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      Antiviral Activity of Selected Lamiaceae Essential Oils and Their Monoterpenes Against SARS-Cov-2

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          Abstract

          This study presents the very first report on the in vitro antiviral activity of selected essential oils of Lamiaceae plant species and their monoterpenes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nineteen essential oils were obtained by hydrodistillation of dried plant material, and their monoterpene profiles were determined. In addition, the exact concentrations of each monoterpene that were found at a significant level were defined. Both essential oils and their monoterpene components were tested for cytotoxic and antiviral activity against SARS-CoV-2 in infected Vero 76 cells. The results showed that the essential oils of four Mentha species, i.e., M. aquatica L. cv. Veronica, M. pulegium L., M. microphylla K.Koch, and M. x villosa Huds. , but also Micromeria thymifolia (Scop.) Fritsch and Ziziphora clinopodioides Lam., and five different monoterpenes, i.e., carvacrol, carvone, 1,8-cineol, menthofuran, and pulegone, inhibited the SARS-CoV-2 replication in the infected cells. However, the antiviral activity varied both among essential oils and monoterpenes. Carvone and carvacrol exhibited moderate antiviral activity with IC 50 concentrations of 80.23 ± 6.07 μM and 86.55 ± 12.73 μM, respectively, while the other monoterpenes were less active (IC 50 > 100.00 μM). Structure-activity relations of related monoterpenes showed that the presence of keto and hydroxyl groups is associated with the activity of carvone and carvacrol, respectively. Furthermore, the carvone-rich essential oil of M. x villosa had the greatest activity among all active essential oils (IC 50 127.00 ± 4.63 ppm) while the other active oils exhibited mild (140 ppm < IC 50 < 200 ppm) to weak antiviral activity (IC 50 > 200 ppm). Both essential oils and monoterpenes showed limited or no cytotoxicity against Vero 76 cells. Hierarchical cluster analysis showed that the differences in the antiviral activity of essential oils were directly attributed to the antiviral efficacies of their particular single monoterpenes. The findings presented here on the novel antiviral property of plant essential oils and monoterpenes might be used in the development of different measures against SARS-CoV-2.

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          Most cited references52

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          Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity

          The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread 1,2 . PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host antiviral immune responses 3–5 . Here we perform biochemical, structural and functional characterization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro (SCoV2-PLpro) and outline differences with SARS-CoV PLpro (SCoV-PLpro) in regulation of host interferon and NF-κB pathways. SCoV2-PLpro and SCoV-PLpro share 83% sequence identity but exhibit different host substrate preferences; SCoV2-PLpro preferentially cleaves the ubiquitin-like interferon-stimulated gene 15 protein (ISG15), whereas SCoV-PLpro predominantly targets ubiquitin chains. The crystal structure of SCoV2-PLpro in complex with ISG15 reveals distinctive interactions with the amino-terminal ubiquitin-like domain of ISG15, highlighting the high affinity and specificity of these interactions. Furthermore, upon infection, SCoV2-PLpro contributes to the cleavage of ISG15 from interferon responsive factor 3 (IRF3) and attenuates type I interferon responses. Notably, inhibition of SCoV2-PLpro with GRL-0617 impairs the virus-induced cytopathogenic effect, maintains the antiviral interferon pathway and reduces viral replication in infected cells. These results highlight a potential dual therapeutic strategy in which targeting of SCoV2-PLpro can suppress SARS-CoV-2 infection and promote antiviral immunity.
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            First-wave COVID-19 transmissibility and severity in China outside Hubei after control measures, and second-wave scenario planning: a modelling impact assessment

            Summary Background As of March 18, 2020, 13 415 confirmed cases and 120 deaths related to coronavirus disease 2019 (COVID-19) in mainland China, outside Hubei province—the epicentre of the outbreak—had been reported. Since late January, massive public health interventions have been implemented nationwide to contain the outbreak. We provide an impact assessment of the transmissibility and severity of COVID-19 during the first wave in mainland Chinese locations outside Hubei. Methods We estimated the instantaneous reproduction number (R t) of COVID-19 in Beijing, Shanghai, Shenzhen, Wenzhou, and the ten Chinese provinces that had the highest number of confirmed COVID-19 cases; and the confirmed case-fatality risk (cCFR) in Beijing, Shanghai, Shenzhen, and Wenzhou, and all 31 Chinese provinces. We used a susceptible–infectious–recovered model to show the potential effects of relaxing containment measures after the first wave of infection, in anticipation of a possible second wave. Findings In all selected cities and provinces, the R t decreased substantially since Jan 23, when control measures were implemented, and have since remained below 1. The cCFR outside Hubei was 0·98% (95% CI 0·82–1·16), which was almost five times lower than that in Hubei (5·91%, 5·73–6·09). Relaxing the interventions (resulting in R t >1) when the epidemic size was still small would increase the cumulative case count exponentially as a function of relaxation duration, even if aggressive interventions could subsequently push disease prevalence back to the baseline level. Interpretation The first wave of COVID-19 outside of Hubei has abated because of aggressive non-pharmaceutical interventions. However, given the substantial risk of viral reintroduction, particularly from overseas importation, close monitoring of R t and cCFR is needed to inform strategies against a potential second wave to achieve an optimal balance between health and economic protection. Funding Health and Medical Research Fund, Hong Kong, China.
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              Biological Activities of Essential Oils: From Plant Chemoecology to Traditional Healing Systems

              Essential oils are complex mixtures of hydrocarbons and their oxygenated derivatives arising from two different isoprenoid pathways. Essential oils are produced by glandular trichomes and other secretory structures, specialized secretory tissues mainly diffused onto the surface of plant organs, particularly flowers and leaves, thus exerting a pivotal ecological role in plant. In addition, essential oils have been used, since ancient times, in many different traditional healing systems all over the world, because of their biological activities. Many preclinical studies have documented antimicrobial, antioxidant, anti-inflammatory and anticancer activities of essential oils in a number of cell and animal models, also elucidating their mechanism of action and pharmacological targets, though the paucity of in human studies limits the potential of essential oils as effective and safe phytotherapeutic agents. More well-designed clinical trials are needed in order to ascertain the real efficacy and safety of these plant products.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                02 May 2022
                2022
                02 May 2022
                : 13
                : 893634
                Affiliations
                [1] 1 Centre of the Region Haná for Biotechnological and Agricultural Research , Department of Genetic Resources for Vegetables, Medicinal and Special Plants , Crop Research Institute , Olomouc, Czechia
                [2] 2 Centre of Region Haná for Biotechnological and Agricultural Research , Czech Advanced Technology and Research Institute , Palacky University , Olomouc, Czechia
                [3] 3 Institute of Molecular and Translational Medicine , Faculty of Medicine and Dentistry , Palacky University , Olomouc, Czechia
                [4] 4 Institute of Molecular and Translational Medicine , Czech Advanced Technology and Research Institute , Palacky University , Olomouc, Czechia
                Author notes

                Edited by: Milan Mladenovic, University of Kragujevac, Serbia

                Reviewed by: Vladimir Mihailović, University of Kragujevac, Serbia

                Majid Sharifi-Rad, Zabol University, Iran

                *Correspondence: Sanja Ćavar Zeljković, sanja.cavar@ 123456upol.cz , zeljkovic@ 123456vurv.cz
                [ † ]

                These authors share first authorship

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                893634
                10.3389/fphar.2022.893634
                9108200
                35586050
                7ed5cc0e-83de-4312-80c8-6c665326c097
                Copyright © 2022 Ćavar Zeljković, Schadich, Džubák, Hajdúch and Tarkowski.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 March 2022
                : 14 April 2022
                Funding
                Funded by: Ministerstvo Školství, Mládeže a Tělovýchovy , doi 10.13039/501100001823;
                Award ID: CZ.02.1.01/0.0/0.0/16_019/ 0000827
                Funded by: Ministerstvo Zemědělství , doi 10.13039/501100006533;
                Funded by: European Regional Development Fund , doi 10.13039/501100008530;
                Funded by: Univerzita Palackého v Olomouci , doi 10.13039/501100007059;
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                essential oil,monoterpene,carvacrol,carvone,pulegone,antiviral activity,sars-cov-2,1,8-cineol

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