( 12 ) United States Patent

Home , Amasonia, Collinsonia, Ovieda, Oxera, Tetraclea, Volkameria

US010293012B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 293 ,012 B2 Langland et al. (45 ) Date of Patent: May 21, 2019 (54 ) METHODS OF USING EXTRACTS OF OTHER PUBLICATIONS MELISSA OFFICINALIS AGAINST FILOVIRUSES Chattopadhyay, et al. , Evidence - Based Validation of Herbal Medi cine , Ch . 8 : 175 . ( Year: 2015 ) . * Arndt, W . et al ., “ In Vitro Characterization of a Nineteenth - Century ( 71 ) Applicants : Jeffrey Langland , Chandler, AZ (US ) ; Therapy for Smallpox ” , PLoS One, Mar. 2012 , 7 ( 3 ), article ID Bertram Jacobs, Tempe , AZ (US ) ; e23610 , 9 pages . Karen Denzler , Phoenix , AZ (US ) Astani , A . et al. , “ Melissa officinalis Extract Inhibits Attachment of Herpes Simplex Virus in vitro ” , Chemotherapy, 2012 (published (72 ) Inventors : Jeffrey Langland , Chandler , AZ (US ) ; online Feb . 2012 ) , 58 , pp . 70 - 77 . Chattopadhyay, D . et al ., “ Ethnomedicines and ethnomedicinal Bertram Jacobs, Tempe , AZ (US ) ; phytophores against herpesviruses” , Biotechnology Annual Review , Karen Denzler , Phoenix , AZ (US ) 2008 (available online Jul. 2008 ) , 14 , pp . 297 - 348 . Cheng, C . et al. , “ Recent Advances in the Discovery of Novel ( 73 ) Assignee : Arizona Board of Regents on behalf Anti- Herpetic Agents from Chinese Herbal Medicines ” , Current of Arizona State University , Scotsdale , Organic Chemistry, 2010 , 14 ( 16 ), pp . 1714 - 1726 . AZ (US ) Downing, A . , “ Inter and intra - specific differences in medicinal plant use for the treatment of type II diabetes symptoms by the Cree Elders of Eeyou Istchee ( QC ) ” , University of Montreal, Papyrus ( * ) Notice : Subject to any disclaimer , the term of this Institutional Repository, Master ' s Thesis , 2010 , 117 pages . patent is extended or adjusted under 35 Harris , C . et al ., " Characterizing the cytoprotective activity of U . S .C . 154 (b ) by 0 days . Sarracenia purpurea L ., a medicinal plant that inhibits glucotoxic ity in PC12 cells ” , BMC Complementary and Alternative Medicine , ( 21 ) Appl. No. : 15 /970 ,222 Dec 2012 , 245 , 10 pages , https : // doi. org / 10 . 1186 / 1472 -6882 - 12 245 . (22 ) Filed : May 3 , 2018 Krauze - Baranowska , A . et al. , “ HPLC of flavanones and chalcones in different species and clones of Sali ” , Acta Poloniae Pharmaceutica , Prior Publication Data Jan . 2013 , 70 ( 1 ) , pp . 27 - 34 . (65 ) Patent Cooperation Treaty , International Searching Authority , Inter US 2018 /0318373 A1 Nov . 8 , 2018 national Preliminary Report on Patentability and Written Opinion for PCT/ US2013 /071332 , 12 pages , report dated May 26 , 2015 , opinion dated Apr . 30 , 2014 . Patent Cooperation Treaty , International Searching Authority, Inter Related U . S . Application Data national Search Report for PCT/ US2013 / 071332, 6 pages , dated (60 ) Provisional application No . 62 /501 , 446 , filed on May Apr. 30 , 2014 . 4 , 2017 Patent Cooperation Treaty , International Searching Authority , Inter national Search Report for PCT/ US2018 / 031538 , 4 pages , dated ( 51) Int. Ci. Sep . 17 , 2018 . A61K 36 /53 ( 2006 .01 ) Patent Cooperation Treaty , International Searching Authority , Writ ten Opinion for PCT/ US2018 /031538 , 7 pages , dated Sep . 17 , 2018 . A61P 31/ 14 ( 2006 .01 ) Perfect , M . et al ., “ Use of Complementary and Alternative Medicine (52 ) U .S . Cl. for the Treatment of Genital Herpes” , Herpes , Oct. 2005 , 12 ( 2 ) , pp . CPC ...... A61K 36 / 53 (2013 .01 ) ; A61P 31/ 14 38 -41 . ( 2018 .01 ) ; A61K 2236 /333 ( 2013 .01 ) Salvador, B . et al. , “ Filoviruses Utilize Glycosaminoglycans for (58 ) Field of Classification Search Their Attachment to Target Cells ” , Journal of Virology , Mar . 2013 None ( published ahead of print Jan . 2013 ) , 87 ( 6 ) , pp . 3295 - 3304 . USPTO , Non - Final Office Action for U . S . Appl. No. 14 / 443 ,767 , See application file for complete search history. dated Aug . 1 , 2018 , 8 pages . Wang , Z . et al. , “ High Genetic Diversity in Sarracenia leucophyl (56 ) References Cited la (Sarraceniaceae ) , a Carnivorous Wetland Herb ” , Journal ofHered U .S . PATENT DOCUMENTS ity , May 2004 , 95 ( 3 ) , pp . 234 - 243 . 2005 / 0095260 A1 5 / 2005 Pardoe * cited by examiner 2007 / 0122492 AL 5 / 2007 Behr et al. 2012 / 0141610 A1 6 / 2012 Gowey Primary Examiner — Michael Barker 2018 /0200320 A17 /2018 Langland et al. (74 ) Attorney, Agent, or Firm — Byrne Poh LLP ; Nina R . FOREIGN PATENT DOCUMENTS Horan EP 0249165 A2 12 / 1987 (57 ) ABSTRACT wo 2005074947 A2 8 / 2005 WO 2009048595 A2 4 / 2009 The present disclosure relates to methods of using Melissa WO 2014081976 A1 5 / 2014 officinalis extracts in inhibiting viral replication of a filovirus WO 2016012913 A1 1 / 2016 and in treating or preventing a filovirus infection . WO 2016123223 AL 8 / 2016 WO 2018208739 AL 11 /2018 19 Claims, 8 Drawing Sheets atent May 21, 2019 Sheet 1 of 8 ?? 10, 293 ,012 B2 Melissa extractmlul/18 23 :

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FIG.8A ...... WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW formation plaque Percent US 10 , 293 , 012 B2 METHODS OF USING EXTRACTS OF raphy. After removal of g? binding components present in MELISSA OFFICINALIS AGAINST the Melissa extract , the HSV1 inhibitory activity was greatly FILOVIRUSES reduced ( FIG . 4 ). This result suggests that the active con stituent of Melissa binds to g? of the virion particle . In BACKGROUND 5 summary , these results support that Melissa extracts inhibit herpes virus binding to heparin sulfate on the cell surface by Medicinal plant extracts are of interest as sources ofnovel binding to the HSV1 g? and blocking viral attachment. antiviral agents . Melissa officinalis , commonly known as Cell cytotoxicity is an important concern when consider Lemon Balm , is an abundant botanical historically claimed ing any potential therapeutic . In assays , inhibition of HSV1 ave strong antiviral properties. Melissa has a long 10 virus replication occurred at a low dose ( EC50 = 0 .58 ul/ ml ) medicinal history being used first up to two thousand years (FIG . 5 ) . Upon testing for cell cytotoxicity , the extract did ago by the Greeks . Melissa is purported to help significantly not exhibit detectable cell cytotoxicity with the CC = 0 = 190 in the treatment of herpes simplex viruses, HSV1 and HSV2. The antiviral activity associated with Melissa has utilized ul/ ml being comparable to glycerin (vehicle ) alone. (FIG . 5 ) . glycerine -based extracts prepared from dried Melissa offi - 15 SUMMARY cinalis . The botanical was ground to a fine powder followed by resuspension in 75 % glycerin (pharmaceutical grade , The present disclosure relates to the discovery that organic vegetable glycerin ) at a ratio of 1 : 8 ( dried plant extracts of the botanical Melissa officinalis have antiviral material to extraction solution ). The solution was stored at activity against filoviruses . Accordingly , the present disclo room temperature for seven days followed by removal of the 20 sure provides a method of using Melissa officinalis extracts botanical debris by centrifugation and sterilization through a in inhibiting viral replication of a filovirus . The present 0 . 2 um filter. disclosure also provides a method of using Melissa offici Previous studies have demonstrated that extracts from nalis extracts in treating or preventing a filovirus infection . Melissa officinalis can inhibit the replication of herpes In one embodiment, the filovirus is an Ebola virus . In viruses . As shown in FIG . 1 ( lower left corner ), cells 25 another embodiment , the filovirus is Marburg virus. infected with HSV lead to dramatic cytopathic effects and cell death . As cells were treated with increasing concentra BRIEF DESCRIPTION OF THE FIGURES tions of Melissa extract, a dose dependent reduction in cell death was observed . Uninfected cells (FIG . 1 , upper row ) FIG . 1 shows that Melissa inhibits replication of HSV1 . remained morphologically normal and healthy . 30 FIG . 2 shows that Melissa inhibits binding of HSV to Many different cell surface molecules can serve as recep - heparin agarose , at a dose similar to which it inhibits tors for the attachment and entry of viruses . The particular replication of HSV . receptor or receptors a virus can use will determine the cell FIG . 3 shows that Melissa inhibits HSV1 replication types it can infect. For HSV1, cell surface heparin sulfate when added to the virus , but not when added to cells proteoglycans serve as the cell surface receptor. Previous 35 FIG . 4 shows that anti- HSV1 components in Melissa data demonstrates that cells treated with heparinases or likely bind to the viral glycoprotein B . altered by mutations that prevent heparin sulfate biosynthe - FIG . 5 shows that Melissa has very low toxicity to sis have reduced capabilities to bind HSV1 and are partially uninfected cells . resistant to virus infection . Soluble heparin has been shown FIG . 6 shows that Melissa potently inhibits replication of to competitively inhibit HSV1 infection . Through temporal 40 HSV1, HSV2 and Ebola - VSV , moderately inhibits replica studies, it has been demonstrated that extracts ofMelissa can t ion of VACV, SV40 and Adenovirus , poorly inhibits repli inhibit HSV1 binding to cells . In support of this , since cation of VSV and does not inhibit replication of Reovirus herpes viruses are known to bind to cells utilizing herparin or EMCV . sulfate proteoglycans, the ability of the Melissa extract to FIG . 7 shows a repeat of Ebola - VSV assay . competitively inhibit herpes virus binding to a heparin - 45 FIG . 8A and FIG . 8B show that neither Hypericum nor agarose resin was tested . As shown in FIG . 2 , the Melissa Lavandula specifically inhibit replication of Ebola - VSV . extract blocked herpes virus binding to the resin as detected by a decrease in the viral glycoprotein B ( GB ) . These and DETAILED DESCRIPTION previous results suggest that Melissa acts by inhibiting herpes virus cellular attachment. 50 The disclosure includes the following : Blocking HSV1 attachment to cells could occur by com 1 . A method of inhibiting viral replication of a filovirus, ponents in Melissa either binding directly to the virus or by the method comprising exposing the filovirus or a binding to the cell . As shown in FIG . 3 , when cells were filovirus - infected cell to an effective amount of an preincubated with the extract, washed and then infected with extract from a plant in the Lamiaceae family , or a HSV1, virus replication was not inhibited . However , if the 55 composition comprising the extract, wherein the expos extract was preincubated with purified HSV1 virions, which ing inhibits viral replication within the cell. were then washed and tested for infectivity, virus replication 2 . A method of treating filovirus infection of a cell, the was inhibited ( FIG . 3 ) . These results support that the active method comprising exposing a filovirus or filovirus constituent( s ) in the Melissa extract bind to the herpes virion infected cell to an effective amount of an extract from and inhibit viral attachment to the cell. The HSV1 glyco - 60 a plant in the Lamiaceae family , or a composition protein B (GB ) is one of the major viral surface proteins comprising the extract , wherein the exposing inhibits involved in binding the virus to heparin sulfate proteogly the entry of the filovirus into the cell. cans on the cell surface . Since Melissa components bind to 3 . A method of preventing filovirus infection of a cell, the the virus and inhibit binding to the cellular heparin sulfate method comprising exposing the cell to an effective proteoglycan , the HSV1 g? is a likely target for Melissa 65 amount of an extract from a plant in the Lamiaceae interaction . In support of this , the Melissa extract was family, or a composition comprising the extract, prior depleted of gB -binding components by affinity chromatog to exposure of the cell to the filovirus, wherein the US 10 , 293 , 012 B2 exposing the cell to the Melissa officinalis extract , or a 19 . The method of the above 17 , wherein the extraction composition comprising Melissa officinalis extract solution comprises glycerin in an amount ranging from inhibits filovirus infection . about 50 % to about 85 % . 4 . A method of inhibiting viral replication of a filovirus, 20 . The method of the above 17 , wherein the extraction the method comprising exposing the filovirus or a 5 solution comprises glycerin in an amount ranging from filovirus - infected cell to an effective amount of Melissa about 65 % to about 80 % . officinalis extract, or a composition comprising Melissa 21 . The method of the above 16 , wherein the extraction officinalis extract , wherein the exposing inhibits viral solution further comprises ethanol. replication within the cell . 22 . The method of the above 21 , wherein the extraction solution comprises ethanol in an amount ranging from 5 . A method of treating filovirus infection of a cell , the about 0 .01 % to about 30 % . method comprising exposing a filovirus or filovirus 23 . The method of the above 21 , wherein the extraction infected cell to an effective amount of Melissa offici solution comprises ethanol in an amount ranging from nalis extract, or a composition comprising Melissa about 10 % to about 25 % . officinalis extract, wherein the exposing inhibits the 1516 24 . The method of the above 21, wherein the extraction entry of the filovirus into the cell . solution comprises ethanol in an amount ranging from 6 . A method of preventing filovirus infection of a cell, the about 15 % to about 20 % . method comprising exposing the cell to an effective 25 . The method of any of the above 14 or 16 - 24 , wherein amount of Melissa officinalis extract, or a composition the Melissa officinalis extract comprises dried plant comprising Melissa officinalis extract , prior to exposure 20 material and extraction solution and the ratio between of the cell to the filovirus , wherein the exposing the cell the dried plant material and the extraction solution is to the Melissa officinalis extract , or a composition from about 1 : 3 to about 1 : 15 . comprising Melissa officinalis extract inhibits filovirus 26 . The method of the above 25, wherein the ratio infection . between the dried plant material and the extraction 7 . The method of any one of the above , wherein the cell 25 solution present in the Melissa officinalis extract is is a human cell. from about 1 : 6 to about 1 : 12 . 8 . A method of treating a subject infected with filovirus, 27 . The method of the above 25 , wherein the ratio the method comprising administering an effective between the dried plant material and the extraction amount of an extract from a plant in the Lamiaceae solution present in the Melissa officinalis extract is family , or a composition comprising the extract , to the 30 from about 1 : 7 to about 1 . 10 . subject , thereby treating the subject infected with filo 28 . The method of any of the above 15 -24 , wherein the virus . Melissa officinalis extract comprises fresh plant mate rial and extraction solution and the ratio between the 9 . A method of preventing infection of a subject with fresh plant material and the extraction solution is from filovirus , the method comprising administering an about 1 : 3 to about 1 : 15 . effective amount of an extract from a plant in the 29. The method of the above 28 , wherein the ratio Lamiaceae family , or a composition comprising the between the fresh plant material and the extraction extract , to the subject prior to exposure of the subject solution present in the Melissa officinalis extract is to filovirus , thereby preventing infection with filovirus . from about 1 : 6 to about 1 : 12 . 10 . A method of treating a subject infected with filovirus, 40 30 . The method of the above 28 , wherein the ratio the method comprising administering an effective between the fresh plant material and the extraction amount of Melissa officinalis extract , or a composition solution present in the Melissa officinalis extract is comprising Melissa officinalis extract, to the subject, from about 1 . 7 to about 1 . 10 . thereby treating the subject infected with filovirus . 31 . The method of any of the above 8 - 30 , further com 11 . A method of preventing infection of a subject with 45 prising administering an additional therapeutic agent. filovirus , the method comprising administering an effective amount of Melissa officinalis extract, or a DEFINITIONS composition comprising Melissa officinalis extract, to the subject prior to exposure of the subject to filovirus, Unless defined otherwise , all technical and scientific thereby preventing infection with filovirus. 50 terms used herein have the same meaning as those com 12 . The method of any of the above , wherein the filovirus monly understood by one of ordinary skill in the art to which is an Ebola virus. this invention belongs . Although methods and materials 13 . The method of any of the above 1 - 11, wherein the similar or equivalent to those described herein can be used filovirus is Marburg virus . in the practice or testing of the present disclosure , suitable 14 . The method of any of the above , wherein the Melissa 55 methods and materials are described below . The materials , officinalis extract comprises dried plant material and methods and examples are illustrative only , and are not extraction solution . intended to be limiting . All publications, patents and other 15 . The method of any of the above 1 - 13 , wherein the documents mentioned herein are incorporated by reference Melissa officinalis extract comprises fresh plant mate in their entirety . rial and extraction solution . 60 Throughout this specification , the word " comprise " or 16 . The method of the above 14 or 15 , wherein the variations such as " comprises” or “ comprising” will be extraction solution comprises water. understood to imply the inclusion of a stated integer or 17 . The method of the above 16 , wherein the extraction groups of integers but not the exclusion of any other integer solution further comprises glycerin . or group of integers . 18 . The method of the above 17 , wherein the extraction 65 The term " a " or " an " may mean more than one of an item . solution comprises glycerin in an amount ranging from The terms “ and ” and “ or” may refer to either the con about 0 .01 % to about 90 % . junctive or disjunctive and mean " and / or” . US 10 , 293 ,012 B2 The term “ about ” means within plus or minus 10 % of a tache, Ajuga, Ajugoides , Alajja , Alvesia , Amasonia , stated value. For example , " about 100 % would refer to any Amethystea , Anisochilus, Anisomeles , Archboldia , Astero number between 90 and 110 . hyptis , Ballota , Basilicum , Becium , Benguellia , Blephilia , The term " effective amount” refers to an amount of an Bostrychanthera , Bovonia , Brachysola , Brazoria , Bystro extract of the disclosure effective to treat a disease or 5 pogon , Calamintha , Callicarpa, Capitanopsis , Capitanya , disorder in a subject. Caryopteris , Catoferia , Cedronella , Ceratanthus , Chaitu The terms " treat” or “ treatment” refer to therapeutic rus, Chamaesphacos, Chaunostoma , Chelonopsis , Chloan treatment and prophylactic measures to obtain a beneficial or thes, Cleonia , Clerodendrum , Clinopodium , Colebrookea , desired result . For purposes of this disclosure , beneficial or Collinsonia , Colquhounia , Comanthosphace, Congea , Con desired results include , but are not limited to , alleviation of 10 radina , Coridothymus, Cornutia , Craniotome, Cryphia , symptoms, diminishment of extent of disease , stabilized Cuminia , Cunila , Cyanostegia , Cyclotrichium , Cymaria , ( i. e ., not worsening ) state of disease , delay or slowing of Dauphinea , Dicerandra , Dicrastylis , Discretitheca , Dorys disease progression , amelioration or palliation of the disease toechas, Dracocephalum , Drepanocaryum , Elsholtzia , state . Those in need of treatment include those already Endostemon , Englerastrum , Eremostachys , Eriope , Erio having the condition or disorder as well as those prone to 15 phyton , Eriopidion , Eriothymus , Erythrochlamys, Euhes have the condition or disorder. perida , Eurysolen , Faradaya , Fuerstia , Galeopsis , Garret The term “ subject” as used herein , includes , but is not tia , Geniosporum , Glechoma, Glechon , Glossocarya , limited to , a human , rat , mouse , guinea pig , monkey, pig , Gmelina , Gomphostemma, Gontscharovia , Hanceola , Hap goat , cow , horse , dog , cat, bird and fowl. In some embodi- lostachys, Haumaniastrum , Hedeoma, Hemiandra , Hemige ments, the subject is a human . 20 nia , Hemiphora , Hemizygia , Hesperozygis , Heterolamium , Methods of Use Hoehnea , Holmskioldia , Holocheila , Holostylon , Hormi The present disclosure provides methods of using an num , Hosea , Hoslundia , Huxleya , Hymenocrater, Hymen extract from a plant in the Lamiaceae family , or a compo opyramis, Hypenia , Hypogomphia , Hyptidendron , Hyptis , sition comprising the extract. The extracts are useful for Hyssopus, Isodictyophorus , Isodon , Isoleucas, Kalaharia , inhibiting viral replication of a filovirus and in treating or 25 Karomia , Keiskea , Killickia , Kudrjaschevia , Kurzamra , preventing an infection by a filovirus. Lachnostachys, Lagochilus, Lagopsis , Lallemantia , Lamio In one particular embodiment, the present disclosure phlomis , Lamium , Lavandula , Leocus, Leonotis, Leonurus, provides a method of inhibiting viral replication of a filo - Lepechinia , Leucas, Leucophae , Leucosceptrum , Limni virus. The method comprises exposing the filovirus or a boza , Lophanthus, Loxocalyx , Lycopus, Macbridea , Madla filovirus- infected cell to an effective amount of an extract 30 bium , Mallophora , Marmoritis ,Marrubium , Marsypianthes, from a plant in the Lamiaceae family, or a composition Matsumurella , Meehania , Melissa , Melittis, Mentha , Meri comprising the extract . The step of exposing the filovirus or andra , Mesona, Metastachydium , Microcorys, Micromeria , filovirus - infected cell to the extract inhibits viral replication Microtoena , Minthostachys , Moluccella , Monarda , Monar within the cell. della , Monochilus, Mosla , Neoeplingia , Neohyptis , Neora In another particular embodiment, the present disclosure 35 pinia , Nepeta , New castelia , Nosema , Notochaete, Obte provides a method of treating filovirus infection of a cell. gomeria , Ocimum , Octomeron , Ombrocharis , Oncinocalyx , The method comprises exposing a filovirus or filovirus - Origanum , Orthosiphon , Otostegia , Ovieda, Oxera , Panze infected cell to an effective amount of an extract from a plant rina , Paralamium , Paraphlomis , Paravitex, Peltodon , Pen in the Lamiaceae family , or a composition comprising the tapleura , Perilla , Perillula , Peronema, Perovskia , Perri extract. The step of exposing the filovirus or filovirus - 40 erastrum , Petitia , Petraeovitex , Phlomidoschema, Phlomis , infected cell to the extract inhibits the entry of the filovirus Phlomoides, Phyllostegia , Physopsis , Physostegia , Piloble into the cell. phis , Pitardia , Pityrodia , Platostoma, Plectranthus, In another particular embodiment, the present disclosure Pogogyne , Pogostemon , Poliomintha, Prasium , Premna , provides a method of preventing filovirus infection of a cell . Prostanthera , Prunella , Pseuderemostachys, Pseudocar The method comprises exposing the cell to an effective 45 pidium , Pseudocaryopteris , Pseudomarrubium , Puntia , amount of an extract from a plant in the Lamiaceae family, Pycnanthemum , Pycnostachys, Rabdosiella , Renschia , or a composition comprising the extract , prior to exposure of Rhabdocaulon , Rhaphiodon , Rhododon , Rosmarinus, Ros the cell to the filovirus . The step of exposing the cell to the trinucula , Rotheca, Roylea , Rubiteucris , Rydingia , Sabau Melissa officinalis extract , or a composition comprising dia , Saccocalyx , Salazaria , Salvia , Satureja , Schizonepeta , Melissa officinalis extract inhibits filovirus infection . 50 Schnabelia , Scutellaria , Sideritis , Siphocranion , Solenoste In another particular embodiment, the present disclosure mon , Spartothamnella , Sphenodesme, Stachydeoma , provides a method of treating a subject infected with filo - Stachyopsis , Stachys, Stenogyne, Sulaimania , Suzukia , Sym virus . The method comprises administering an effective phorema, Symphostemon , Synandra , Syncolostemon , Tec amount of an extract from a plant in the Lamiaceae family , tona , Teijsmanniodendron , Tetraclea , Tetradenia , Teu or a composition comprising the extract , to the subject, 55 cridium , Teucrium , Thorncroftia , Thuspeinanta , Thymbra , thereby treating the subject infected with filovirus . Thymus, Tinnea , Trichostema, Tripora , Tsoongia , Vitex, Vit In another particular embodiment, the present disclosure icipremna , Volkameria , Warnockia, Wenchengia , Westrin provides a method of preventing infection of a subject with gia , Wiedemannia , Wrixonia, Xenopoma, Zataria , Zhumeria filovirus . The method comprises administering an effective and Ziziphora . amount of an extract from a plant in the Lamiaceae family , 60 In various embodiments , the extract is from Melissa or a composition comprising the extract, to the subject prior officinalis . to exposure of the subject to filovirus , thereby preventing The methods disclosed herein can be used against any infection with filovirus . filovirus. In one embodiment, the filovirus is an Ebola virus. Examples of plants from the Lamiaceae family that can be In another embodiment, the filovirus is a Marburg virus . used in the methods of the present disclosure include 65 In various embodiments in which the methods are used to Acanthomintha , Achyrospermum , Acinos, Acrocephalus, treat or prevent viral infection of a cell, the cell can be a Acrotome, Acrymia , Adelosa , Aegiphila , Aeollanthus, Agas - human cell.

US 10 ,293 ,012 B2 11 . The method of claim 1 , wherein the filovirus is an Ebola virus . 12 . The method of claim 1 , wherein the filovirus is Marburg virus. 13. The method of claim 1 , wherein the extract comprises 5 dried plant material and extraction solution . 14 . The method of claim 1 , wherein the extract comprises fresh plant material and extraction solution . 15 . The method of claim 13 , wherein the extraction solution comprises water. 10 16 . The method of claim 15 , wherein the extraction solution further comprises glycerin . 17 . The method of claim 16 , wherein the extraction solution comprises glycerin in an amount ranging from about 0 .01 % to about 90 % . 15 18 . The method of claim 15 , wherein the extraction solution further comprises ethanol . 19 . The method of claim 18 , wherein the extraction solution comprises ethanol in an amount ranging from about 0 .01 % to about 30 % . 20