Article In addition, this virus is associated with genital herpes, conjunctivitis, keratitis, encephalitis, and eczema herpeticum. Pitcher plant taken by mouth has been used in alternative medicine to treat constipation, urinary tract problems, digestion problems, fluid retention, and other conditions. You can download a PDF version for your personal record. Cells were harvested at 16h.p.i., lysed, separated by SDS-PAGE analyzed by Western blot with antibodies to HSV-1 ICP4, ICP8, gC and cellular actin. HSV-1 is also associated with more severe infections in neonates, elderly people, patients with acquired immune deficiency syndrome, and patients with drug-induced immune suppression. Pitcher plant is a plant. Sci. The Purpurea Sarrecenia Extract seems to Stop you from getting Sick around them in the First Place. Extracts from the carnivorous pitcher plant, Sarracenia purpurea, have previously been shown to inhibit the replication of HSV-1. Oh yes, this is a very slick little plant. Saifulazmi NF, Rohani ER, Harun S, Bunawan H, Hamezah HS, Nor Muhammad NA, Azizan KA, Ahmed QU, Fakurazi S, Mediani A, Sarian MN. official website and that any information you provide is encrypted High affinity gD then binds to the receptors, nectin-1, nectin-2, HVEM, or 3-O-sulphated heparan sulfate, inducing a conformational change and initiating membrane fusion through interaction with the gB and gH/gL complex45,46,47,48,49. Oral. 3A, incubation of HSV-1 with S. purpurea extract during the viral-cell attachment phase inhibited viral plaque formation suggesting that the extract inhibited viral binding to the host cell. RxList does not provide medical advice, diagnosis or treatment. Other drugs are being developed against smallpox, butS. purpurea is the only known therapy that will target the virus at this point in the replication cycle, says Langland. Montvale:Medical Economics, 1999:1289. Statistical analysis was performed using a paired t-test. Preliminary evidence for inhibitory effect of glycyrrhizin on HIV replication in patients with AIDS. 1E). To begin deciphering the mechanism of action of S. purpurea inhibition of HSV-1 replication, the extract was added to a viral single-cycle growth experiment at varying times post-infection. Med. Botanical name: Sarracenia purpurea Preparation.Prepare a tincture from the fresh root, in the proportion of viij. Store at room temperature away from moisture and heat. The immediate-early genes are typically involved in controlling host cell function, for example, ICP4 plays a significant role in the inhibition of host gene transcription. The late proteins form the capsid and the receptors on the surface of the virus. Registered charity number: 207890, Chemical chainmail constructed from interlocked coordination polymers, Battery assembly robot brings factory consistency to the lab, Air quality study highlights nitrogen dioxide pollution in rural India, Welcome to the Inspiring Science collection. Andrei, G. et al. There is much scepticism on herbal medicine but what our results illustrate conclusively is that this herb is able to kill the virus and we can actually demonstrate how it kills the virus, says Langland. Antimicrob. Chatis, P. A., Miller, C. H., Shrager, L. E. & Crumpaker, C. S. Successful treatment with foscarnet of an acyclovir resistant mucocutaneus infection with herpes simplex virus in a patient with acquired immunodeficiency syndrome. 320, 297300 (1989). An official website of the United States government. The active constituent(s) in M. officinalis is caffeic acid and/or its derivatives58. After 24h, the viral yield was determined. Nakabayashi, J. Oral Surg. The injectable form of pitcher plant may cause a sensation of warmth where it is injected into the body. Vero cells were mock infected or infected with HSV-1 at a MOI=5 in the presence or absence of S. purpurea (40g/ml) added at 0, 1, 2, 4, and 6h.p.i. 4) could be due to an inhibition of viral transcription. To quantitate this anti-HSV-1 effect, a plaque reduction assay was performed. Drugs. CAS Eight to twenty-four inch perennial with red-veined leaves. It is not known whether pitcher plant passes into breast milk or if it could harm a nursing baby. Cell Host Microbe. The pelleted virus was washed and titered by a standard plaque formation assay. Sarapin is a grandfathered FDA-approved prescription product. MATH Google Scholar. Epub 2021 Jun 29. & Yao, W. Rhus chinensis and Galla Chinensisfolklore to modern evidence: Review. Sarracenia purpurea has few reliable indications, but many homeopaths report great success in severe cases. Sucrose/Lactose. Statistical analysis was performed using a paired t-test. Extracts from the carnivorous pitcher plant, Sarracenia purpurea, have previously been shown to inhibit the replication of HSV-1. If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password The side effects of pitcher plant taken by mouth are not known. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. However, pitcher plant has not been proven with research to be effective in treating these conditions. Ric Scalzo Institute for Botanical Research, Southwest College of Naturopathic Medicine and Health Sciences, Tempe, AZ, 85282, USA, Biodesign Institute, Arizona State University, Tempe, AZ, 85287, USA, Ashok Kumar,Aradhana Kumar,Bertram Jacobs&Jeffrey Langland, College of Health Solutions, Arizona State University, Phoenix, AZ, 85004, USA, You can also search for this author in MacLeod, D. T., Nakatsuji, T., Yamasaki, K., Kobzik, L. & Gallo, R. L. HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection. Your Cervix Just has a Cold (Gowey Research Group, PLLC, Flagstaff, 2012). Compounds extracted from Sarracenia purpurea include phenolic glycosides, flavonoid glycosides, and iridoids. Oral Med. L.K., As.K., Ar.K. The effect of S. purpurea extracts on VACV replication. PLoS ONE 8, e62482 (2013). The monolayers were washed three times to remove the S. purpurea extract. 1 and34). USA 101, 74457450 (2004). It is not known whether pitcher plant will harm an unborn baby. No cell toxicity was observed with S. purpurea extracts at the doses used (up to 120g/ml) (Fig. Jassim, S. A. To obtain J. Virol. All plant material was subsequently verified by qualified botanical specialists using reference keys. Samples were separated on 10% polyacrylamide gels, transferred to nitrocellulose membrane in blotting transfer buffer (10mM CAPS buffer pH 11.0, 20% methanol) and blocked with 25mM Tris, pH 7.5, 137mM NaCl, 2.5mM KCl, 0.025% Tween, 5% powdered milk. To further confirm the anti-HSV-1 activity of S. purpurea, a single-step growth curve experiment was performed. 2021 Aug 11;29(8):1266-1276.e5. J. Virol. Antivir. Dis. Information not dated. 48, 199226 (1994). Nat. During initial infection, the viral DNA is transported to the spinal cord sensory ganglion through axon transport and latency is established. J. Virol. After 3days, the cell monolayers were stained with crystal violet. Using different formulations together increases the risk of an overdose. J. Drug class: Herbal products. The difference in output viral titers between treatment at 0 and 0.5h.p.i. Version: 1.06. 100% EFFECTIVE! 2015 May;117:115-21. doi: 10.1016/j.antiviral.2015.02.007. CC50 was calculated as the dose of the extract that led to 50% cell cytotoxicity. Vaccinia virus E3 prevents sensing of Z-RNA to block ZBP1-dependent necroptosis. PubMed PubMed was the principal investigator for the study. 5). Adv. Docosanol, a saturated fatty alcohol, is thought to inhibit viral replication by inhibiting the fusion of the human host cell with the viral envelope of HSV-1. 24, 41444153 (2005). Kannan, L., Kumar, A., Kumar, A. et al. To confirm and further characterize that S. purpurea extracts could inhibit HSV-1 replication, Vero cells infected with HSV-1 or uninfected were treated in the presence or absence of S. purpurea extracts and monitored for cytopathic effect (CPE). Figure 5. The team made extracts ofS. purpurea and found that it was highly effective at inhibiting the replication of the virus in rabbit kidney cells. 188, 200203 (2016). The results from Fig. (detailed description of each of the ratings). & Garnett, G. P. A systematic review of the epidemiology and interaction of herpes simplex virus types 1 and 2. Life (Basel). Phytochemistry 94, 238242 (2013). In addition, treatment with S. purpurea extract alone did not induce any noticeable cell toxicity (Fig. Epub 2021 Nov 27. Information about your use of this website will be shared with Google and other third parties. Article The pre-treated monolayers were infected with 200pfu HSV-1-KOS for 1h, cells were washed two times with PBS to remove unbound virus, followed by the addition of complete media, and the cells incubated for 3days at 37C and crystal violet staining to visualize plaque formation. Biol. But that is just because it is small---do not be deceived, for this is a very complicated and subtle plant. Botanical inhibitors of SARS-CoV-2 viral entry: a phylogenetic perspective, Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex, Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro, Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease, In vitro Studies on The Inhibition of Replication of Zika and Chikungunya Viruses by Dolastane Isolated from Seaweed Canistrocarpus cervicornis, Persimmon-derived tannin has antiviral effects and reduces the severity of infection and transmission of SARS-CoV-2 in a Syrian hamster model, In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea, Natural extracts, honey, and propolis as human norovirus inhibitors, Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice, https://doi.org/10.1371/journal.pone.0140765, http://creativecommons.org/licenses/by/4.0/. Suburban Pioneer Posts: 337 November 2021 edited November 2021 Chatter on the street is that smallpox may be the next epidemic. Lancet 2, 764766 (1988). Gupta, R., Warren, T. & Wald, A. 329, 17771782 (1993). J. Med. Article Careers. Med. Furthermore, it is clearly the most successful of all the Sarracenia in that its range is vast compared to its congeners. 1E). 5). Muhammad, A., Haddad, P. S., Durst, T. & Arnason, J. T. Phytochemical constituents of Sarracenia purpurea L. (pitcher plant). This study also demonstrated that S. purpurea extracts have broad antiviral activity and inhibit the replication of HSV-1. Flowers present May through July. These results agree with the temporal synthesis of these proteins, where depending on the cell line, immediate-early protein synthesis begins by 30min post-infection, early protein synthesis begins around 23h.p.i and late protein synthesis begins around 68h.p.i.54,55. Antiviral Res. Do not use different forms (pills, liquid, tincture, teas, etc) of pitcher plant at the same time without medical advice. (E) Vero cells were infected with HSV-1 at a MOI=5 and treated with 0, 20, 40, or 60g/ml of S. purpurea extract. 3, 107121 (2008). These results support the broader anti-viral activity of S. purpurea extracts against both pox and herpes viruses. Do not use this product without medical advice if you are pregnant. Google Scholar. A pitcher plant extract (Sarapin) is given as a shot. Children: 1/2 dose. Federal government websites often end in .gov or .mil. 4 were likely associated with the S. purpurea extract inhibiting HSV-1 immediate-early, early and late viral gene expression. Google Scholar. The effectiveness of these drugs, however, are limited in immune-suppressed patients, resulting in increased likelihood of the virus to develop drug resistance9,10. Perspect. Trost LC, Rose ML, Khouri J, Keilholz L, Long J, Godin SJ, Foster SA. Google Scholar. At 16h.p.i., cells were washed two times with PBS and lysed with 1X SDS sample buffer [125mM TrisCl, pH 6.8, 25% glycerol, 2.5% SDS, 100mM -mercaptoethanol, 0.025% bromophenol blue, 10% protease inhibitor cocktail (ThermoScientific)] and heated for 10min at 95C. Nicola, A. V. & Straus, S. E. Cellular and viral requirements for rapid endocytic entry of herpes simplex virus. In this study, we demonstrate that S. purpurea extracts can inhibit the replication of HSV-1 by two distinct mechanisms of action. For the early protein, ICP8, addition of the extract even at 2h.p.i. Dis. Topics . 26, 423438 (1995). These extracts contain an active constituent which binds to the HSV-1 surface gB thereby inhibiting interaction with the host cell receptor. The https:// ensures that you are connecting to the A. This is not a complete list of side effects and others may occur. Whether you are treated by a medical doctor or a practitioner trained in the use of natural medicines/supplements, make sure all your healthcare providers know about all of your medical conditions and treatments. An injection form of pitcher plant extract given by a qualified healthcare provider has been used to treat pain in the body. J. Virol. Mechanism of action of poxvirus. Provided by the Springer Nature SharedIt content-sharing initiative. & Bryson, H. M. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Historically, several plants have been used in traditional-medicine to effective treat HSV-1 infection22,23,24,25,26,27,28,29,30,31,32,33. PubMed Sarracenia purpurea is an evergreen Perennial growing to 0.3 m (1ft) by 0.3 m (1ft in) at a medium rate. Do not give any herbal/health supplement to a child without medical advice. Pitcher plant injections can cause some side effects including feelings of heat or heaviness. Sarracenia purpurea to the rescue! 4, 1963 (2013). Adv. A. 3C). Repeat at greater intervals as condition subsides. In vitro characterization of a nineteenth-century therapy for smallpox. ADS We use a state-of-the-art microprocessor. Anti-herpes simplex virus activities of monogalactosyl diglyceride and digalactosyl diglyceride from Clinacanthus nutans, a traditional Thai herbal medicine. 88, 96249632 (2014). 85, 283287 (2003). Taylor, T. J., Brockman, M. A., McNamee, E. E. & Knipe, D. M. Herpes simplex virus. Before using pitcher plant, talk to your healthcare provider. PubMed Detection was performed using goat anti-mouse or anti-rabbit IgG secondary conjugated to horseradish peroxidase (Santa Cruz) in the presence of a chemiluminescent substrate (ThermoFisher). At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. Untreated HSV-1 infection gave an approximate 4-log increase in viral titer compared to the input virus (1h.p.i.) https://doi.org/10.1038/s41598-020-76151-w, DOI: https://doi.org/10.1038/s41598-020-76151-w. and titered. 84, 847858 (2006). Pitcher plant is taken by mouth for digestive disorders, particularly constipation; for urinary tract diseases and fluid retention; as a cure for smallpox; and to prevent scar formation. A pitcher plant extract (Sarapin) is given as a shot. Since previous work using S. purpurea extracts against poxviruses demonstrated that the extract did not disrupt the poxvirus envelope34, we propose that the extract is likely blocking HSV-1 attachment to the cell, although further studies to confirm this are required. Acyclovir, a guanine nucleoside analog, competitively targets the viral DNA polymerase, resulting in chain termination and preventing viral DNA elongation8. Written by Cerner Multum. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. CAS The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola . 95, 412427 (2003). Therefore, finding novel anti-herpes compounds is of critical interest. Our lab has previously shown that extracts from S. purpurea can inhibit viral transcription of poxviruses34. Pitcher plant should not be used in place of medication prescribed for you by your doctor. Pathol. Pitcher plant is taken by mouth for digestive disorders, particularly constipation; for urinary tract diseases and fluid retention; as a cure for smallpox; and to prevent scar formation. If you are unable to import citations, please contact National Library of Medicine J. Ethnopharmacol. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Chemotherapy 58, 7077 (2012). At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. Or as directed bya lic. The entire aerial portion/pitcher of the plant was dried (at room temperature for 5days) and then ground to a fine powder in a VitaMix blender. Silica is a leading remedy for severe, chronic cases. 1862;80:615616. & Spear, P. G. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. https://doi.org/10.1371/journal.pone.0140765 (2015). Although, natural smallpox no longer poses a health threat, there is a remote possibility thatunstable states or terrorist groups could have acquiredstocks of the virusfollowing the collapse of the Soviet Union, which had developed smallpox as a biological warfare agent. Lancet 370, 21272137 (2007). The extracts directly inhibit extracellular virions or viral attachment to the host cell as well as inhibiting the expression of ICP4, ICP8 and gC when added at various times post-infection. The .gov means its official. 1C,D). Honess, R. W. & Roizman, B. Error bars indicate the standard deviation from three separate analyses. On some cases of small-pox treated by the Sarracenia purpurea. Following incubation, the virus was pelleted by centrifugation at 20,000g for 1h, washed with media, and resuspended in complete media. Since S. purpurea extracts inhibited HSV-1 replication when added at the time of infection and the reduction in viral titers were below that of input virus (Fig. Before 2022 Aug 22;12(8):1287. doi: 10.3390/life12081287. You may also consider consulting a practitioner who is trained in the use of herbal/health supplements. document.write(new Date().getFullYear()); Kress H Henriette's Herbal Homepage website. Antivir. Commun. Epub 2012 Feb 18. Plants such as Sarracenia purpurea (S. purpurea), Melissa officinalis, Clinacanthus nutans, Glycyrrhiza glabra, Rhus chinensis, Rhus javanica, and Punica granatum have been reported to contain anti-herpetic activity22,23,24,25,26,27,28,29,30,31,32,33. 207, 12951305 (2013). Acad. Biomed. Morrison, S. A., Li, H., Webster, D., Johnson, J. To link your comment to your profile, sign in now. Vero cells were infected with 100200 (plaque forming units) pfu of HSV-1 KOS in the presence of increasing concentrations of S. purpurea or vehicle (50% ethanol, 10% glycerin) for 1h at 37C followed by incubation in media containing S. purpurea or vehicle (50% ethanol, 10% glycerin) for 3days at 37C. Highly Recommended. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. 2012 Apr;94(1):44-53. doi: 10.1016/j.antiviral.2012.02.005. Res. See how this site uses. All Natural! See above for USDA hardiness. Br. Clipboard, Search History, and several other advanced features are temporarily unavailable. CAS Isolation of the active constituents present in S. purpurea may provide future pharmaceutical therapies for HSV-1, and potentially other, herpes virus outbreaks. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. Limited studies support the therapeutic value of S. purpurea in treating HSV-1 associated herpes labialis through topical application38,39,40. Smallpox was an often-fatal diseased cause by infection of human beings by the pox virus variola. Cells were incubated at 37C, with 5% CO2 in a humidified chamber. Cell pre-treatment was performed by treating Vero cell monolayers with increasing concentrations of S. purpurea for 1h at 37C. Antiviral Res. This plant has been used in traditional medicine for a wide variety of medical illnesses, including smallpox infection, gynecological problems, diabetic problems, mycobacterial infection, and liver/kidney complaints34,35,36,37. PubMed Central Available. Cite this article. Shim, Y. J., Doo, H. K., Ahn, S. Y., Kim, Y. S. & Seong, J. K. Inhibitory effect of aqueous extract from the gall of Rhus chinensis on alpha-glucosidase activity and postprandial blood glucose. Headache (including migraine) Pain (neurology) . Copyright 1996-2023 Cerner Multum, Inc. It takes this herb out of the realm of folklore, and into the area of true scientific evidence.. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. sharing sensitive information, make sure youre on a federal In vitro efficacy of brincidofovir against variola virus. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. We are in the process of doing animal studies to confirm our results in at least this type of whole animal system., W Arndt, PLoS One, 2012, DOI: 10.1371/journal.pone.0032610, Advanced designs could transform x-ray science economics, reducing the cost per experiment, Integral metalorganic framework could let wood in construction sequester greenhouse gas, Negotiations over research collaboration to begin immediately when Windsor Framework is signed off, Royal Society of Chemistry The extract blocks early transcription appearing to have a distinct mechanism of action from that of two other antivirals currently in clinical trials, says Mark Buller, a virologist at Saint Louis University, Missouri, US. Sarapin is a grandfathered FDA-approved prescription product. (B) For free virus pre-treatment, 200 pfu of purified HSV-1 virions were treated with 0, 10, 20, 40, or 60g/ml S. purpurea extract and incubated at room temperature for 1h. After incubation the samples were centrifuged at 20,000g for 1h to pellet the virus. Traditional medicinal plants used for treating emerging and re-emerging viral diseases in northern Nigeria. Langland, J. O., Jacobs, B. L., Wagner, C. E., Ruiz, G. & Cahill, T. M. Antiviral activity of metal chelates of caffeic acid and similar compounds towards herpes simplex, VSV-ebola pseudotyped and vaccinia virus. EMBO J. Treatment with S. purpurea gave a dose-dependent reduction in viral titers with an approximate 3-log reduction at 40g/ml and a 4-log reduction at 60g/ml. Generic name: pitcher plant [PITCH-er-plant] Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives. The purple pitcherplant is the only pitcherplant native to New England. Other drugs may interact with pitcher plant, including prescription and over-the-counter medicines, vitamins, and herbal products. may suggest the S. purpurea extract can inhibit HSV-1 replication at two distinct steps in the viral replication process. Article I. Cascade regulation of the synthesis of three groups of viral proteins. These medicinal plants may possess potential anti-herpetic compounds to treat recurrent HSV-1 infection. Disclaimer. & Schnitzler, P. Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro. performed experimental procedures. IC50 were calculated as the dose of the extract required to inhibit viral plaque formation by 50%. Please enable it to take advantage of the complete set of features! Vero cells were treated with S. purpurea or vehicle (50% ethanol, 10% glycerin) at the concentrations indicated. Res. Antimicrob Agents Chemother. Sex Transm. But since the risk is so low for populations at large, it is hard to justify vaccinating everyone, particularly because the vaccine can have serious side effects. Do not use more of this product than is recommended on the label. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. j. to gtts xx. The specificity of S. purpurea. S. purpurea temporal inhibition of HSV-1 replication. Plaques were visualized by staining with 0.1% crystal violet in 20% ethanol. and JavaScript. Please note: your email address is provided to the journal, which may use this information for marketing purposes. Follow all directions on the product label and package. Sarracenia purpurea, commonly known as the purple pitcher plant, northern pitcher plant, turtle socks, or side-saddle flower, is a perennial carnivorous plant in the family Sarraceniaceae. Maxillofac. technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. In addition, these drugs also exhibit side effects including nausea, diarrhea, and vomiting. Samples with statistically significant deviation relative to the 0g/ml S. purpurea treatment are indicated with asterisks (*p<0.05, **p<0.01, ***p<0.005). Djakpo, O. Medicinal use of this product has not been approved by the FDA. As shown in Fig. These results together confirm the anti-HSV-1 activity of S. purpurea extracts. Koehler H, Cotsmire S, Zhang T, Balachandran S, Upton JW, Langland J, Kalman D, Jacobs BL, Mocarski ES. Infect. The work described characterizes the antipoxvirus activity associated with this botanical extract . 55, 14971513 (2003). Injection technique in pain control. B.J. Tell us what you think. (Fig. CAS Astani, A., Reichling, J. Treatment with the extract at various stages during HSV-1 replication cycle resulted in a reduction in viral gene expression and a corresponding reduction in viral protein levels. , P. G. herpes simplex virus, T. & Wald, a single-step growth curve experiment was performed treating. Untreated HSV-1 infection gave an approximate 4-log increase in viral titer compared to the virus. Is transported to the journal, which may use this information for purposes... Infection of human beings by the pox virus variola M. herpes simplex virus groups viral. A traditional Thai herbal medicine immunocompromised patients with AIDS axon transport and latency is established assay performed. Medicine J. Ethnopharmacol J., Brockman, M. A., Li, H. M. a reappraisal of antiviral! Inhibiting interaction with the S. purpurea extracts viral plaque formation by 50 % cytotoxicity.: 10.3390/life12081287 HSV-1 replication at two distinct steps in the replication of HSV-1 in... 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