Corona 2020 DietrichKlinghardtMD,PhD

March2020AthankyoutoindependentresearcherDorisLoh,

forhertremendouscontribution

Disclaimer:AlladvicegivenoutbyDr.KlinghardtandtheKlinghardtInstituteisforgeneralguidanceandinformationalpurposesonly.Readersareencouragedtoconfirmtheinformationprovidedwithothersources.Patientsandconsumersshouldreviewtheinformationcarefullywiththeirprofessionalhealthcareprovider.Theinformationisnotintendedtoreplacemedicaladviceofferedbyotherphysicians.Dr.KlinghardtandTheKlinghardtInstitutewillnotbeliableforanydirect,indirect,consequential,special,exemplary,orotherdamagesarisingtherefrom.

What are we allowed to know? Coronavirusescompriseavastfamilyofviruses,7ofwhichareknowntocausediseaseinhumans.Somecoronavirusesthattypicallyinfectanimalshaveevolvedtoinfecthumans.SARS-CoV-2islikelyonesuchvirus,postulatedtohaveoriginatedinalargeanimalandseafoodmarket.Recentcasesinvolveindividualswhoreportednocontactwithanimalmarkets,suggestingthatthevirusisnowspreadingfrompersontoperson.Severeacuterespiratorysyndrome(SARS)andMiddleEastrespiratorysyndrome(MERS)arealsocausedbycoronavirusesthat“jumped”fromanimalstohumans.Morethan8,000individualsdevelopedSARS,nearly800ofwhomdiedoftheillness(mortalityrateofapproximately10%),beforeitwascontrolledin2003.MERScontinuestoresurfaceinsporadiccases.Atotalof2,465laboratory-confirmedcasesofMERShavebeenreportedsince2012,resultingin850deaths(mortalityrateof34.5%).ThefullgenomeofSARS-CoV-2wasfirstpostedbyChinesehealthauthoritiessoonaftertheinitialdetection,facilitatingviralcharacterizationanddiagnosis.TheCDCanalyzedthegenomefromthefirstUSpatientwhodevelopedtheinfectiononJanuary24,2020,concludingthatthesequenceisnearlyidenticaltothesequencesreportedbyChina(CDC.CoronavirusDisease2019(COVID-19):COVID-19SituationSummary.CDC.Availableathttps://www.cdc.gov/coronavirus/2019-ncov/summary.html.February29,2020).SARS-CoV-2isagroup2bbeta-coronavirusthathasatleast70%similarityingeneticsequencetoSARS-CoV.LikeMERS-CoVandSARS-CoV,SARS-CoV-2isbelievedtohaveoriginatedinbats.PrognosisandSeverityofCOVID-19ComparedWithSARSandMERS:.Earlyintheoutbreak,WHOreportedthatseverecasesinChinahadmostlybeenreportedinadultsolderthan40yearsoldwithsignificantcomorbiditiesandskewedtowardmen,althoughthispatternmaybechanging.(OttoMA.WuhanVirus:WhatCliniciansNeedtoKnow.MedscapeMedicalNews.Availableathttps://www.medscape.com/viewarticle/924268.January27,2020).EarlyreportshavedescribedCOVID-19asclinicallymilderthanMERSorSARSintermsofseverityandcasefatalityrate.Thusfar,thefatalityrateforCOVID-19appearstobearound2%(0.5-20%dependentonagegroup).

Covid-19: the recent history •  Illnesscausedby“SARS-CoV-2”(severeacuterespiratorysyndromecoronavirus2)wasrecentlytermed“COVID-19”bytheWHO,thenewacronymderivedfrom"coronavirusdisease2019."

•  2019-2020Outbreak:AsofMarch6,2020,COVID-19hasbeenconfirmedinmorethan100,000individuals(mostlyinChina)andhasresultedinmorethan3,400deaths.OutsideofChina,infectionshavebeenreportedinanincreasingnumberofcountries

•  Inaninitialreportof41patientsinfectedinWuhan,China,Huangetalreporteda78%malepredominance,with32%ofallpatientsreportingunderlyingdisease.Themostcommonclinicfindingwasfever(98%),followedbycough(76%)andmyalgia/fatigue(44%).Headache,sputumproduction,anddiarrheawerelesscommon.Theclinicalcoursewascharacterizedbythedevelopmentofdyspneain55%ofpatientsandlymphopeniain66%.Allpatientswithpneumoniahadabnormallungimagingfindings.Acuterespiratorydistresssyndrome(ARDS)developedin29%ofpatients,andground-glassopacitiesarecommononCTscans.

Transmission Transmissionisbelievedtooccurviarespiratorydropletsfromcoughingandsneezing,aswithotherrespiratorypathogens.AccordingtotheWHO,thespreadofSARS-CoV-2inChinaseemstobelargelylimitedtofamilymembers,healthcareproviders,andotherclosecontactsandisprobablybeingtransmittedbyrespiratorydroplets.January27,2020;Accessed:January27,2020.)Relativelyfewyoungchildrenhavebeenidentifiedandthoseinfectedseemtohavemildillness(WeiM,YuanJ,LiuY,FuT,YuX,ZhangZJ.NovelCoronavirusInfectioninHospitalizedInfantsUnder1YearofAgeinChina.JAMA.2020Feb14)Recentlyreleaseddatahavesuggestedthatasymptomaticpatientsarestillabletotransmitinfection.Thisraisesconcernsfortheeffectivenessofisolation.Zouetalfollowedviralexpressionthroughinfectionvianasalandthroatswabsinasmallcohortofpatients.Theyfoundincreasesinviralloadsatthetimethatthepatientsbecamesymptomatic.Onepatientneverdevelopedsymptomsbutwassheddingvirusbeginningatday7afterpresumedinfection(ZouL,RuanF,HuangM,LiangL,HuangH,HongZ,etal.SARS-CoV-2ViralLoadinUpperRespiratorySpecimensofInfectedPatients.NEnglJMed.2020Feb19)Theincubationtimefornewinfectionswasfoundtobe5.2days,witharangeof4.1-7days.Thelongesttimefrominfectiontosymptomsseemedtobe12.5days.Atthispoint,theepidemichadbeendoublingapproximatelyevery7days,andthebasereproductivenumberwas2.2(meaningeverypatientinfectsanaverageof2.2others)(LiQ,GuanX,WuP,WangX,etal.EarlyTransmissionDynamicsinWuhan,China,ofNovelCoronavirus-InfectedPneumonia.NEnglJMed.2020Jan29.)US:OfthedeathsinthecityofKirkland,Washington,6occurredinthesamehospital(Evergreenhospital).KirklandpridesitselfasbeingoneofthefirsttownsintheUSwiredfor5G.EvergreenhospitalhasaccordingtoourownmeasurementsthehighestlevelsofWiFiexposureevermeasuredinahospital.

Diagnosis GovernmentLaboratorytesting:Iflaboratorytestingconfirmsanalternatepathogen,SARS-CoV-2canbeexcluded,althoughthisrecommendationmaychangeinthefuture(CDCHealthAlertNetwork.UpdateandInterimGuidanceonOutbreakof2019NovelCoronavirus(2019-nCoV)inWuhan,China.CDC.Availableathttps://emergency.cdc.gov/han/han00426.asp.January17,2020;Accessed:January27,2020)TheCDChasdevelopedadiagnostictestfordetectionofthevirusandhasreceivedspecialemergencyauthorizationfromtheFDAforitsuse.Thetestisareal-timereversetranscription–polymerasechainreaction(rRT-PCR)assaythatcanbeusedtodiagnosethevirusinrespiratoryandserumsamplesfromclinicalspecimens.(CDC.CoronavirusDisease2019(COVID-19):COVID-19SituationSummary.CDC.Availableathttps://www.cdc.gov/coronavirus/2019-ncov/summary.html.February29,2020;Accessed:March2,2020)

Practicaltipsforthehealthpractitioner:Symptoms:mildtomoderatefever,drycough,muscleachesandfatigueLaboratory:Lowwbcandlymphocytecountinthecbc:Leukopeniaandlymphopeniawerecommonamongearlycases(HuiDS,IAzharE,MadaniTA,NtoumiF,KockR,DarO,etal.Thecontinuing2019-nCoVepidemicthreatofnovelcoronavirusestoglobalhealth-Thelatest2019novelcoronavirusoutbreakinWuhan,China.IntJInfectDis.2020Jan14.91:264-266.HuangC,WangY,LiX,RenL,ZhaoJ,HuY,etal.Clinicalfeaturesofpatientsinfectedwith2019novelcoronavirusinWuhan,China.Lancet.2020Jan24.)Chestradiography:Chestradiographymayrevealpulmonaryinfiltrates(BogochII,WattsA,Thomas-BachliA,HuberC,KraemerMUG,KhanK.PneumoniaofUnknownEtiologyinWuhan,China:PotentialforInternationalSpreadViaCommercialAirTravel.JTravelMed.2020Jan14)CTscanning:CTscanmayrevealground-glassinfiltratesorconsolidation,almostalwaysbilateral(HuangC,WangY,LiX,RenL,ZhaoJ,HuY,etal.Clinicalfeaturesofpatientsinfectedwith2019novelcoronavirusinWuhan,China.Lancet.2020Jan24.

NovaccineiscurrentlyavailableforSARS-CoV-2.Avoidanceistheprincipalmethodofdeterrence.NospecificantiviraltreatmentisrecommendedforCOVID-19.Infectedpatientsshouldreceivesupportivecaretohelpalleviatesymptoms.Vitalorganfunctionshouldbesupportedinseverecases.(CDC.2019NovelCoronavirus,Wuhan,China:Prevention&Treatment.CDC.Availableathttps://www.cdc.gov/coronavirus/2019-ncov/about/prevention-treatment.html.January26,2020)AccordingtoaconsensusstatementfromamulticentercollaborationgroupinChina,chloroquinephosphate500-mgtwicedailyintabletformfor10daysmaybeconsideredinpatientswithCOVID-19pneumonia(MulticentercollaborationgroupofDepartmentofScienceandTechnologyofGuangdongProvinceandHealthCommissionofGuangdongProvinceforchloroquineinthetreatmentofnovelcoronaviruspneumonia.[Expertconsensusonchloroquinephosphateforthetreatmentofnovelcoronaviruspneumonia].ZhonghuaJieHeHeHuXiZaZhi.2020Feb20.43:E019.).

WangetalreportedthatchloroquineeffectivelyinhibitsSARS-CoV-2invitro.(WangM,CaoR,ZhangL,YangX,LiuJ,XuM,etal.Remdesivirandchloroquineeffectivelyinhibittherecentlyemergednovelcoronavirus(2019-nCoV)invitro.CellRes.2020Feb4)Thesamearticlealsohighlightsthein-vitroeffectivenessorNitazoxanide(Alinia,Daxon)nexttochloroquine.Aliniaisverywelltoleratedandfamiliartoourpatients.ItwasalsofoundveryeffectiveintreatingthemoredeadlyMERS-coronavirus(“Nitazoxanide,anewdrugcandidateforthetreatmentofMiddleEastrespiratorysyndromecoronavirus”;JournalofInfectionandPublicHealth.Volume9,Issue3,May–June2016,Pages227-230;Jean-FrançoisRossignol

TreatmentandPreventionofCOVID-19(as reported in Medscape)

An Effective Treatment for Coronavirus (COVID-19) - published today! Presented by: James M. Todaro, MD (Columbia MD, jtodaro2@gmail.com) and Gregory J. Rigano, Esq. (grigano1@jhu.edu) In consultation with Stanford University School of Medicine, UAB School of Medicine and National Academy of Sciences researchers; March 13, 2020 SPANISH:https://docs.google.com/document/d/e/2PACX-1vR1adodKPhWalV9djnerI2x_v1LGgGyhZZxpl0O5r-ZNyDdagqFq1rTCxXBqaeicfxgvypDOqKCZVyV/pubTranslationby:CeliaMartínez-Aceves(YaleB.S.Candidate2021;celia.martinez-aceves@yale.edu),MartínMartínez(MITB.S.2017;martin.martinez.mit@gmail.com)

ITALIAN:https://docs.google.com/document/d/e/2PACX-1vSjPNh_WX6FXUIE3OaA3ScsW7yIH3-SpZyYzElNQUNuJvDmD9eFzM29mVXeaYRY-rjGv52wkrZNa7tb/pubTranslationby:GoogleTranslateandeditedbyRossShulman,CornellUniversityMS'20ross.shulman@gmail.com

Summary

RecentguidelinesfromSouthKoreaandChinareportthatchloroquineisaneffectiveantiviraltherapeutictreatmentagainstCoronavirusDisease2019.Useofchloroquine(tablets)isshowingfavorableoutcomesinhumansinfectedwithCoronavirusincludingfastertimetorecoveryandshorterhospitalstay.USCDCresearchshowsthatchloroquinealsohasstrongpotentialasaprophylactic(preventative)measureagainstcoronavirusinthelab,whilewewaitforavaccinetobedeveloped.Chloroquineisaninexpensive,globallyavailabledrugthathasbeeninwidespreadhumanusesince1945againstmalaria,autoimmuneandvariousotherconditions.

AschloroquineisnotavailableinKorea,doctorscouldconsiderhydroxychloroquine400mgorallyperday(Hydroxychloroquineisananalogofchloroquineusedagainstmalaria,autoimmunedisorders,etc.Itiswidelyavailableaswell).

Thetreatmentissuitablefor7-10days,whichcanbeshortenedorextendeddependingonclinicalprogress.TheUKhasbannedtheexportofChloroquine[13]

AsofFebruary26,2020,theUKgovernmenthasaddedchloroquinetothelistofmedicinesthatcannotbeparallelexportedfromtheUK.Chloroquinewasneveronthislistbefore.Thislikelyhappenedbecauseofthegrowingbodyofevidenceofchloroquine’seffectivenessagainstcoronavirus.

BackgroundArecentwellcontrolledclinicalstudyconductedbyDidierRaoult�M.D/Ph.D,et.alinFrancehasshownthat100%ofpatientsthatreceivedacombinationofHCQandAzithromycintestednegativeandwerevirologicallycuredwithin6daysoftreatment.

Please cite this work as Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949

Results(40pateints-20patientsintreatmentgroup,20cures)•  Sixpatientswereasymptomatic,22hadupperrespiratorytractinfectionsymptomsandeighthadlowerrespiratorytractinfectionsymptoms.

•  TwentycasesweretreatedinthisstudyandshowedasignificantreductionoftheviralcarriageatDay6-postinclusioncomparedtocontrols,

•  andmuchloweraveragecarryingdurationthanreportedofuntreatedpatientsintheliterature.

• Azithromycinaddedtohydroxychloroquinewassignificantlymoreefficientforviruselimination

Generalmeasuresforpreventionofviralrespiratoryinfections include the following: •  Handwashingwithsoapandwaterforatleast20seconds.A60%alcohol-basedhandsanitizer

maybeusedifsoapandwaterareunavailable.•  Individualsshouldavoidtouchingtheireyes,nose,andmouthwithunwashedhands.•  Individualsshouldavoidclosecontactwithsickpeople.•  Sickpeopleshouldresponsiblyselfisolate/stayathome(e.g.,fromwork,school).•  Coughsandsneezesshouldbecoveredwithatissue,followedbydisposalofthetissueinthetrash.

•  Frequentlytouchedobjectsandsurfacesshouldbecleanedanddisinfectedregularly.•  FollowingthemodeloftheHongKongprotocolcitizensareadvisedtowearfacialmasksatalltimeswheninthepresenceofotherpeoplebothasameansofprotectionandspreadofthevirus

Infectioncontrol:ThosewhoareunderinvestigationforCOVID-19shouldbeevaluatedinaprivateroomwiththedoorclosed(anairborneinfectionisolationroomisideal)andaskedtowearasurgicalmask.Allotherstandardcontactandairborneprecautionsshouldbeobserved,andtreatinghealthcarepersonnelshouldweareyeprotection(CDC.2019NovelCoronavirus,Wuhan,China:InterimHealthcareInfectionPreventionandControlRecommendationsforPatientsUnderInvestigationfor2019NovelCoronavirus.CDC.Availableathttps://www.cdc.gov/coronavirus/2019-ncov/infection-control.html.January18,2020)

CoronaMarch2020:whatallofusshouldalsoknow! Covid-19cansurvive72hrs(someestimateupto7days)onsurfacesoutsidethebody.Disinfectingiscrucial!Onceinsidethebody,Covid-19livesmostlyonthesurfaceoftissues.Earlyviralattachment:thereisactiveviralreplicationofSARS-CoV-2inthethroatduringthefirst5daysaftersymptomsonset.Clinicalpresentationandvirologicalassessmentofhospitalizedcasesofcoronavirusdisease2019inatravel-associatedtransmissionclusterhttps://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1.full.pdf

ANK:withthefirstsignsofillness(fever,sorethroat,unwellness)spraypropolis(KiSciencePropolisPlus)-alternatingwithHOCLspray-frequentlyontothesorethroatarea.AlsosprayHOCLintheeyesandnose(hourlyormoreoften)Propolisstimulatesanti-viralimmunityinmucousmembranes(Ferreira,L.dasN.,etal."Effectoftheethanolicextractfromgreenpropolisonproductionofantibodiesafterimmunizationagainstcanineparvovirus(CPV)andcaninecoronavirus(CCoV)."BrazilianJournalofVeterinaryResearchandAnimalScience49.2(2012):116-121)Advancedillness:Thehighestviralloadwasfoundinspecimensfrombronchoalveolarlavagefluid(93%),followedbysputum(72%),nasal(63%)fibrobronchoscopebrushbiopsy(46%),pharyngealswabs(32%),feces(29%),andblood(1%).Interestingly,noneofthe72urinespecimenstestedpositiveforthecoronavirus(DetectionofSARS-CoV-2inDifferentTypesofClinicalSpecimens|GlobalHealth|JAMA|JAMANetworkhttps://jamanetwork.com/journals/jama/fullarticle/2762997)

ANK:continuethePropolisandHOCLsprayasmuchascircumstancesallowplusaddtheANKtreatmentsuggestions(seefollowingpages)

StabilizedHOCL:themistthatrocksSong,JoonYoung,etal."ViralsheddingandenvironmentalcleaninginMiddleEastrespiratorysyndromecoronavirusinfection."Infection&chemotherapy47.4(2015):252-255. Abstract:Viralsheddinglasted31and19daysfromsymptomonsetintwopatientswitheastrespiratorysyndromecoronavirus(MERS-CoV)pneumonia,respectively.Environmentalreal-timeRT-PCRwasweaklypositiveforbedguardrailandmonitors.Evenaftercleaningthemonitorswith70%alcohol-baseddisinfectant,RT-PCRwasstillweaklypositive,andconvertedtonegativeonlyafterwipingwithdilutedsodiumchlorite.FurtherstudiesarerequiredtoclarifytheappropriatemethodstocleanenvironmentsduringandaftertreatmentofpatientswithMERS-CoVinfection.Ono,Tomoko,etal."Microbicidaleffectofweakacidhypochloroussolutiononvariousmicroorganisms."Biocontrolscience17.3(2012):129-133.Abstract:WeinvestigatedthemicrobicidaleffectofweakacidhypochloroussolutionsofpH5.0-6.0,producedbymixingNaClOandHClinwater,againstvariousbacteria,fungi,andvirusinvitro.Theweakacidhypochloroussolutionhadexcellentmicrobicidaleffectagainstabroadmicrobicidalspectrumofstandardstrainsandclinicalisolatesinashorttime.ThemicrobicidaleffectsofhypochloroussolutionsdidnotdependontheavailablechlorineconcentrationbutontheHOClconcentration.Theseresultsshowthattheweakacidhypochloroussolutionhaspracticalapplicabilityinsuchplacesashospitalsandestablishmentsrelatedtothefoodindustry.Lewis,M.R."NovelCoronavirus(2019-nCoV)ScopeforAqualutionHypochlorousAcidSolutionforEffectivePreventionandControlHypochlorousacidisnotspecificallytestedagainst2019nCoV–nodisinfectantis-butitistestedandefficaciousagainstawiderangeofmicroorganismsincludingspores,bacteriaandotherviruses(envelopedandnon-enveloped)leadingtothereasonableconclusionthatitwillbeeffective.hypochlorousacidisfastactingwithcontacttimestypicallylessthanaminute.Itissafeforpeopleandsafefortheenvironment

"Stabilizedhypochlorousaciddisinfectionforhighlyvulnerablepopulations:BrioHOCL™wounddisinfectionandareadecontamination" 2017 IEEE Global Humanitarian Technology Conference (GHTC). IEEE, 2017. Rasmussen, Eric D., and Jeffrey F. Williams. A recent certificate from UW: ENVIRONMENTAL&OCCUPATIONALHEALTHSCIENCES______________________________________________SCHOOLofPUBLICHEALTH.UNIVERSITYofWASHINGTON3/4/2016Towhomitmayconcern:AspartofourongoingcollaborationwithBriotechInc,inWashington,mymicrobiologylaboratoryhasbeenevaluatingtheefficacyofBrioHOClagainsthumancoronavirusOC43.Studiesconductedtodateindicateatleasta99.999%reductionintheinfectivityofhumancoronavirusupon10minexposuretoBrioHOClsolution.Furtherworkisunderwaytocharacterizethisimportantfinding.JohnScottMeschkeProfessorandDirectorofEnvironmentalandOccupationalHealthMicrobiologyLabDepartmentofEnvironmentalandOccupationalHealthSciencesSchoolofPublicHealth,UniversityofWashington

Currentpromisingapproachestotreatment(March 17, 2020) Treatmentofapossiblyinfectedordiagnosedpatient1.VitaminC:Ascorbicacidcandose-dependentlyinhibitNLRP3Inflammasomesbothinvitroandinvivo,decreasingIL-1βsecretion,withoutinducinganycytotoxiceffectsnorcelldeath(VitaminCinhibitstheactivationoftheNLRP3inflammasomebyscavengingmitochondrialROShttps://www.researchgate.net/publication/305624280)

InapressreleasefromaChinesehospitalspecializingininfectiousdiseaseitwasobservedthatintravenousvitaminCwasextremelyeffectiveintreatingaffectedandinfectedpatients:thedoseof100-200mg/kgbodyweightwasgivenintravenouslyfor3daysinarow(thisequalstoonly7.5–15gramsfora75kg(180lbs.)person(⼤大剂量量维⽣生素C治疗新冠肺炎的交⼆二⽅方案发布时间：2020-02-2111:00:56浏览次数：5870).Thetreatmentisscheduledforagovernmentsponsoredtrial:“ClinicalTrials.govdentifierNCT04264533,ZhiYongPeng,ZhongnanHospital”

IntheUS,thepioneersoforthomolecularmedicinealsopublishedaconsensuspaperontheuseofVitC:OrthomolecularMedicineNewsService,Feb16,2020“EarlyLargeDoseIntravenousVitaminCistheTreatmentofChoicefor2019-nCovinfectedPneumonia”RichardZCheng,MD,PhD;HanpingShi,MD,PhD;AtsuoYanagisawa,MD,PhD;ThomasLevy,MD,JD;AndrewSaul,PhD.

ANKPrevention:BasedontheadvicefromtheChinesehospitalstaffwerecommendthefollowingtoallofourpatients:takeaminimumof2000mgVitCperday.Useamixofliposomal/non-liposomalvitC,byadding1-2tspofMicroPhostothepreparedVitCdrinkandstirringitvigorously.Dividethedoseinhalfanddrinktwicedaily.2.Alinia:BasedontheMERS-CoVexperienceyearsago(andtheWangarticle/invitrostudyofCovid-19inCellRes2020)gained,use1000mgNitazoxanidetwicedailyfor10days.Nitazoxanideisusuallywelltolerated.3.Chloroquinephosphate(Plaquenil):500mgtwicedailyfor10days(mostLymeliterateMDsarefamiliarwiththeuseofchloroquineandpossiblesideeffects)4.Notpublished,butverysimilarchemical/biologicalproperties:Artesunate(250mg/day.v.)for10consecutivedays(severeillness).Inmildercases,artemisiaannuatincturemayworkwell(KiScience:SweetAnnieandArtemisiaFortepowder)

Furins: Andrographis and Vit.C against SARS-Co2 Furin:thefuringeneencodesforthefurinprotein.Themembersofthis“family”processlatentprecursorproteinsintotheirbiologicallyactiveproducts.FurinisenrichedintheGolgiapparatus,whereitfunctionstocleaveotherproteinsintotheirmature/activeforms.theenvelopeproteinsofvirusesofSARS-CoV2mustbecleavedbyfurinorfurin-likeproteasestobecomefullyfunctional.(CoutardB,ValleC,deLamballerieX,CanardB,SeidahNG,DecrolyE(February2020)."Thespikeglycoproteinofthenewcoronavirus2019-nCoVcontainsafurin-likecleavagesiteabsentinCoVofthesameclade".AntiviralResearch.176:104742.doi:10.1016/j.antiviral.2020.104742.PMID32057769.)

Thefurincleavageallowsefficientvirusentryintobasicallyallcelltypes,makingtheCOVID-19easilytransmissibleatratesupto1,000timesgreaterthanthevirulentSARScoronavirusThepresenceoffurinenzymesonallcellsurfacescleavesandactivatestheSARS-CoV-2inawiderangeoftissuesandorgans.ActivatedSARS-CoV-2thenunleashesNLRP3inflammasomes,initiatingaflurryofimmunereactionsthatcanresultindeadlycytokinestorms.(FurincleavagesiteintheSARS-CoV-2coronavirusglycoproteinhttp://www.virology.ws/2020/02/13/furin-cleavage-site-in-the-sars-cov-2-coronavirus-glycoprotein)

Andrographispaniculataisapowerfulanti-furinstrategyandshouldbeutilizedearlyinthetreatmentofinfectedorsuspectedindividuals!Basak,Ajoy,etal."Inhibitionofproproteinconvertases-1,-7andfurinbyditerpinesofAndrographispaniculataandtheirsuccinoylesters."BiochemicalJournal338.1(1999):107-113.

Basak,Ajoy."Inhibitorsofproproteinconvertases."Journalofmolecularmedicine83.11(2005):844-855.VitaminChasalsobeenshowntohaveanti-furinproperties(COVID-19,Furins&Hypoxia–TheVitaminCConnection–EvolutaMente.ithttps://www.evolutamente.it/covid-19-furins-cancer-a-tale-of-vitamin-c-hif/)ANK:weuseeither1.   AndrographisinaKiSciencesynergisticmixwithotherherbs:“Astrasmile”(prevention:1dropperful4-6times/day;

treatment:1dropperfulhourly)2.   Plantbasedherbalmix:“Andrographis+”(prevention:1dropperful4times/day;treatment:1dropperfulhourly)3.   HighdoseVitaminC-CompleteAscorbateSupportKiScience

TheInflammasome,VitaminC,Melatonin-andHummingWhatmakesCovid-19potentiallylethalistheactivationoftheinflammasometriggeringthedreaded“cytokinestorm”

Inflammasomesaremultiproteinoligomersinthecytosolofthecellsoftheinnateimmunesystemresponsiblefortheactivationofinflammatoryresponses.Covid-19activationoftheinflammasomepromotesthesecretionofpro-inflammatorycytokinesinterleukin1β(IL-1β)andinterleukin18(IL-18).Recently,theNLRP-3inflammasomehasbeenidentifiedaskeytotheinductionofADRS/ALI(“AcuteRespiratoryDistressSyndrome”and“AcuteLungInjury”)

(CriticalrolefortheNLRP-3inflammasomeduringacutelunginjuryhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061751)

VitC,melatoninandsimplehumminghavebeenshowntosilencetheNLRP3inflammasome(discussionlater).IncountrieswhereMelatoninisnotavailable,propoliscanbesubstituted.

Viroporins and the NLRP3 inflammasomes Viroporinsareionchannelproteinsencodedbyviruses.Viroporinsarecapableofassemblingintoionchannelsorporesinthehost’scellmembrane,renderingitmorepermeableandthusfacilitatingtheexitofvirionsfromthecell.SARS-CoVexpressesviroporins(Nieto-TorresJL,Verdiá-BáguenaC,Castaño-RodriguezC,AguilellaVM,EnjuanesL(July2015)."RelevanceofViroporinIonChannelActivityonViralReplicationandPathogenesis".Viruses.7(7):3552–73.doi:10.3390/v7072786.PMC4517115.PMID26151305.

Viroporinsplaycriticalrolesinvirusreplicationandpathogenesis–especiallyintheCovid-19relatedcytokinestormthatisresponsibleforthescarylungproblems.SARS-CoVviroporinproteinsformprotein-lipidchannelsincellmembranesthatalsoallowpassageofcalciumions.TheseionchannelmovementsinvolvingcalciumarespecifictriggersintheactivationofNLRP-3inflammasomes,resultingintheoverproductionofpro-inflammatoryIL-1βcytokines.CalciumtransportthroughtheseEproteinionchannelsinitiatesthecascadeofcytokineproductionthatmayeventuallyresultinuncontrollablecytokinestorms,andARDS/ALIinbilateralinterstitialpneumonia.ORF3aviroporinisHIGHLYexpressedininfectedcells.ANK:WiFi/radiowavesalsofacilitatetheentryofcalciumintothecell,triggeringthecytokinestorm.ShieldingandWiFihygieneareanessentialtreatmentofCovid-19

MelatoninMelatoninhasrecentlybeenshowntoreduceIL-1βsecretionandattenuateinflammasome-associatedvasculardisordersbyimprovingendothelialleakageandsuppressingNLRP3inflammasomes(Melatonininhibitsinflammasome-associatedactivationofendotheliumandmacrophagesattenuatingpulmonaryarterialhypertension|CardiovascularResearch|OxfordAcademichttps://academic.oup.com/cardiovascres/advance-article-abstract/doi/10.1093/cvr/cvz312/5644338?redirectedFrom=fulltext)Thisalsomeansthatifapatient,regardlessofage,hasadequatemelatonin,theinfectiousnessofCOVID-19willbegreatlyreduced,andthechancesofdevelopingARDS/ALIsignificantlydiminished.Melatoninisthereasonwhychildrenundertheageof9seldomexhibitseveresymptoms.Infact,childrenmayexhibitmildorevennosymptomsatall,eventhoughtheyhavebeeninfectedbySARS-CoV-2(FrequentlyAskedQuestionsandAnswers:CoronavirusDisease-2019(COVID-19)andChildrenhttps://www.cdc.gov/coronavirus/2019-ncov/specific-groups/children-faq.html)

MelatoninwasshowntoinhibitNLRP-3inflammasomesinmicewithmyocardialsepticconditions,transformingseveremyocardialinflammationintomildersymptoms,preventingcardiacfailure,andsignificantlyenhancedsurvivalratesofsepticmice(Melatoninadministrationtowild-typemiceandnontreatedNLRP3mutantmicesharesimilarinhibitionoftheinflammatoryresponseduringsepsis–Rahim–2017–JournalofPinealResearch–WileyOnlineLibraryhttps://onlinelibrary.wiley.com/doi/abs/10.1111/jpi.12410Melatoninattenuatessepsis-inducedcardiacdysfunctionviaaPI3K/Akt-dependentmechanism|SpringerLinkhttps://link.springer.com/article/10.1007%2Fs00395-015-0526-1)

MelatoninVoltetal.showedthatacuteadministrationofmelatonincouldcounteractsevereinflammatoryresponses(SameMoleculebutDifferentExpression:AgingandSepsisTriggerNLRP-3InflammasomeActivation,aTargetofMelatonin–PubMedhttps://pubmed.ncbi.nlm.nih.gov/26681113-same-molecule-but-different-expression-aging-and-sepsis-trigger-nlrp3-inflammasome-activation-a-target-of-melatonin/)Inrodentmodelsofacuterespiratorydistresssyndrome(ARDS),combinedtreatmentofmelatoninandmitochondriasignificantlyattenuatedprogressionofARDS(Systemiccombinedmelatonin–mitochondriatreatmentimprovesacuterespiratorydistresssyndromeintherat–Sun–2015–JournalofPinealResearch–WileyOnlineLibraryhttps://onlinelibrary.wiley.com/doi/10.1111/jpi.12199)Thecriticalfunctionofsuppressingcytokinestormstopreventprogressionofacuterespiratorydistresssyndrome(ARDS)andrespiratoryfailureininfectedpatientswasclearlydemonstratedinastudybyHuangetal.(2019).Co-treatmentoftheseinfectedrodentswithmelatoninandanantiviraldrugsignificantlyincreasedtheirsurvivalratescomparedtomicetreatedonlywithantiviralsalone(Melatoninpossessesananti-influenzapotentialthroughitsimmunemodulatoryeffect–ScienceDirecthttps://www.sciencedirect.com/science/article/pii/S1756464619302452)NoneofthepregnantmothersinfectedbyCOVID-19admittedtoZhongnanHospitalofWuhanUniversity,Wuhan,China,developedseverepneumoniaordied;norweretheirbabiesinfectedbyCOVID-19(ClinicalcharacteristicsandintrauterineverticaltransmissionpotentialofCOVID-19infectioninninepregnantwomen:aretrospectivereviewofmedicalrecords–TheLancethttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30360-3/fulltext).Whyismomandbabyprotected?Melatoninsecretioninthethirdtrimesterofpregnancyismorethandoubledcomparedtothefirsttrimester.(VoiculescuSE,ZygouropoulosN,ZahiuCD,ZagreanAM.Roleofmelatonininembryofetaldevelopment.JMedLife.2014;7(4):488–492.)

The death rate of this virus is dependent on age. That is very different from the regular winter flu viruses who are equally dangerous to infants and older people. Recent reports of younger people dying of covid-19 appear to relate to individuals exposed to high levels of WiFi/EMF – which is the major known cause of decreased melatonin levels

The LANCET - Infectious Diseases; March 12, 2020 Real Estimates of Mortality following COVID-19 infection; David Baud; Xiaolong Qi et al

Were-estimatedmortalityratesbydividingthenumberofdeathsonagivendaybythenumberofpatientswithconfirmedCOVID-19infection14daysbefore.Onthisbasis,usingWHOdataonthecumulativenumberofdeathstoMarch1,2020,mortalityrateswouldbe5·6%(95%CI5·4–5·8)forChinaand15·2%(12·5–17·9)outsideofChina.Globalmortalityratesovertimeusinga14-daydelayestimateareshowninthefigure,withacurvethatlevelsofftoarateof5·7%(5·5–5·9),convergingwiththecurrentWHOestimates.Estimateswillincreaseifalongerdelaybetweenonsetofillnessanddeathisconsidered.Arecenttime-delayadjustedestimationindicatesthatmortalityrateofCOVID-19couldbeashighas20%inWuhan,theepicentreoftheoutbreak.

ThesefindingsshowthatthecurrentfiguresmightunderestimatethepotentialthreatofCOVID-19insymptomaticpatients.

FigureGlobalCOVID-19mortalityrates(Feb11toMarch1,2020)

Nitric oxide Inrodentsepsismodels,nitricoxidewasdemonstratedtoinhibitNLRP3activation(NitricoxidesuppressesNLRP-3inflammasomeactivationandprotectsagainstLPS-inducedsepticshockhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567828/)

Nitricoxideproducedinnasalpassagesispartofthedefensesystemagainstbacterialandviralinfections(HighNitricOxideProductioninHumanParanasalSinuses–PubMedhttps://pubmed.ncbi.nlm.nih.gov/7585069-high-nitric-oxide-production-in-human-paranasal-sinuses/?dopt=Abstract)Newbornshavebeenfoundtohaveanextremelyhighlevelofnitricoxideintheirbarelydevelopedparanasalsinuses(Infantnasalnitricoxideovertime:naturalevolutionandimpactofrespiratorytractinfection|EuropeanRespiratorySocietyhttps://erj.ersjournals.com/content/51/6/1702503)

VitCincreasesNO(COVID-19Mutations,Vaccines&NitricOxide–TheVitaminCConnection–EvolutaMente.ithttps://www.evolutamente.it/covid-19-mutations-vaccines-nitric-oxide-the-vitamin-c-connection/

SimpleHummingwhileexhalinginstantlyincreasesthenitricoxideconcentrationinthenasalpassagesandsinuses–theverytissues,wherecovid-19lingersformanydaysbeforeinfectingothertissues(Weitzberg,Eddie,andJonONLundberg."Humminggreatlyincreasesnasalnitricoxide."Americanjournalofrespiratoryandcriticalcaremedicine166.2(2002):144-145.)

ANK:whenevernoonelistenstoyou:hum–topreventortreatCovid-19

StopAngiotensinConvertingEnzymeinhibitors–andSelenium!

SARS-CoV-2infectshostcellsthroughbindingwithACE-2receptors(ReceptorrecognitionbynovelcoronavirusfromWuhan:Ananalysisbasedondecade-longstructuralstudiesofSARS|JournalofVirologyhttps://jvi.asm.org/content/early/2020/01/23/JVI.00127-20)

ACEinhibitors:MedicalACEinhibitorsareusedtotreathypertension.Theyareeffectiveandbelievedtobesafe(Synthesis,CharacterizationandAntioxidantActivityofAngiotensinConvertingEnzymeInhibitors–PubMedhttps://pubmed.ncbi.nlm.nih.gov/21186397/)However,theyareknowntoincreaseexpressionofACE-2andthereforeareknowntoincreasethevirulenceofthevirus.Selenium:Mostintegrativepractitionersbelievethatseleniumisasafetreatmentwithanti-viralproperties(DietarySeleniuminAdjuvantTherapyofViralandBacterialInfectionshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288282/)However,itislittleknown,thatnutritionalseleniummayalsobeaneffectiveinhibitorofangiotensin-convertingenzyme(ACE)(Selenium_Inhibitionofangiotensin-convertingenzymebyselenoneine|SpringerLinkhttps://link.springer.com/article/10.1007/s12562-019-01321-3?fbclid=IwAR2831B7dwtwUy6ehty61SqOr8hlTdlBmRo1geTrcGXOaYnlb4bFXzVIob8)

UsingACEinhibitorseitherthroughmedicationorsupplementsmayriskelevatingCOVID-19infectionanddevelopingsevereorevenfataldiseasecomplications(ArepatientswithhypertensionanddiabetesmellitusatincreasedriskforCOVID-19infection?–TheLancetRespiratoryMedicinehttps://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext?fbclid=IwAR0_oLtc0-5KXduN0-5w6MMsrUyHfo7xDWThnXJEtcPO5S1xPwnzHi8Pw7U#bib4)

The2mainorthomoleculartreatmentoptionsforSARS-Co2(DorisLoh,independentresearcher)

Melatonin:takeatnight,about1to2hoursbeforesleepand2to3hoursAFTERyourlastmeal.D.Lohrecommends50mgatnight.Weuseupto200mgassuppositoryorskinlotion.Youshouldideallyfinisheatingbeforeitisdark.Itisalsoextremelyhelpfulifyoucanloweryourambientlightingatnight,asthelowestamountoflightwilldisruptmelatoninproduction.Melatoninisproducedinallcells,includingmitochondria,notjustinpinealglands.IFyouarediabetic,orhaveinsulinresistance,DONOTTAKEMELATONINbefore3pm.Melatoninisabletosuppressinsulin.•  DAYTIME–40%oftotaldailydose,dividedintosmallequalportionstobetakeneveryTWOHOURS(orally).Ifyouusemelatonintransdermalcream,theabsorptionandserumlevelsevenoutformanyhours.Weapplyupto60mginthemorningandagainataround2-3pmtohairlessbodyareas.

•  NIGHTTIME–60%oftotaldailydose,dividedintotwoportionstaken2-3hoursafterdinner.Thefinaldoseatnightshouldbecompletedby10pm(latest).

VitaminC:IfyouareolderormoresusceptibletoCOVID-19forvariousreasons,yourmaintenancedoseshouldbeonegramperhour,tototal10-18gramsperday,dependingonyourtolerancelevel.Youwillexperienceloosestools,orwhatisknownashittingBowelToleranceifyouhavesaturatedyoursystemwithascorbicacid.•  AscorbicAcidCOVID-19InfectionDosage:1gramevery15to30minutes,dependingonseverityofsymptoms.Increaseto2gramsevery15to30minutesifsymptomsarenotreversedwithin12-24hours.

•  IFyouareinfected,youwillessentiallyhavean‘unlimited’toleranceforascorbicacid.Yourtolerancemayincreaseabove100gramsormore.Thatisnormal.

•  Ifavailable,useintravenousVit.C(7.5grams–50grams/day)on3consecutivedays

Otherthanthehygienemeasuresdiscussedearlierinthispresentation,werecommendadisinfectantthatdoesnotsubstantiallydestroytheprotectiveskinfloraandstillhasenoughanti-viralpotential.IuseisotonicHOCLspray-touseinmyface,eyes,mouthandtorepeatedlyuseonmyhands.Ialsouseitinanoff-labelwaytoinhaleitwithamicronizinginhaler(Omron)onceadayfor15minutesafterseeingpatients,someofwhommightbeincubatingtheinfection.Wenebulizeitintheofficeandhomeregularly.Ialsorecommendanherbalmix(basedonreviewingtheliteratureonnaturalanticorona-viralapproaches).

•  Calendula(Jan,Nelofer,andRiffatJohn."Calendulaofficinalis-animportantmedicinalplantwithpotentialbiologicalproperties."ProceedingsoftheIndianNationalScienceAcademy83.4(2017):769-787)

§  Liquorice("Lickinglatencywithlicorice."TheJournalofclinicalinvestigation115.3(2005):591-593.§  Scutalaria(Skullcap):Wu,Canrong,etal."AnalysisoftherapeutictargetsforSARS-CoV-2anddiscoveryofpotentialdrugsbycomputational

methods."ActaPharmaceuticaSinicaB(2020).§  Rosmary(Wu,Canrong,etal."AnalysisoftherapeutictargetsforSARS-CoV-2anddiscoveryofpotentialdrugsbycomputationalmethods."

ActaPharmaceuticaSinicaB(2020).§  Andrographis(“Broad-spectrumantiviralpropertiesofandrographolide”.ArchivesofVirologyvolume162,pages611–623(2017).

“Andrographolidetreatmentcouldincreasethesurvivalrate,diminishlungpathology,decreasethevirusloadsandtheinflammatorycytokinesexpressioninducedbyinfection.MechanismstudiesshowedtheNF-κBandJAK-STATsignalingpathwaywereinvolvedintheactivityofandrographolide”).AndrographolideinhibitsinfluenzaAvirus-inducedinflammationinamurinemodelthroughNF-κBandJAK-STATsignalingpathway.MicrobesInfect.2017Dec;19(12):605-615.doi:10.1016/j.micinf.2017.08.009.Activityofandrographolideanditsderivativesagainstinfluenzavirusinvivoandinvitro.BiolPharmBull.2009Aug;32(8):1385-91.

§  Artemisiaannua(Li,Shi-you,CongChen,Hai-qingZhang,Hai-yanGuo,HuiWang,LinWang,XiangZhangetal."IdentificationofnaturalcompoundswithantiviralactivitiesagainstSARS-associatedcoronavirus."Antiviralresearch67,no.1(2005):18-23.)

§  Dandelion(Taraxasterol)(INVIVOANTI-INFLAMMATORYEFFECTSOFTARAXASTEROLAGAINSTANIMALMODELS.AfrJTraditComplementAlternMed.2016Nov23;14(1):43-51.doi:10.21010/ajtcam.v14i1.6.)

Isuggestthefollowing:.Put100mlcleanwaterinablenderandaddtheweeklydoseofVitCpowder.Thenaddtheherbalcomposition“Andrographis+”(upto12dropperful/day.Calculatetheweeklytotal).Add2tablespoonsofMicrophosandblendforseveralminutes.Putthisliposomalmixinaglassandkeepinthefridge.Estimateoneseventhoftheamount,putitinaseparateglassanddrinkthecontentovertheday.Youmayuseadditional“Andrographis+”tincturefrequently-dependingonpossiblecurrentorpastexposures.Alwayshaveabinderonboardandusetheionicfootbathtokeeptheemuntories(exitroutes)free.

Almost common sense: •  UseyourHOCLinhalerfrequentlyduringtheday.Alsosprayyoureyes,insideofyourmouth.UseafoggerinyourhomeoncedailytocreateHOCLmistintheair,settlingonallsurfaces.TakeHOCLwithyouanduseinrestaurants,workplace,coffeeshop,dentist’soffice,etc.

•  UsePropolissprayinsideyourmouthalternatingwithHOCL.Usepropolisvaporizerineachroomofyourhomeforseveralhours/day.AlternatewithHOCL.Changeyourclothesafterbeingoutsideanddon’treusefor72hours.Keepyourshoesoutside.

•  UseVitCeveryhour.•  KeepyourVitDlevelhighnormal•  Food:Duringinfection,rest,drinkplentyofpurifiedwater.Youmayloseyourappetite.Donotforceyourselftoeatifyouarenothungry.Calorierestrictioninitiatesmitophagyandautophagy,whichwillfacilitatehealing.

•  DonotuseNSAIDS(ibuprofenetc.)(”Nonsteroidalanti-inflammatorydrugwithoutantibioticsforacuteviralinfectionincreasestheempyemariskinchildren:amatchedcase-controlstudy”.TheJournalofpediatrics,175,47-53(2016);Bourgeois,M.,etal)

A quick look to the dark side Pradhan,Prashant,etal."Uncannysimilarityofuniqueinsertsinthe2019-nCoVspikeproteintoHIV-1gp120andGag."bioRxiv(2020).DK:Thisarticlewaswithdrawnrecently,whichmakesmesuspicious….Irrefutable:Thecoronaviruswasengineeredbyscientistsinalabusingwelldocumentedgeneticengineeringvectorsthatleavebehinda“fingerprint”Monday,February03,2020by:MikeAdams.Mikeisoftencorrect…..JournalofGeneralVirology;Volume92,Issue8,2011“TheADP-ribose-1″-monophosphatasedomainsofsevereacuterespiratorysyndromecoronavirusandhumancoronavirus229Emediateresistancetoantiviralinterferonresponses”ThomasKuri,KlaraK.Eriksson,etal.Abstract:Severalplus-strandRNAvirusesencodeproteinscontainingmacrodomains.ThesedomainspossessADP-ribose-1″-phosphatase(ADRP)activityand/orbindpoly(ADP-ribose),poly(A)orpoly(G).Therelevanceoftheseactivitiesinthevirallifecyclehasnotyetbeenresolved.Here,wereportthatgeneticallyengineeredmutantsofsevereacuterespiratorysyndromecoronavirus(SARS-CoV)andhumancoronavirus229E(HCoV-229E)expressingADRP-deficientmacrodomainsdisplayedanincreasedsensitivitytotheantiviraleffectofalphainterferoncomparedwiththeirwild-typecounterparts.Thedatasuggestthatmacrodomain-associatedADRPactivitiesmayhavearoleinviralescapefromtheinnateimmuneresponsesofthehost.ThispapershowsthatpoorCoronaisoneofthemostexperimented-onformsoflife–andcouldeasilybemisusedfordestructivepurposes

Outlook Thereareseveralwaystodealwithaviralepidemic:1.  Preventtheherd-infectionbymassivesocialisolation(consequences:nohealthcare,nofood,no

deliveries,noelectricity,nowater–alldependonpeopleshowingupatwork)

2.  Preventtheinfectionwithavaccine(thetrackrecordofsuccessisfairlypoor–lookattheinfluenzarecord.Vaccinesaretypicallyonthemarketwhentheillnessisalmostgone)

3.  Preventtheinfectionbyusingnon-toxicprophylactictreatment(anexampleisoutlinedinthistalk)4.  Creatingtrueherd-immunity:Lettheinfectionhappenandsupportthesystemduringthe

illnesswithnon-toxicbiologicalmeasures(wehavedecadesofexperiencedoingthatwiththechickenpoxvirus-bygettingchildrentogetherwithaninfectedchildandenjoyinglonglastingimmunityaftertheillness)

ThefinancialandsocialconsequencesofthecurrentCovid-19outbreakareastronomical.Ibelieveifthecurrentknowledgeaboutnon-toxicanti-viralstrategiesisusedtogetherwithcommonsensepreventivemeasureswewillgetthroughthisinafewmonths.Mostvirusesadaptandmutatetolivewithus-insteadofdyingwithus-andtheillnessbecomesmilderandlessaggressive–intime.Therealunknownisif–orhowmuch-humanhandsareinvolvedinproducingthisvirusandwhatintentmightbeworkedintoit.Iamwishingyouwellandhopeforallofusthatthisblowsoverwithoutanyfurtherlossoflife.