A single-administration therapeutic interfering particle reduces SARS-CoV-2 viral shedding and pathogenesis in hamsters

The high transmissibility of SARS-CoV-2 is a primary driver of the COVID-19 pandemic. While existing interventions prevent severe disease, they exhibit mixed efficacy in preventing transmission, presumably due to their limited antiviral effects in the respiratory mucosa, whereas interventions target...

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Bibliographic Details
Published in:bioRxiv 2022-08
Main Authors: Chaturvedi, Sonali, Beutler, Nathan, Pablo, Michael, Vasen, Gustavo, Chen, Xinyue, Calia, Giuliana, Buie, Lauren, Rodick, Robert, Smith, Davey, Rogers, Thomas, Weinberger, Leor
Format: Article
Language:English
Subjects:
COVID-19
Cytokines
Disease resistance
Inflammation
Microbiology
Patent applications
Replication
Severe acute respiratory syndrome coronavirus 2
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Summary:The high transmissibility of SARS-CoV-2 is a primary driver of the COVID-19 pandemic. While existing interventions prevent severe disease, they exhibit mixed efficacy in preventing transmission, presumably due to their limited antiviral effects in the respiratory mucosa, whereas interventions targeting the sites of viral replication might more effectively limit respiratory virus transmission. Recently, intranasally administered RNA-based therapeutic interfering particles (TIPs) were reported to suppress SARS-CoV-2 replication, exhibit a high barrier to resistance, and prevent serious disease in hamsters. Since TIPs intrinsically target the tissues with the highest viral replication burden (i.e., respiratory tissues for SARS-CoV-2), we tested the potential of TIP intervention to reduce SARS-CoV-2 shedding. Here, we report that a single, post-exposure TIP dose lowers SARS-CoV-2 nasal shedding and at 5 days post-infection infectious virus shed is below detection limits in 4 out of 5 infected animals. Furthermore, TIPs reduce shedding of Delta variant or WA-1 from infected to uninfected hamsters. Co-housed contact animals exposed to infected, TIP-treated, animals exhibited significantly lower viral loads, reduced inflammatory cytokines, no severe lung pathology, and shortened shedding duration compared to animals co-housed with untreated infected animals. TIPs may represent an effective countermeasure to limit SARS-CoV-2 transmission. Competing Interest Statement L.S.W., S.C., and R.R. are co-inventors on a patent application filed for therapeutic interfering particles for SARS-CoV-2. L.S.W. is a scientific co-founder of VxBiosciences.
ISSN:2692-8205
DOI:10.1101/2022.08.10.503534