Abstract
Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species (ROS) that can inactivate microorganisms. The botanical extract PhytoQuinTM is a powerful photosensitizer with antimicrobial properties. We previously demonstrated that photoactivated PhytoQuin also has antiviral properties against herpes simplex viruses and adenoviruses in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. Here, we report that human coronaviruses (HCoVs) are also susceptible to photodynamic inactivation. Photoactivated-PhytoQuin inhibited the replication of the alphacoronavirus HCoV-229E and the betacoronavirus HCoV-OC43 in cultured cells across a range of sub-cytotoxic doses. This antiviral effect was light-dependent, as we observed minimal antiviral effect of PhytoQuin in the absence of photoactivation. Using RNase protection assays, we observed that PDI disrupted HCoV particle integrity allowing for the digestion of viral RNA by exogenous ribonucleases. Using lentiviruses pseudotyped with the SARS-CoV-2 Spike (S) protein, we once again observed a strong, light-dependent antiviral effect of PhytoQuin, which prevented S-mediated entry into human cells. We also observed that PhytoQuin PDI altered S protein electrophoretic mobility. The PhytoQuin constituent emodin displayed equivalent light-dependent antiviral activity to PhytoQuin in matched-dose experiments, indicating that it plays a central role in PhytoQuin PDI against CoVs. Together, these findings demonstrate that HCoV lipid envelopes and proteins are damaged by PhytoQuin PDI and expands the list of susceptible viruses.
Highlights
Coronaviruses (CoVs) are enveloped viruses with large positive-sense, single-strandedRNA genomes
For our experiments to investigate the Photodynamic inactivation (PDI) of human coronaviruses, we employed a PS, PhytoQuin, which is an extract from Polygonum cuspidatum prepared by PhotoDynamic, Inc
We demonstrated that PhytoQuin, a photosensitizing botanical extract, inactivated distantly related human coronaviruses HCoV-229E and HCoVOC43, as well as pseudotyped lentiviruses bearing SARS-CoV-2 S protein
Summary
Coronaviruses (CoVs) are enveloped viruses with large positive-sense, single-strandedRNA genomes. Following uncoating in the cytoplasm, the CoV (+)ssRNA genome is translated into long polyproteins that are processed by viral proteases to yield non-structural proteins, including the viral. RNA-dependent RNA polymerase (RdRp) and associated RNA modifying enzymes [2], as well as an RNA exonuclease enzyme that provides essential proofreading activity to ensure high-fidelity replication of the viral genome [3]. These viral enzymes assemble to form the replicase-transcriptase complex that orchestrates viral transcription and genome replication in discrete cytoplasmic compartments [4]. According to the longstanding model, progeny CoV virions escape the host cell by traversing the secretory pathway, but recent studies of SARS-CoV-2 and the related betacoronavirus mouse hepatitis virus have provided evidence for an alternative lysosomal egress pathway [6]
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