As Canada Tackles its 7th COVID-19 Wave, Covid-19 research network CoVarr-Net funded 15 New Studies to examine solutions to Omicron and other variants.
Dr. François Jean, lead of Pillar 10: Antiviral Strategies and Antiviral Therapeutics, has been designated Project Lead of “Therapeutic Approaches and Emerging Therapies for SARS-CoV-2 VOCs: Mono or Combination Therapy, Mechanisms, and Antiviral Resistance.” Dr. Natalie Strynadka, a Pillar 10 Deputy, is also part of the $700,000 project, along with Dr. Mel Krajden from UBC/BC CDC and 6 other researchers from across Canada.
Lay Summary of the Project:
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.
The Coronavirus Variants Rapid Response Network (CoVaRR-Net) was created with a $9 million investment by the Canadian Institutes of Health Research at the end of March 2021 as part of the Government of Canada’s Variants of Concern Strategy. It was allocated another $9 million in 2022. It is a network of interdisciplinary researchers from institutions across the country created to address the potential threat of emerging SARS-CoV-2 variants. Its mandate is to coordinate, facilitate, and accelerate rapid response research throughout Canada regarding variants, such as their increased transmissibility, likelihood to cause severe cases of COVID-19, and resistance to vaccines. The Network collaborates with federal and provincial public health decisionmakers and laboratories, as well as other national and international bodies in an effort to reduce virus transmission and keep Canadians safe. The Network is laying the foundations to evolve into an academic pandemic preparedness network that will foster close ties, collaborations, and relationships with public health laboratories, biomanufacturing facilities and hubs, and industry – because everyone’s contribution is critical during a pandemic.