Key result
A pan-coronavirus CRISPR-CasRx effector system reduced viral titer by 85% to >99% in HCoV-OC43, 78% to >99% in HCoV-229E, and 70% to 94% in SARS-CoV-2 compared with an untreated virus control.
Why the study?
CRISPR-based technology has become widely used as an antiviral strategy, prompting the design and testing of a pan-coronavirus CRISPR-CasRx effector system targeting multiple HCoV species.
A pan-coronavirus CRISPR-CasRx effector system demonstrates proof-of-concept for reducing viable virus across multiple human coronavirus species, including SARS-CoV-2.
Hypothesis-generating for CRISPR pan-coronavirus antivirals in preclinical models; leaves open translation to human therapy.
CRISPR-based technology has become widely used as an antiviral strategy, including as a broad-spectrum human coronavirus (HCoV) therapeutic. In this work, we have designed a CRISPR-CasRx effector system with guide RNAs (gRNAs) that are cross-reactive among several HCoV species. We tested the efficacy of this pan-coronavirus effector system by evaluating the reduction in viral viability associated with different CRISPR targets in HCoV-OC43, HCoV-229E, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We determined that several CRISPR targets significantly reduce viral titer, despite the presence of single nucleotide polymorphisms in the gRNA when compared with a non-targeting, negative control gRNA. CRISPR targets reduced viral titer between 85% and >99% in HCoV-OC43, between 78% and >99% in HCoV-229E, and between 70% and 94% in SARS-CoV-2 when compared with an untreated virus control. These data establish a proof-of-concept for a pan-coronavirus CRISPR effector system that is capable of reducing viable virus in both Risk Group 2 and Risk Group 3 HCoV pathogens.
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Mayes et al. (2023) studied Human coronavirus (HCoV-OC43, HCoV-229E, SARS-CoV-2). pan-coronavirus CRISPR-CasRx effector system vs. untreated virus control and non-targeting negative control gRNA was evaluated on reduction in viral viability/titer. A pan-coronavirus CRISPR-CasRx effector system reduced viral titer by 85% to >99% in HCoV-OC43, 78% to >99% in HCoV-229E, and 70% to 94% in SARS-CoV-2 compared with an untreated virus control.
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