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Universally available herbal teas based on sage and perilla elicit potent antiviral activity against SARS-CoV-2 variants of concern by HMOX-1 upregulation in human cells

ABSTRACT: The current SARS-CoV-2/COVID-19 pandemic causes medical and socioeconomic havoc. Despite the availability of vaccines, cost-effective treatment options preventing morbidity and mortality are urgently needed. To identify affordable, ubiquitously available, and effective treatments, we tested herbs consumed worldwide as herbal teas regarding their antiviral activity against SARS-CoV-2. Aqueous infusions prepared by boiling leaves of the Lamiaceae perilla and sage elicit potent and sustained antiviral activity against SARS-CoV-2 in therapeutic as well as prophylactic regimens. The herbal infusions exerted antiviral effects comparable to interferon-β and remdesivir but outperformed convalescent sera and interferon-α2 upon short-term treatment early after infection. Based on protein fractionation analyses, we identified caffeic acid, perilla aldehyde, and perilla alcohol as antiviral compounds. Global mass-spectrometry (MS) analyses performed comparatively in two different infection models (Vero E6 and Caco-2 cell lines) revealed changes of the proteome upon treatment with herbal infusions and provided insights into the mode of action. As inferred by the MS data, induction of heme oxygenase 1 (HMOX-1) was confirmed as effector mechanism by the antiviral activity of HMOX-1-inducing compounds sulforaphane and fraxetin. In conclusion, herbal teas based on perilla and sage exhibit antiviral activity against SARS-CoV-2 including the variants of concern Alpha, Beta, Delta, and Omicron.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Chlorocebus Sabaeus

TISSUE(S): Epithelial Cell

DISEASE(S): Covid-19

SUBMITTER: Roman Sakson

LAB HEAD: Albert Sickmann

PROVIDER: PXD030742 | Pride | 2022-10-25

REPOSITORIES: Pride

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			Action	DRS
	210112_RS_crap.fasta	Fasta
	Caco2_PD_Settings.txt	Txt
	Caco2_Protein_Data_and_Plots.xlsx	Xlsx
	Clorocebaus_sabeus_20210113_uniprot-proteome_UP000029965.fasta	Fasta
	Nsp_SARS-CoV-2_20210201_uniprot-proteome_UP000464024.fasta	Fasta

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Project description:Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. We also evalulate the effect of antiviral therapy on host gene expression using RNAseq and show that therapeutic intervention reduces host inflammatory response as compared to vehicle controls during acute SARS-CoV-2 infection. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.

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Universally available herbal teas based on sage and perilla elicit potent antiviral activity against SARS-CoV-2 variants of concern by HMOX-1 upregulation in human cells

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