Posted on Authorea 20 Apr 2020 | CC BY 4.0 | https://doi.org/10.22541/au.158739631.11698779 | This a preprint and has not been peer reviewed. Data may be preliminary. ueosptnilcniae frproal rg htcnpoieasnritceeti potentially in 2019-nCoV effect against synergistic progression their a and provide urgently about candidates community can are Drug research that scientific outbreak not the drugs 2019-nCoV still to repurposable information are the 2019-nCoV/SARS-CoV-2. accumulate of drugs treating for an and candidates offer approaches vaccines will potential discoveries successful review numerous This but drug production 2019-nCoV, [10]. treatment and vaccine [9] the of prevention needed on manual treat working Active the and are potential without prevent the but groups available. to with world research repurposing and the international before drug of and attention seen and national the been a [8].Several never gained generate management to has it capacity rapidly, that and possible and syndrome protein the extensively respiratory inducing restrict specific spread a which (S this for to is MERS, protein immunogenic it responsible and Spike how the [7].Since SARS COVID-19 factor on quickly to the on antigenic studies vaccine comparisons knowing protein key no surrogate to beyond S the are addition go in there is can 2019-nCoV, [5]. MN908947.3), and For cycle (GenBank: entry [6]. sequences life host virus protein) COVID-19 the in and of the role protein response starts immune critical S and the in and a domain SARS-CoV fusion plays receptor-binding (2019- for membrane membrane the coronavirus (ACE2) between mediates viral novel Binding 2 receptor, the receptor. SARS-CoV, Enzyme cellular host-entry to Converting the its target Compared Angiotensin as and ACE2 [4]. protein) as, uses (S MERS-CoV such nCoV) protein for infection spike surface, SARS (DPP4) the CoV 210 cell Peptidase-4 in endemic in located [3]. host Dipeptidyl [2]. include domain Syndrome) assessment the confirmed binding which Respiratory under receptor on been endemics, the East remains receptor of had lethal (Middle COVID-19 interaction MERS the in cases of with and rate resulted 1,865,979 begins Syndrome) fatality Approximately, had outbreak, Respiratory The coronavirus Acute COVID-19 [1]. human (Severe 2020. the 2019; (WHO) of 13, 31, Organization of infections April December Health result However, till on World China, territories a the in and as by Province countries died Hubei 2020 Wuhan, 12, people in January 115,224 occurred on cases pneumonia ”COVID-19” viral named of type new practices. A clinical potential lead to and trials prospective repurposable Introduction to in of community drugs number research proposed a study international the of the of the identification efficacy allow Herein, rapid the preferentially validate offer and against to will outbreak. 2019-nCoV effective findings, review targeting be 2019-nCoV the This to combinations evaluate human the prove drug trials. could of against potential clinical which and drugs) cause discovery of with another drugs stages world, drug the with different the integrated fast as under over or There are and identified alone all (either 2019-nCoV, guidance. intervention people 2019; drugs procurement active infected of the 31, of candidates without for numerous arose cases December provides need but reported on prominence immediate and worldwide China, achieved death an rapidly, of in and is toll widely cases spread heavy to pneumonia a potential took viral the “COVID-19,” of as type labeled new coronavirus, of emergence The Abstract 2020 28, April 1 MIna Fahmida COVID-19 Battling Clinical for Registered Trials Several Underway Candidates Drug Potential nvriyo Rajshahi of University 1 d Rahman Md. , 1 au Das Sabuj , 1 uo Karmakar Sumon , 1 1 n uai Billah Mutasim and , 1 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. ciiywihcnsnritclyices t nvv niia mat olwn h icvr nCiaof China in discovery the of Following immune-modulating glycosylation an impact. the has antiviral with vivo chloroquine interfering activity, in as antiviral its well virus its as increase the to fusion, synergistically with addition cell can infection In / which block activity virus to [25]. for known receptors needed is cell pH Chloroquine SARS-CoV endosomal [23-24]. the drug identified growing antiviral been by recently wide-spectrum has potential medication, disease a autoimmune as and a anti-malarial used as commonly research a ongoing Chloroquine, [16-22]. of derivatives focus synthetic it the improved effects, for be derived side blueprint to extreme Ribavirin Chloroquine continues a to it as a due Nevertheless, or candidus, but drug, trials. properties 2019-nCoV clinical Streptomyces anti-cancer human possible in and in antiviral, effective present antibiotic, not product was has It natural analog. a nucleoside is (Pyrazomycin) COVID-19.Pyrazofurin to resistance be 109.50 to = prove mightPyrazofurin (EC50) may uncertain anaemia results, Concentration is as preliminary Effective 2019-nCoV such to against (Half- according effects, potency as and, sufficient side such offer has concentrations could (CC50) it high it Concentration but in whether and MERS, Ribavirin, [12] and syncytial doses [15]. respiratory SARS high and with at (HCV) patients severe coronavirus prove in Human evaluated treating nucleoside. for (RSV), approved antiviral derivative virus this guanine of a efficacy is the Ribavirin test to 2019-nCoV against screened Ribavirin be to studies vivo in further 1] lhuh C0vleo aiiai nVr 6clswsa iha 67 as high as was 61.88 cells = E6 (EC50 Vero in in 2019-nCoV Favipiravir of (ChiCTR2000029544) infection of endonuclease) viral value cap-dependent EC50 the Although, targeting tri- [13]. inhibitor randomized in influenza recruited approved interferon- being (an plus favipiravir are study,marboxil of 2019-nCoV recent efficacy with a RNA the Patients evaluate adding of to enterovirus, [10]. als and 2019-nCoV polymerase norovirus against chikungunya, RNA activity fever, its RNA-dependent yellow reported Ebola, the influenza, inhibits as such analogue,effectively China. viruses guanine by established a immune trial (T-705), is clinical Favipiravir which of cancer), III liver human Phase of the cells also in Favipiravir Remdesivir (Huh-7 is that line it currently, suggested cell data human and Preliminary a 2019-nCoV in to [12]. infection SI virus high blocked showed effectively and infection virus blocked effectively 20m ndy1ad10m nediyfr9dy) ihetmtdcmlto ae nArl22 [11]. 2020 April in dates completion estimated with days), 9 for daily once 0.77 mg = 100 2019- (EC50 and with patients Remdesivir 2019-nCoV, 1 Remdesivir in Notably, intravenous day inhibited evaluate trials on to been as Remdesivir February mg 6, early has that in January (200 and initiated in confirmed were SARS, remdesivir NCT04257656) research intravenous and and receiving (NCT04252664 recent MERS nCoV after A recovered 0.77 - get = as to EC50 such trial. reported of viruses, clinical concentrations broad- RNA in has a tested against Remdesivir in when models transcriptase. Ebola reverse animal similar HIV for and structure of checked cultures chemical inhibitor cell a approved with in an alafenamide, effects prodrug tenofovir phosphoramidate novo of derivative that adenine de to an to is compared (GS-5734) cost Remdesivir against the screened reduce drugs and of candidates Remdesivir time potential the of cut information accumulated could the drugs 2019-nCoV/SARS-CoV-2. transmission, approach, existing is Following rapid from development successful representing discovery. its no drug repurposing, drug are to Drug active there due However, SARS-CoV-2. an death priority. / urgent of as 2019-nCoV very toll a for therefore targeted heavy is currently a 2019-nCoV drugs causing against drugs pandemic, of ongoing discovery the labelled has 2019-nCoV As > 400 μ ,SlciiyIdx(SI) Index Selectivity M, μ ;CC50 M; μ μ ,CC50 M, nVr 6cls[0 n Sptetwt 09no was 2019-nCoV with patient US One [10] cells E6 Vero in M > 100 2 α μ CiT20090)adfvprvrpu baloxavir- plus favipiravir and (ChiCTR2000029600) ;SI M; > > 400 .5 a eddt iiievrlifcin[10] infection viral minimize to needed was 3.65) μ > ,SI M, 2.7 tlwmcooa concentration, low-micromolar at 129.87) > .6 ocnrtos[4 suggesting [14] concentrations 6.46) μ .I a eotdt reduce to reported was It M. μ ,Half- M, Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. bpoe sapoincai-eie o-tria niiflmaoydu NAD,adi nw ob the be to known is and (NSAID), of drug anti-inflammatory use non-steroidal acid-derived the propionic anti- link a is non- to Ibuprofen of evidences use [35]. clinical the agency insufficient on the statement are to Ibuprofen according a There symptoms, released 2019-nCoV. COVID-19 has have worsening with (FDA) NSAIDs admission in patients Administration requiring NSAIDs [34]. patients in Drug site to and (NSAIDS) treatment one Food antibiotic than drugs effective The compli- more prescribing chronic of to in hospital. effusions, infection rates delays to pleural with of higher associated suppuration pneumonia, with been or complicated associated also spread including are abscess, infections, NSAIDs peritonsillary tract that disease, coronavirus respiratory indicates of following studies case-control cations outbreak of latest analysis the Recent that found (NSAIDs) be shown Researchers could Drugs been therefore, Anti-inflammatory [33]. is [32]. also Non-Steroidal studies and has body further cells suggesting epithelial It human 2019-nCoV, alveolar the human against invading lung. screened of is the invasion significantly SARS-CoV-2) displayed (2019-nCoV, in SARS-CoV mice pneumonia expression for protein-treated SARS-spike ACE2 receptors wild-type reduced key recombinant the or SARS-CoV-infected of that one is infection” ACE2 (CoVID-19) (ACE2) pneumonia 2 other coronavirus and Enzyme novel The clinicaltrials.gov) Converting on on Angiotensin ARBs clinicaltrials.gov. withdrawn treatment / [31]. on as a March) ACEIs listed identified 2 as of also on but effects (rhACE2) February (registered is the 2 was 21 on it enzyme China” on research recruiting; angiotensin-converting in ”Clinical (registered human be infection patients” ”Recombinant to COVID-19 2019-nCoV Clinical characteristics stated recruiting: for ”Clinical International with is entitled not the treatment first, and are WHO, 21 ACE1 The February two of the without China. 12 (as of moment and in on website way the with published ICTRP under At patients or the [30]. between planned on 19 SARS-CoV- being COVID difference listed coronavirus as as of are Portal, known symptoms trials Registry infection the Trials related candesartan the of of three as treatment an- cause and such 2020) and prevention the March ARBs), ramipril, the 2019-nCoV), or in as and blockers use known enalapril of 2(also angiotensin as be as could such known valsartan, inhibitors), and (colloquially (ACE-1 antagonists inhibitors receptor 1 giotensin Enzyme Conversion treatment Angiotensin the (ACE1) in 1 option Enzyme first Converting the inclined Angiotensin be more therefore are as researchers will same as so which the effective similar, periods, SARS-CoV-2. generally as is long is of molecules is for two viruses HCQ potent hydroxychloroquine these on seven whether administer of Hydroxychloroquine a 2020, lacks mechanism to [29]. February (http:/www.chictr.org.cn) be action still infection the 23 Registry evidence may SARS-CoV-2 Trial because of experimental of HCQ chloroquine Clinical The As treatment Chinese that the diagnosis. the [28]. in idea COVID-19 in animals CQ up for the listed conjure in HCQ been immune-modulator, to use CQ have and to simple trials than is base clinical toxic infection of weak as (˜40%) registries SARS-CoV-2 a such treating less structures diseases as chemical for much autoimmune similar by serve share candidate of be HCQ 1946 to treatment and CQ to the in mechanisms Since for shown synthesized and available arthritis. rheumatoid was commonly first and now erythematosus and was lupus is systemic CQ HCQ (CQ), significantly, into Chloroquine More group [13]. of hydroxyl derivative a a inserting sulfate, (HCQ) Hydroxychloroquine [27]. (ChiCTR2000029609) cells Hydroxychloroquine trial E6 1.13 open-label Vero = an (EC50 of in 2019-nCoV concentrations tested against effective is activity inhibitory 90% shows and modulator, 50% immune SARS-CoV-2, against activity (EC50=1,13 chloroquine vitro in μ n EC90=6,90 and M μ )wr icvrddrn utr et[2.Clrqie nauthorized an Chloroquine, tests[12]. culture during discovered were M) 3 μ nVr 6cls 2]and [26] cells) E6 Vero in M Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. aur osuyRtnvradTC301 toHVpoes niio)i lncltil o ramn of treatment to for native in trials authorities both clinical in Chinese are inhibitor) the who protease to patients HIV applied (two for Pharma, less TMC-310911 therapy Ascletis and be suitable Hangzhou-based Ritonavir may study The potentially and to PI. a strains, January with multi-PI-resistant it experienced including demonstrated making and has strains, resistance, care TMC-310911 HIV-1 produce darunavir. of investi- the to been number to has likely similar a that structurally against is (PI) and activity inhibitor infections protease potential HIV-1 investigational novel in use a for is gated ASC-09) risk as the known (also reduce TMC-310911 and screened illness, being and is [40]. fever failure).Oseltamivir trial shown TMC-310911 of clinical respiratory have undergoing symptoms studies and is observational of pneumonia and and length (including 2019-nCoV trials the complications against clinical replication, shorten health viral from can other budding, data cell therapy of CDC, host antiviral the (including inhibits early to A the which of According that surface, virus function virus the influenza [37]. inhibiting the infectivity prophylaxis by on function and and located antiviral treat its enzyme exercises to neuraminidase Oseltamivir viral used infection. agent B [15]. and [12] antiviral H1N1) drug neuraminidase pandemic this a of is efficacy antiviral Oseltamivir the determine to trials potentiality clinical the Oseltamivir needs has thus, Neitazoxanide therapy, and diarrhea including 2019-nCoV for viruses, inhibit Authorized of to concentrations, infection. range micromolar 2019-nCoV low wide at against a 2.12 2019-nCoV, suggested against = to EC50 resistance capacity - be antiviral as to an such reported with coronaviruses, agent animal and antiprotozoal human commercial with a is infection It in step [39]. first inhibitor the SARS-CoV-2 will proteins, a recently Nitazoxanide Nafamostat was surface as Tokyo, which group (Foypan), cell of mesylate German host University Camostat a by the the by provided with at concentration described the envelope researchers of the virus one-tenth at per the SARS-CoV-2 As of fusion found [10]. was the studies fusion, 22,50 prevent membrane further = obstructs for EC50 that in suggested inhibitor tested MERS- rate, when powerful infection a is 2019-nCoV properties, anti-cancer It to and inhibitive pancreatitis. antiviral contains acute that treat inhibitor, to protease used serine synthetic a mesylate, Nafamostat caused mesylate avail- COVID-19 for currently Nafamostat virus agent with Hantaan prophylactic conjunction and Reovirus, [37]. treatment in infections virus, potential investigated a SARS-CoV2 Chikungunya being as by currently virus, therapies enveloped is HIV C exert of investigational Umifenovir and Lassa and number to [38]. able B disease, a B5 Foot-and-mouth Umifenovir Hepatitis for virus virus, simplex, use of Coxsackie Zika its and Herpes Flavivirus, ability into virus, including work The viruses, Ebola extensive DNA virus, to in- and prophylaxis. led RNA for and has non-enveloped used mechanisms treatment and agent, several infections host-targeting across effects / respiratory antiviral antiviral other active and dual-acting fluenza hydrophobic, indole-based, an analysis. Umifenovir, its further and for screened [35], R-enantiomer be could the the Umifenovir and than that unclear activity particular, is pharmacological in drugs. 2019-nCoV greater available proposed; against commonly generating first the ability the is on of action was It the mixture capable drug It through racemic administered. is this vivo arthritis. a its S-enantiomer in and rheumatoid when as S-enantiomer against alpha-methylacyl-CoA, given 1961, the 1974 racemase is to in in of interconversion ibuprofen patented USA comprehensive The the eventually undergoes in [36]. R-enantiomer, was and counter The Ibuprofen 1969 the in over aspirin. available UK of NSAID the 1960, in alternative in introduced discovered safer first originally a was acid, propionic for 2-(4-isobutylphenyl) looking is Ibuprofen while of Theformula propionic. first μ ;CC50 M; > 35.53 μ ;SI M; > 67 1] ute nvv vlaino hsmdcto is medication this of evaluation vivo in Further [10]. 16.76 4 μ ,CC50 M, > 100 μ ,SI M, > ,4concentration 4,44 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. h ia neto n ol ute eeaie saCVD1 rg[4 [15]. analog [14] nucleoside drug High COVID-19 a 2019-nCoV. as against examined tested be Disulfiram further drugs could the and of infection Sim- 95.96 viral one Herpes = the a (EC50 is as Penciclovir inhibitor, functions of activity, DNA concentrations antiviral (HSV) containing derivative, Virus guanine plex acyclic synthetic a Penciclovir, may capabilities bio-containment sufficient effectiveness [37]. with Penciclovir its [15] facilities [13] that and 2019-nCoV viruses, are subjects RNA against possibilities many Galidesivir healthy against and screen studies MERS2, in preclinical and in protection activity SARS antiviral its like demonstrated currently has examining is and fever, (HCV), studies yellow coronavirus against human clinical for developed early-stage originally undergoing analog adverse adenosine an several (BCX4430), to Galidesivir due needed be be should may nucleoside [37]. assessment therapy Galidesivir a therapies Their of interferon and discontinuation subcutaneous unclear. interferon or with is reduction associated pegylated however effects plus dose a 2019-nCoV interferon and Whether against pegylated monitored synergistically of closely 2019-nCoV, combination work (ChiCTR2000029387). with anti-HCV could infected initiated approved compound patients an been in as Human have responses and such antiviral Ribavirin, (HBV) interferons, innate virus involving induce B to studies Hepatitis used of and treatment be the may for (HCV), approved Coronavirus alfa-2b, and alfa-2a Interferon re- Pegylated was 10-30 Arbidol alfa-2b of 2019-nCoV and range process. [45]. with alfa-2a patients concentration in infections Interferon in are a initiated influenza studies was at treat further Arbidol 2019-nCoV of and to against trial [46] China clinical vitro (ChiCTR2000029573) controlled and multicenter in randomized Russia successful a in China, been used have drug to antiviral ported an is Pneumonia Arbidol 2019- and against Diagnosis influenza screened of possibly for version be used current Arbidol could vastly the and infections, in [44] tract COVID-19 indicated proven by [43]. respiratory also and Caused nCoV is upper herbs Infection medicinal medication of 2019-nCoV eight This of treatment of Treatment the total China. a for in of effective diagnosis composed clinically (TCM), be Medicine Chinese to Traditional a is SFJDC regimen [44]. Diagnosis 5) antivirus (SFJDC) of form (version recommended Capsule latest 2019-nCoV ShuFengJieDu the a by in currently China Caused and of is Pneumonia Lopinavir Republic People’s Ritonavir of that the Treatment and of revealed and SARS-CoV Commission Lopinavir was among Health non-randomized National of outcomes) It the clinical combination by a approved adverse patients. The in (less to SARS benefit correlated suspected [43]. of clinical patients initially significant be outcomes with were clinical seemedto associated improved Ritonavir were and with Ritonavir and HIV protease 2, Lopinavir study 3-chymotrypsin-like trial to MERS Ritonavir. open-label initiated and and were Lopinavir ChiCTR2000029539) SARS (e.g., as inhibit trials such clinical inhibitors 2019-nCoV, protease with infected patients In [41][42]. other 2019-nCoV with for Ritonavir combination treatment with and in potential conjunction Lopinavir investigated, a in as being SARS-CoV-2 antivirals, currently by and is caused therapies antivirals.TMC-310911 COVID-19 HIV and for therapies therapy HIV possible other a as TMC-310911 COVID-19. μ ,CC50 M, 5 > 400 μ ,SI M, > .7 1]wr eddt reduce to needed were [10] 4.17) μ 4] In [43]. M Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. al :OgigCiia raso oeta rg o h ramn fCOVID-19 of Treatment the for Drugs Antimalarials) Potential and drugs of (Antivirals the Trials of Clinical efficacy Ongoing the evaluate 1: to are Table globally and conducted progress for being (Table-1) cure under currently COVID-19 potential are are against a trials vitro trials clinical as in Clinical registered studied to Several being 2020. [52]. Due August is COVID-19 in Darunavir [54]. end for infection, to [53] this is pharmacokinetics responsible scheduled fight the (CYP3A) Darunavir coronavirus to enhance P450 the ability to currently treatment. cytochrome SARS-CoV-2, its booster is AIDS inhibiting a supports mixture in by is that (FDA) a darunavir ritonavir, evidence Such Administration like of cobicistat, Drug pharmacodynamics (50). and and and inhibitor NCT04252274 Food concentration protease used number States a HIV be trial United another will at in cobicistat, strain, the with pneumonia new by conjunction COVID-19 the approved in Darunavir, of with research replication patients preliminary successful. inhibit to in be effectively according may micromolar, can 2019-nCoV 300 Darunavir against of that Darunavir evaluating shown that have (SPHCC) indicated studies have reassessed. Center authorities be Clinical can Chinese and Health The successful Public been Shanghai not has the it Darunavir studies at that dependent II shown phase cobicistat trial has in / COVID-19 randomized regimen atazanavir ritonavir for a / An Cobicistat integrase atazanavir cobicistat However, atazanavir, an [52]. trials, with to substrate) I combination comparable [50]. Phase protection test in and In ritonavir CYP3A efficacy to effects. (a provided enhancer regimen side midazolam therapeutic of or profile comparable elvitegravir, reduced a inhibitor a increasing be dosing without and to (ARVs) daily outcomes shown exposure (once antiretroviral patient was darunavir systemic improved or Growing for atazanavir infection. allows of HIV-1 dose still of exposure which care systemic the function, increase in antiviral to regimen) agents no antiretroviral with other enhancer with than pharmacokinetic specifically more recent although a CYP3A, inhibits is GS-9350) (formerly Cobicistat but trials, treatment I 2019-nCoV phase the in prevention for association Cobicistat 2 HIV re-evaluated is an for enzyme be which enema conversion such should HIV or inhibitors Interestingly, I molecules gel to spike angiotensin prevention. a GRFT of compared human surface. or as mechanisms three the number studied delivery S to lower been and of the has glycoprotein efficacy a total Griffithsin on the S dose, A SARS-CoV glycans [49]. a cell of high host in binding protein). (ACE2) of affinity the (S number restrict high lower glycoprotein not very GRFT the does the with cells. to S of control due on the surface toxicity presumably may binding the limited inhibited of and SARS-CoVreplicationand GRFT with to cells, capable EC50 inhibit nature, glycans 76 nanomolar are to Vero glycosylated low with in shown highly a particular, bind infectionwith been is In - can has it [49]. SARS [48] GRFT of to viruses strains coronaviridae due protein. various other cytotoxicity, protein spike as low spike well coronavirus has as coronavirus of cytopathicity, Griffithsin oligosaccha- any role to glycoprotein2. with glycoproteins the spike viral interfere impede various SARS-CoV to of and surface likely 120 the is on glycoprotein binds HIV algae, including red rides from derived lectin a Griffithsin, it outbreak. However, SARS-CoV-2 by as, / 2019-nCoV it. well [37][47].9-nCoV against of bio-containment screened as Griffithsin evidence of 3-chymotrypsin-like, be capabilities clinical possibly the sufficient no could inhibit have inhibit Disulfiram is effectively that to although, there facilities could 2019-nCoV, reported but inhibitors of been cultures protease proteases has cell papain-like HIV dependence, in whether alcohol protease debatable, of papain-like is treatment SARS the and for MERS medication approved an Disulfiram, nvitro in 6 ioai 5] oiitti niae nconjunction in indicated is Cobicistat [51]. Ritonavir nvitro In cell Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ICTPR) ChiCTR2000029548 (ICTPR) ChiCTR2000029544 (ICTPR) ChiCTR2000029600 (ClinicalTrials.gov) NCT04315948 (ClinicalTrials.gov) NCT04257656 (ClinicalTrials.gov) NCT04252664 (EU-CTR) 2020-000842-32 (EU-CTR) 2020-000841-15 (ClinicalTrials.gov) NCT04280705 Antiviral (ClinicalTrials.gov NCT04292730 Antiviral (ClinicalTrials.gov) NCT04292899 Antiviral (ClinicalTrials.gov) NCT04302766 Antiviral Antiviral (EU-CTR) 2020-000936-23 Antiviral (Registry) No. ID trial Clinical favipiravir A Arm favipiravir A Arm atomisation alpha interferon and favipiravir A Arm treatment B remdesivir A Arm remdesivir A Arm remdesivir A Arm treatment B remdesivir A Arm treatment B remdesivir A Arm remdesivir A Arm treatment standard B: Arm remdesivir A Arm treatment standard B: Arm remdesivir A Arm treatment standard B: Arm remdesivir A Arm remdesivir 1a beta interferon B Arm lopinavir/ritonavir A Arm infection prevent to Intervention standard : standard : standard : r C Arm : : : : : : : : : : : : : : : Arm Arm Arm 0YsNtrcutn China China recruiting Not recruiting Not China Recruiting Yes France Yes China Recruiting China No 30 Recruiting 30 Recruiting Worldwide Yes Yes 90 Recruiting Worldwide Yes South & USA 3100 Recruiting Yes 453 Asia Recruiting & USA 308 Yes Asia Recruiting & USA Yes 600 Recruiting Yes 400 394 USA Yes France 600 Available Recruiting 400 Unspecified Unspecified Yes 3000 size Participant 7 admzdSau Country Status Randomized (Pharma.) Koria Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ClinicalTrials.gov) NCT04276688 (ICTPR) ChiCTR2000030922 (ClinicalTrials.gov) NCT04303299 (ICTPR) ChiCTR2000029996 (ICTPR) jRCTs041190120 JPRN- (ClinicalTrials.gov) NCT04310228 (ICTPR) ChiCTR2000030987 (ICTPR) ChiCTR2000030254 (ICTPR) ChiCTR2000030113 (ClinicalTrials.gov) NCT04273763 ea1b beta interferon + lopinavir/ritonavir + ribavirin A Arm ribavirin and umifenovir 2a alpha interferon and ribavirin A Arm favipiravir and lopinavir/ritonavir A: Arm favipiravir C favipiravir B favipiravir low-dose A Arm 6–15) (Day favipiravir delayed 1–10) (Day favipiravir immediate A Arm favipiravir B Arm tocilizumab and favipiravir A Arm favipiravir B Arm chloroquine and favipiravir A Arm favipiravir A Arm favipiravir A Arm a2b interferon umifenovir, (mucolytic), bromhexine and favipiravir A Arm medium-dose : high-dose : r B Arm r B Arm : : : : : : : : : : : Arm Arm : : 0YsRcutn ogKong Hong Recruiting China Yes Recruiting Thailand recruiting Not Yes 70 China Yes Recruiting 30 Japan 80 Yes Recruiting China 60 Recruiting Yes China China Recruiting China Yes 86 Recruiting Recruiting Yes China 150 Yes Yes Recruiting 150 240 Yes 20 60 8 hr.Group) Pharm. (WanBangDe Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ICTPR IRCT20100228003449N29 (ICTPR) IRCT20100228003449N28 (ICTPR) IRCT20100228003449N27 (ClinicalTrials.gov) NCT04303299 (ICTPR) ChiCTR2000029609 (ICTPR) ChiCTR2000029387 lopinavir/ritonavir and ychloroquine B Arm vir/ledipasvir sofosbu- and ritonavir, lopinavir/ ychloroquine, A Arm lopinavir/ritonavir and droxychloroquine 1a beta interferon and ritonavir, lopinavir/ ychloroquine, A Arm lopinavir/ritonavir and droxychloroquine 1b beta interferon and ritonavir, lopinavir/ ychloroquine, A Arm chloroquine and oseltamivir A Arm chloroquine (severe): C Arm chloroquine + lopinavir/ritonavir moderate): (mild– B Arm chloroquine moderate): (mild– A Arm alpha-1b interferon and lopinavir/ritonavir, B alpha-1b interferon and ribavirin A Arm ribavirin, : r B Arm r B Arm hydrox- : hydrox- : hydrox- : hydrox- : : : Arm hy- : hy- : 0YsRcutn Iran Recruiting Iran Yes Recruiting 50 Iran Yes Recruiting Thailand recruiting Not 30 Yes Yes China 30 Recruiting 80 No China Recruiting 205 Unspecified 108 9 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ClinicalTrials.gov) NCT04252885 (ICTPR) ChiCTR2000030922 (ICTPR) ChiCTR2000030254 (ClinicalTrials.gov) NCT04273763 (ClinicalTrials.gov) NCT04315948 (ICTPR) jRCTs031190227 JPRN- (unspecified) treatment basic + umifenovir B Arm (unspecified) treatment basic + lopinavir/ritonavir A Arm ribavirin and umifenovir B Arm ribavirin and 2a alpha interferon A Arm B favipiravir A Arm a2b interferon and umifenovir B Arm favipiravir and a2b, interferon umifenovir, (mucolytic), bromhexine A Arm treatment standard quine hydroxychloro- 1a beta interferon and lopinavir/ritonavir C Arm lopinavir/ritonavir B remdesivir A Arm hydroxychloroquine and lopinavir/ritonavir A Arm umifenovir : : r E Arm : : : : : : : : : : r D Arm Arm Arm : : 2 e eriigChina Recruiting China China Recruiting Yes Recruiting Yes 125 China Yes Recruiting 30 240 Yes France 60 Recruiting Japan recruiting Yes Not Unspecified 3100 50 10 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ClinicalTrials.gov) NCT04261270 (ICTPR) ChiCTR2000029592 (ICTPR) ChiCTR2000029993 (ClinicalTrials.gov) NCT04255017 (ClinicalTrials.gov) NCT04254874 (ICTPR) ChiCTR2000029621 (ICTPR) ChiCTR2000029573 C oseltamivir and ritonavir B Arm oseltamivir and A Arm umifenovir B umifenovir A Arm treatment standard B Arm capsule Liushen and umifenovir A Arm lopinavir/ritonavir C Arm B umifenovir A Arm 2b alpha interferon pegylated and B umifenovir A Arm treatment B umifenovir A Arm umifenovir and novaferon F Arm lopinavir/ritonavir E umifenovir D Arm lopinavir/ritonavir C Arm umifenovir and B umifenovir A Arm oaeo and novaferon : without : oseltamivir : umifenovir : standard : Novaferon : oseltamivir : : : : : : ASC09 : : : : : : : : Arm Arm Arm Arm Arm Arm Arm 0YsRcutn China Recruiting China Yes China recruiting Not Recruiting Unspecified China 60 Recruiting Yes 100 China Yes Recruiting China 40 Recruiting Yes 400 Yes 100 China 380 recruiting Not Yes 480 11 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ICTPR) ChiCTR2000029541 (ICTPR) ChiCTR2000029548 (ClinicalTrials.gov) NCT04261907 (ICTPR) ChiCTR2000029600 (ICTPR) ChiCTR2000029609 (ClinicalTrials.gov) NCT04303299 thymosin C Arm thymosin and lopinavir/ritonavir B Arm thymosin and darunavir/cobicistat A Arm lopinavir/ritonavir C Arm B marboxil baloxavir A Arm lopinavir/ritonavir B Arm ASC09/ritonavir A Arm atomisation alpha interferon and lopinavir/ritonavir B Arm atomisation alpha interferon A Arm lopinavir/ritonavir (severe): C Arm chloroquine + lopinavir/ritonavir moderate): (mild– B Arm lopinavir/ritonavir moderate): (mild– A Arm oseltamivir and lopinavir/ritonavir D Arm oseltamivir and lopinavir/ritonavir C Arm favipiravir and lopinavir/ritonavir B Arm chloroquine and oseltamivir A Arm favipiravir : : : : : : : : : : : : : : Arm 0 e o eriigChina recruiting Not China recruiting Not Yes (Ascletis China Recruiting Yes 100 China Yes Recruiting 30 160 No China Recruiting 90 Yes Thailand recruiting Not 205 Yes 80 12 Pharm) Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ICTPR) ChiCTR2000030166 (ICTPR) ChiCTR2000029468 (EU-CTR) 2020-001113-21 (ICTPR) ChiCTR2000030535 (ClinicalTrials.gov) NCT04291729 lh 2b alpha interferon and lopinavir/ritonavir granules Bai-Du-Yin Qing-Wen and 2b alpha interferon and lopinavir/ritonavir A Arm lopinavir/ritonavir B Arm itabine/tenofovir emtric- and lopinavir/ritonavir A Arm placebo 1a beta interferon C Arm dexamethasone B Arm lopinavir/ritonavir A Arm lopinavir and inhalation alpha B lopinavir and inhalation alpha interferon and ebastine A Arm (unspecified) medicine Chinese + interferon atomised E Arm lopinavir/ritonavir D Arm (Novaferon) alpha interferon a2 B interferon atomised and darunavir/ritonavir A Arm interferon : peginterferon : r C Arm r D Arm : : : : : : : : : : r B Arm Arm Arm : : : 0YsNtrcutn China recruiting Not Yes China recruiting Not UK Unspecified 20 Recruiting 120 China Yes Recruiting 2000 Yes (Ascletis 100 China Recruiting Yes 50 13 Pharm) Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ICTPR ChiCTR2000029542 (ICTPR) ChiCTR2000029935 (ICTPR) ChiCTR2000029837 (ICTPR) ChiCTR2000029975 Antimalarial (ICTPR) ChiCTR2000029939 Antimalarial Antimalarial (ICTPR) Antimalarial ChiCTR2000029988 (ICTPR) Antimalarial ChiCTR2000030031 Antimalarial (ClinicalTrials.gov) NCT04304053 (ClinicalTrials.gov) NCT04252274 (ICTPR) ChiCTR2000029496 (ICTPR) ChiCTR2000029539 (ICTPR) ChiCTR2000030218 treatment standard B Arm chloroquine A Arm chloroquine A Arm chloroquine A Arm chloroquine A Arm treatment standard B Arm chloroquine A Arm treatment standard B Arm chloroquine A Arm chloroquine A Arm isolation B Arm darunavir/cobicistat A Arm treatment B cobicistat and darunavir A Arm lopinavir/ritonavir and Novaferon C Arm lopinavir/ritonavir halation in- atomisation Novaferon A Arm treatment standard B Arm lopinavir/ritonavir A Arm B injection Xiyanping and lopinavir/ritonavir A Arm standard : ritonavir : : : : : : : : : : : : : : : : : : : r B Arm Arm Arm : 0 oRcutn China China China Recruiting Recruiting China recruiting Not recruiting Not Unspecified China No Yes Recruiting No 20 100 China China 120 Yes 10 Recruiting Recruiting Spain Unspecified 100 Recruiting Yes China Recruiting 80 Yes 120 China Yes 3040 Recruiting China 30 Recruiting Yes China Yes 90 Recruiting Unspecified 328 80 14 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. (ICTPR) ChiCTR2000029803 (ICTPR) ChiCTR2000029559 (ClinicalTrials.gov) NCT04315896 (ClinicalTrials.gov) NCT04316377 (ICTPR) ChiCTR2000029899 (ICTPR ChiCTR2000029740 (ICTPR) ChiCTR2000029868 (ICTPR ChiCTR2000030054 (ClinicalTrials.gov) NCT04261517 (ICTPR) ChiCTR2000029898 (ICTPR) ChiCTR2000030718 hg dose) (high chloroquine B dose) (low ychloroquine A Arm hydroxychloroquine B Arm ychloroquine A Arm B Arm ychloroquine A Arm treatment standard B Arm ychloroquine A Arm chloroquine B Arm ychloroquine A Arm treatment standard B Arm ychloroquine A Arm treatment standard B Arm ychloroquine A Arm treatment standard B Arm ychloroquine A Arm care of standard B Arm ychloroquine A Arm chloroquine B Arm ychloroquine A Arm treatment standard B Arm chloroquine A Arm hydroxy- : : placebo : : : : : : : : : hydrox- : hydrox- : hydrox- : hydrox- : hydrox- : hydrox- : hydrox- : hydrox- : hydrox- : hydrox- : : Arm 2 e o eriigChina recruiting Not China Mexico Yes recruiting Recruiting Not Norway Unspecified recruiting 320 Not China Yes 300 Recruiting China Yes 500 Recruiting Yes China 202 Recruiting Yes 100 China recruiting Not China Yes 78 Recruiting China Yes 200 Recruiting China Yes 100 Recruiting Yes 30 Yes 100 80 15 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. .ilhYsYsN oYsYsYes No Yes No No Yes No Yes Yes Yes Yes Yes No Yes No No No No No Yes No Yes No Yes Yes Yes Yes manuscript. the of No content the complete to supports financial References any has Yes Supervision authors Yes the of None article final of approval and Funding Editing Yes Citation Yes writing draft Yes Original M.Billah Resources S.Karmakar Yes Curation Yes S.Das Data M.S.Rahman Conceptualization F.B.Mina Authors contributions interest. Author of conflicts no declare preclinical authors between drugs, The gap successful of interest translational production competing the rapid outbreak. of reduce the SARS-CoV-2 Declaration in will / problem 2019-nCoV approach major buying emerging also a our panic the should is study, overnight, for which public this purchases discovered outcomes, recent irrational clinical In a and induced cautiously from results and account. keep research lessons study will into the preliminary We repurposable taken a as [55]. of of be results COVID-19 trials results administration battling of trial revealed approval the in clinical which off-label for successful spree, successful or be setting releasing ethical can COVID-19 require before trials) the thus, optimistic of in and, IV stage experimental concern phase preclinical are in ethical in drugs is vital Oseltamivir are trials The clinical III, others of phase many either phases in [10][37][43][47]. and different trials, are under specified trials, clinical etc. drugs the clinical planned potential Cobicistat the the Darunavir, of of carefully for of Ritonavir, evaluated in decoction Many Lopinavir, be Remdesivir, 2019-nCoV The drugs. also other the (eg: 2019-nCoV. should with from and integrated the stability, or suffering and of alone patients safety used outbreak and of efficacy current recovery their the and for treatment overcoming assessed be in should time listed pivotal drugs a is It Conclusion (ICTPR) ChiCTR2000029803 (ICTPR) ChiCTR2000030082 dose) (high umifenovir dose) (low umifenovir A Arm umifenovir + alpha-interferon B Arm umifenovir) + alpha-interferon (presumed treatment antiviral with combined tablets piperaquine droartemisinin/ A Arm r B Arm : : dihy- : : 2 e o eriigChina recruiting Not Yes China Suspended 320 Yes 40 16 Posted on Authorea 20 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158739631.11698779 — This a preprint and has not been peer reviewed. Data may be preliminary. 1]D lrq .(09.Aohrtnsoisi niia rgdsoey(atC:od n nw antivirals, “new” C- and and C):“old” (part C-Nucleosides discovery drug of antiviral Biochemistry in perspectives. stories and ten and Chemistry Another strategies, (2009). The E. 1 Clercq, De (1985). [19] D. G. Jr, Daves In Arylglycosides. & against U., pyrazofurin Products Hacksell, In Natural of [18] Organic antibiotics. efficacy of C-nucleoside Antiviral Chemistry The the (1982). (1983). in L. stoffe/Progress G. W. J. Pannier, Buchanan, [17] discovery & Coronaviruses—drug B., (2016). P. Y. viruses. Jahrling, K. RNA Yuen, G., selected & P. S., Canonico, D. Hui, [16] model. I., E. animal Azhar, options. small F., therapeutic a J. and Chan, in A., (favipiravir) Zumla, T-705 [15] with infection virus Ebola research Infec- advanced Virus of Fever treatment Hemorrhagic L of L., Treatment Oestereich, the pneumonia [14] for A Analogues (2020). D. Nucleoside H. New Chen, (2019). & tions. origin. E. 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