studied but the potential for drug resistance to develop is high for a rapidly mutating virus, such as this one. As novel SARS-CoV-2 variants of concern continue to emerge and antiviral use increases, we have identified these priority projects to assess the potential for Omicron variants to develop antiviral resistance mutations against monotherapies and to study promising combination antiviral therapies during Year 2:
- Investigate the capacity for SARS-CoV-2 variants of concern (Omicron BA.2 and BA.5) to develop resistant mutations in cell-based assays and in hospitalized and immunocompromised patients in Canada.
- Use cell-based assays to understand how current antiviral approaches may be improved when combined with leading clinical candidates for novel antivirals targeted at host proteins needed for the virus to enter cells or replicate, and that regulate the host immune response.
- Study and test how detected virus mutations impact the virus’s fitness, susceptibility to antivirals, and how the mutations affect binding of antiviral drugs to their targets at the atomic level, and if they have an impact on innate immune signalling.
This work will provide critical information on the potential for SARS-CoV-2 Omicron variants to resist current antiviral treatments and how combination antiviral therapies can be used as alternatives to monotherapy to improve treatment.
$700,000 cash contribution