Reflections on the Special Experiment in General Medicine of the Non-Specific Antiviral Drug, and Authorized As Antitussive, Cloperastine

Original Article ISSN: 2581-771X

Reflections on the Special Experiment in General Medicine of the Non-Specific Antiviral Drug, and Authorized as Antitussive, Cloperastine. Talking Advantage of the Opportunity to Study its Effects on Coronavirus Disease 2019 (Covid-19) Jose Luis Turabian Specialist in Family and Community Medicine, Health Center Santa Maria de Benquerencia. Regional Health Service of Castilla la Mancha (SESCAM), Toledo, Spain.

ABSTRACT Cloperastine represents a special case on the list of drug repurposing potentially useful for treating COVID-19 in the early stages of the disease at the community or general practice level. Cloperastine is an antitussive drug marketed worldwide and especially by countries in North America, Europe, Japan, Brazil, Russia, India, China, South Africa, and Australia. The most common symptom of COVID-19 is cough. Therefore cloperastine already has the indication for its use in COVID-19. This supposes a comparative advantage over the rest of potentially useful reusable drugs for COVID-19, which may be indicated in comorbidities of the patient with COVID-19, but are not indicated for COVID-19 itself. Cloperastine is also a non-specific antiviral drug and has an action on the Sigma-1 receptor, which specifically resides in the endoplasmic reticulum membrane-associated with mitochondria. In addition, cloperastine is a type 1 sodium-dependent glucose cotransporter inhibitor, blocking glucose uptake in lung cells. A proposal is made to study the hypothesis of the potential effect of cloperastine in COVID-19, to assess the outcome of exposure to this drug (duration of symptoms, severity, hospitalization, viral load, etc.), in retrospective case-control studies and prospectively -and this possibility is a distinctive case of cloperastine compared to the rest of potentially useful drugs in the treatment of COVID-19-, through clinical trials, taking advantage of the special experiment of its authorized prescription from of the approved indication of cloperastine in the treatment of cough. Key words: COVID-19; SARS-CoV-2; Antiviral Drugs; Sigma-1 receptors; Biomedical Research; COVID-19 drug treatment; General Practice.

Address for Correspondence Author Dr. Jose Luis Turabian; Specialist in Family and Community Medicine, Health Center Santa Maria de Benquerencia. Regional Health Service of Castilla la Mancha (SESCAM), Toledo, Spain. E‑mail: [email protected] Crossref Doi: https://doi.org/10.36437/irmhs.2020.3.5.A

Introduction The severe acute respiratory syndrome proportions in March 2020.1,2 To date, coronavirus 2 (SARS-CoV-2) causing of COVID-19 has caused more than 34 million coronavirus disease 2019 (COVID-19), which cases and 1 million deaths worldwide.3 emerged in the human population at the end Therapeutic options and vaccines for COVID- of 2019, had already reached pandemic 19 are desperately needed to respond to

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Dr. Jose Luis Turabian; Reflections on the Special Experiment in General Medicine www.irmhs.com their ongoing. Finding effective treatments Therefore, it is clear that tools -drugs- are and vaccines will transform the impact of the needed to keep people alive, improve COVID-19 pandemic on lives and economies symptoms and reduce the duration and around the world. However, regarding severity of the disease. It is in this context vaccines, there can be a long way to go to find where it would be very useful to find an an effective vaccine. Among other antiviral drug that acts early, so that uncertainties, the effect of mutations on transmission can be reduced and contribute protein expression and the antigenicity to the control of outbreaks.7 required to elicit an antibody response (or to interact with passive antibodies) is unclear. Drugs that can be used as an early treatment For a decade, attempts to develop vaccines at the general medicine (GM) level are of against Severe Acute Respiratory Syndrome particular interest. Early treatment, if and Middle East Respiratory Syndrome have successful, would allow us to avoid the been unsuccessful. Furthermore, COVID-19 serious complications seen in COVID-19. The disproportionately affects older age groups, two promising categories of drugs targeting where immune senescence leads to poorer- COVID-19 viral infection and quality immune responses. Additionally, immunopathology are classic antivirals and infections with other coronaviruses and immunomodulators. While treatment for challenges with experimental vaccines have COVID-19 outside of the hospital setting is resulted only in short-term protective currently limited to supportive therapy, immunity.4 more than 1,000 clinical trials are underway looking at a variety of drug treatments.7,8 The On the other hand, the most useful public drugs -remdesivir and dexamethasone- of health approaches for slow transmission are which the first useful results are known to social and behavioral in nature.5 Control refer to hospitalized and seriously ill measures, based on isolation, contact tracing patients.8-10 and quarantine, can lessen and delay the burden of the ongoing epidemic, but these But, none of these interventions is applicable measures are associated with profound at the onset of the disease or at the social and economic disturbances; community level in GM. This line of furthermore, these interventions may be investigation has been overlooked. It should inadequate to control local outbreaks, even be borne in mind that all severe and critical when perfect isolation is assumed. The effect COVID-19 patients were previously mild or of infectivity before the onset of symptoms, moderate COVID-19 patients or uninfected combined with the presence of asymptomatic people. In addition to the benefits of early infected patients further complicates the use treatment, the preferable or ideal option of contact tracing. In short, useful drugs are would be to do it with an existing drug (drug needed. Therefore, research aimed at the repurposing): this method would be the identification of new drugs and drug re- fastest and most cost-effective clinical way to formulations suitable for therapeutic and mitigate the impact of COVID-19. That means prophylactic use (drug repurposing) for reducing hospitalizations, which can reduce different drugs with antiviral action through mortality, but it can also mean reducing viral different mechanisms, remains fully load, and that can have a profound impact on justified.6 transmission within communities.7

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Consequently, existing drugs are being In this scenario, this article aims to reflect on sought that could play a role in mitigating this case or special experiment of the COVID-19 or slowing its transmission. Drug potentially useful drug in COVID-19, repurposing is "a kind of fruit within the cloperastine, as drug repurposing, and as reach of clinical doctors." In this way, early treatment at the level of GM, thus outcomes data could be obtained quickly to taking advantages of the natural experiments help prioritize the drugs that could be tested that exist in its prescription authorized as in larger confirmatory studies.7,11-13 To date, antitussive in COVID-19. there is no specific medicine recommended to prevent or treat the new coronavirus, at Methods least at the level of GM, however, those For the literature review, a pragmatic infected with the virus should receive approach was used that was based on a non- appropriate care to relieve and treat systematic or opportunistic search for symptoms.14 information, considering the bibliographic references of selected articles, reviews of More than seventy drugs are being studied books related to the topic and searches on for their possible application in the COVID-19 Internet based on published studies on pandemic. Of these, some are drugs that are COVID-19 treatment. The comments in this already being used for various indications, article should be considered as a personal and others are experimental point of view, based on the author's pharmaceuticals. 26 of the 29 genes of the experience and the review cited above. SARS-CoV-2 have been studied in detail. At least 332 proteins in human cells become Discussion targeted by the coronavirus.15 Some viral Effective therapies are urgently needed for proteins target a single human cell protein; the SARS-CoV-2 pandemic. But, the other proteins in the virus appear to interact investigation of therapies against COVID-19 with dozens of cellular proteins. The accumulates failures, being the only two mechanism, barely deciphered, is of acceptable drugs, with mixed results, so far extraordinary complexity. Pharmacological remdesivir and dexamethasone. In general it research investigates drugs (already can be said that both antiviral drugs and marketed or substances with pharmaceutical immunomodulators might have their place in potential) that block the human proteins that the management of COVID-19. Unfortunately, the virus needs to first penetrate, and then no drugs have been approved yet to treat replicate, in the cell. Some specific infections with human coronaviruses. As it treatments are under investigation, and will will take years to develop new therapies for be tested through clinical trials. Among the SARS-CoV-2, the current focus is on the drugs that are already being used for various repurposing of drugs that have been indications and that could be repurposing approved or are in development for other drugs, is the antihistamine cloperastine, conditions.17 Thus, the ongoing COVID-19 which is a special case, as in addition to its pandemic has forced the clinical and possible antiviral effect, it is indicated as a scientific community to try drug repurposing non-opioid antitussive, and it can be used of existing antiviral or immunomodulators early and at the level of general medicine.16 agents as a quick option against SARS-CoV- 2.13

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The community level (out-of-hospital) Likewise, a number of approved and represents metaphorically "a Petri dish" common drugs have been reported for other where results of thousands of natural diseases or symptoms: 1) azithromycin and experiments are being produced against doxyclyne (for various infections), 2) alpha1 potentially useful drugs in COVID-19 that are antagonists (for arterial hypertension and waiting to be observed, and that behind some benign prostatic hypertrophy), 3) of them may be the discovery of a wonder tocilizumab (in the treatment of various drug. Meticulous community studies, at the types of arthritis, 4) statins (for general medicine level, should be done with dyslipidemia), 5) selective serotonin each of the natural experiments that are reuptake inhibitors, as fluoxetine, citalopram, taking place. In some of them, the "zone of sertraline, paroxetine, fluvoxamine, etc. (for antagonism" may appear, as it occurred in depression / anxiety), 6) antipsychotic, 7) serial experiments in the laboratory on the progesterone , 8) vitamin D or calcifediol search for antibiotics, and the tell-tale clear (25OHD), 9) vitamin C, 10) colchicine (for zone or "zone of antagonism may be visible rheumatological and cardiac conditions), 11) at an unexpected moment in a Petri dish, Angiotensin-converting enzyme (ACE) where one microbe battled against an enemy inhibitors and angiotensin II type 1 (AT1) for space or food." The richness of these receptor antagonists (for hypertension and experiments is that they are already heart failure), 12) ivermectine (as treatment underway, and their results can be quickly and control of several tropical diseases, 13) evaluated through retrospective studies, so with beta-blockers such as propranolol, that, like a gardener spotting a sturdy shoot, nebivolol, carvedilol, atenolol, etc. (for heart valuable results can be observed which problems and high blood pressure), 14) and would deserve to be verified with clinical antihistamines such as clemastine and trials.18 cloperastine (for cough of various causes).21

Using different methods, all known drugs A number of these drugs modulate proteins have been mapped against all the possible within the cell known as the Sigma-1 (Sig-1R) mechanisms in which SARS-CoV-2 operates and Sigma2 (Sig-2R) receptors, show to cause complications.7,15,19,20 And a number promise for clinical trials against COVID-19, of these have been reported to be promising including fluvoxamine, a commonly compounds for clinical trials against COVID- prescribed drug for depression, and which is 19: Some drugs can fight COVID-19, while a regulator of serotonin, but also activates others promote infectivity. Among them are the Sig-1R, progesterone, camostat, a transmembrane serine protease hydroxychloroquine; the antipsychotic drugs inhibitor licensed for use in Japan to treat haloperidol and cloperazine; siramesin, an pancreatitis and esophagitis, the antidepressant and anxiolytic drug; and the antiandrogenbicalutamide, zotatifine, and antihistamines clemastine and cloperastine. ternatine-4 / plitidepsin, niclosamide, That is, among this group of drugs, is favipiravir, leronlimab, interferon beta, cloperastine.15, 20, 21 interferon lambda, and other monoclonal antibodies, and a metabolite of the antiviral The Cloperastine Special Experiment: an drug remdesivir.7,15,20 Advantageous Opportunity Cloperastine represents a special case on the list of reusable drugs potentially useful for

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Dr. Jose Luis Turabian; Reflections on the Special Experiment in General Medicine www.irmhs.com treating COVID-19 in the early stages of the the control of arterial tone, fibrinolysis and disease. It is an antitussive drug available in vascular growth stand out. As if that were not many countries such as Japan, Hong Kong, enough, under physiological conditions the and some European countries, such as Spain; endothelium prevents inflammation and It was first introduced in 1972 in Japan and formation of blood clots. In COVID-19, then in Italy in 1981.22-28 Cloperastine is endothelial cells alter the integrity of the marketed worldwide and especially by vascular barrier. This would lead to tissue countries in North America, Europe, Japan, edema (accumulation of fluid in the lungs), Brazil, Russia, India, China, South Africa and inflammation of the endothelium Australia.29,30 In Spain, where it is available, (endothelitis), activation of the coagulation can be obtained without a prescription (it is pathways, and uncontrolled infiltration of not funded by the Public Health System), and inflammatory cells.39,40 Although it is still too it is prescribed and used frequently.31,32 And early to have a definitive answer, everything even clinical guidelines usually recommend it indicates that treatments that prevent for the treatment of dry cough.33-35 endothelial damage could be beneficial for COVID-19 patients. Here, Sig-1R, that is located in the endoplasmic reticulum, plays a On the other hand, coughing is the most modulator role.41 common symptom of COVID-19 (84%).36,37

And therefore cloperastine already has the Action of Cloperastine as a Potential Drug indication for its use in COVID-19. This in COVID-19 supposes a comparative advantage over the Cloperastine or cloperastine, also known as rest of potentially useful repurposing drugs cloperastine hydrochloride and for COVID-19, which may be indicated in cloperastinephendizoate (or hibenzoate), is comorbidities of the patient with COVID-19, an antitussive and antihistamine. but are not fully indicated (authorized) for Cloperastine was first studied at the COVID-19 itself. University of Tokyo and was introduced in COVID-19 as an endothelial disease Japan in the 70s of the last century.42 It is a COVID-19 can be conceptualized as an derivative of diphenhydramine. Scientists endothelial disease with respect to its found that this substance had a more effective complications. This unifying hypothesis can effect than codeine, which has been used for help understand the complex years to treat coughs. pathophysiology of this current plague and A cluster of SARS-CoV-2 antivirals with can also help inform our therapeutic characteristics of lysosomotropic agents, approaches to combat the consequences of meaning that they are lipophilic weak bases SARS-CoV-2 infection.38 Recent studies capable of penetrating into cells, has been suggest that pulmonary complications are the identified. These agents include cloperastine, result of a disturbance of the blood vessels. which are likely to inhibit SARS-CoV-2 The interior of the blood vessels is lined by a replication by non-specific (off-target) effects, single layer of endothelial cells. Research meaning that they probably do not act on carried out in recent decades has revealed its their "official" pharmacological targets, but role in a multitude of functions, among which rather interfere with viral replication through

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Dr. Jose Luis Turabian; Reflections on the Special Experiment in General Medicine www.irmhs.com non-specific effects on acidophilic organelles could be acting in the release of Ca ++ and in including autophagosomes, endosomes, and the inhibition of voltage-gated K + channels. lysosomes. In conclusion, in a tentative Sig-1R plays a role in modulating cathepsin B classification of SARS-CoV-2 antivirals into levels in macrophages derived from HIV-1 specific (on-target) versus non-specific (off- infected monocytes exposed to cocaine in target) agents based on their physicochemical vitro and in vivo (46). Nonopioid Sig-1R, as a characteristics, cloperastine would be among cellular factor, mediates the early steps of the non-specific (off-target) antivirals.43 viral RNA replication. In general, the initial steps of HCV infection have been reported to Cloperastine has an action on Sig-1R, which be regulated by Sig-1R.47 specifically resides in the endoplasmic reticulum membrane associated with The Sig-1R is unique endoplasmic reticulum mitochondria (an interface between protein that mediates signaling of a variety of endoplasmic reticulum and mitochondria). In drugs, and it is suggested that there is a Sig- addition to being able to translocate to the 1R-dependent modulation of cytokines.48 plasma membrane to interact with ion Receptor binding is one of the main channels and other receptors, Sig-1R also determinants of tissue tropism for occurs in the nuclear envelope, where it coronaviruses and appears to be an recruits chromatin remodeling factors to important mediator of the pathophysiology of affect gene transcription. Sig-1Rs have also COVID-19. The SARS-CoV-2 spike protein been reported to interact with other plays the most important roles in viral membranous or soluble proteins at other loci, binding, fusion, and entry, and serves as a including the cytosol.44 target for the development of antibodies, entry inhibitors, and vaccines. It has been The Sig-1R is a transmembrane protein hypothesized about the possible participation expressed in many different tissue types. It is of a wide range of receptors in the entry of particularly concentrated in certain regions of SARS-CoV-2 cells. A foregoing line of evidence the central nervous system. It has been supports the hermeneutical notion that the implicated in several phenomena, including SARS-CoV-2 might enter the cell via cardiovascular function, schizophrenia, angiotensin-converting enzyme-2 receptors. clinical depression, addiction to Presumably, Sig-1R and Sig-2R might play a methamphetamine or cocaine, cancer, role in the infectivity of SARS-CoV-2. Previous amnesia, pain, depression, Alzheimer's research has suggested that pharmacological disease, stroke, neuroprotection of the retina, manipulation of both Sig-1R and Sig-2R and HIV infection. Sig-1R is thought to be a activity might provide antiviral activity, pluripotent modulator with multiple resulting particularly for RNA viruses including functional manifestations in living hepatitis C virus (HCV) and human systems.44,45 immunodeficiency viruses (HIV). These Much is known about the binding affinity of findings indicate that sigma receptors may hundreds of synthetic compounds to the Sig- also be involved in the cellular transmission 1R, although its mechanisms of action with of SARS-CoV-2, which has a genomic respect to other biochemical agents are not structure similar to that of HCV and HIV.49 well established. It is thought that the Sig-1R

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Furthermore, cloperastine has another effect; considering that cloperastine is a drug that is it is actually a type 1 sodium-dependent in many medicine cabinets in the homes of glucose cotransporter (SGLT1) inhibitor. It ordinary people, and that it could improve blocks glucose uptake in lung cells (27, 50). COVID-19, more research is needed on it. Selective analogs of the natural glycoside floridzin are marketed drugs that reduce Regular use of cloperastine: the natural hyperglycemia in diabetes by inhibiting the experiment in Spain (and in other active sodium-glucose cotransporter SGLT2 countries like Japan or Italy) in the kidneys. Additionally, intestinal SGLT1 Cloperastine is a cough suppressant and is now recognized as a target for glycemic antihistamine; it’s already the right indication control. Among the new SGLT1 inhibitors in COVID-19. This fact makes it more beyond the glycoside chemical space is interesting in relation to its possible efficacy cloperastine.50 against COVID-19. Furthermore, it's readily available in many countries, even though it's Epithelial glucose transport is performed by mainly sold in Japan and European countries, Na + -glucose transporters SGLT1 and SGLT2. especially Spain. On the other hand, Spain or In the intestine, glucose uptake in the diet is Italy was some of the countries where the mediated for the most part by SGLT1, and first wave of COVID-19 was most intense, humans with mutations in the SGLT1 gene from March to May 2020. Spain, likewise, is show glucose / galactosemalabsorption. In being the country with the highest infection the kidney, both SGLT1 and SGLT2 rates in Europe from July to September 2020, transporters are expressed, and recent in the second wave (at the time of writing this studies have identified that SGLT2 mediates article), and it is one of the countries with the up to 97% of glucose reabsorption.51 The most deaths from COVID-19 by the number of study of primary human lung cells that were inhabitants (Peru, Belgium, the United infected in the laboratory with SARS-CoV-2 Kingdom, and Spain, are the countries with showed how the cells began to accumulate the most deaths with coronavirus by the large amounts of lipid droplets. After number of inhabitants: Peru leads the ranking infection, lung proteins decrease the ability of with 87 deaths per 100,000 inhabitants, while lung cells to burn carbohydrates and fatty Spain registers 61; In addition, Spain had the acids. Lung cells are not designed to retain fat, second-highest mortality rate in the worst of which could explain some of the severe the pandemic).52 damage to the lungs of COVID-19 patients.

The virus is dependent on glucose absorption, The coincidence of these facts means an cholesterol production, and fatty acid opportunity for the clinical-epidemiological oxidation.27 study, by offering a special natural Outcomes of cloperastine on COVID-19 experiment, where cloperastine is being used Researchers have reported a 20% or 30% as an antitussive, and probably frequently in reduction in the virus, in the laboratory, what the dry cough of an upper respiratory vial in is only a modest reduction (27), and all types of patients, including COVID -19. cloperastine has only been tested against the This situation would allow, with some ease, virus in laboratory experiments (15, 20). But, the performance of retrospective case-control

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Dr. Jose Luis Turabian; Reflections on the Special Experiment in General Medicine www.irmhs.com studies53 (which may be common to all drugs Biomed; 91(1):157-60. repurposing with a potential effect on COVID- https://www.mattioli1885journals.co 19), but also prospective studies, using the m/index.php/actabiomedica/article/ drug in its approved indication, as an view/9397 antitussive in COVID-19, which is a special 2. Guan W-J, Ni Z-Y, Hu Y, et al. (2020) case of this drug. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med; Randomized clinical trials remain the best 382(18):1708-20. available method for understanding the https://pubmed.ncbi.nlm.nih.gov/321 causal relationship between an intervention 09013/ and subsequent evolution at the population 3. Coronavirus COVID-19 Global Cases level for most diseases, but in the absence of by the Center for Systems Science and data from randomized trials, there is an Engineering (CSSE) at Johns Hopkins. obligation to rely on observational studies.54 The Center for Systems Science and However, with cloperastine, it would be Engineering (CSSE) at JHU. possible to carry out clinical trials without https://www.arcgis.com/apps/opsda violating any ethical norm, and with adequate shboard/index.html#/bda7594740fd sample sizes.55 and in the application of these 40299423467b48e9ecf6 treatments in the clinical practice of GM as 4. Coronavirus COVID-19 Global Cases well as early in the evolution of COVID-19. by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins. Conclusion The Center for Systems Science and The proposal is made to study the hypothesis Engineering (CSSE) at JHU. of the potential effect of cloperastine in https://www.arcgis.com/apps/opsda COVID-19, a drug used as an antitussive and shboard/index.html#/bda7594740fd that has potential actions as a nonspecific 40299423467b48e9ecf6 antiviral, taking advantage of the natural 5. Ramirez-Valles J, Breton E, Chae DH, experiment of its high prescription in some Haardörfer R, Kuhns LM (2020) The places, to assess both retrospectively the COVID-19 Pandemic: Everything Old effect of exposure to that drug and the results Is New Again in Public Health of the disease (duration of symptoms, Education. Health EducBehav; 47(4): severity, hospitalization, viral load, etc.), as 501-3. prospectively - and this possibility is a https://doi.org/10.1177/109019812 distinctive case of cloperastine compared to 0935067 the other drugs potentially useful in the 6. Torneri A, Libin P, Vanderlocht J, et al. treatment of COVID-19-, based on clinical (2020) A prospect on the use of trials, from the approved indication of antiviral drugs to control local cloperastine in the treatment of cough. outbreaks of COVID-19. BMC Med; 18:191. References https://doi.org/10.1186/s12916- 1. Cucinotta D, Vanelli M (2020) WHO 020-01636-4 Declares COVID-19 a Pandemic. Acta

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7. Stokowski L (2020) Could These Old April 30. Drugs Help Fight COVID and Save https://www.nytimes.com/2020/04/ Lives? Medscape; Sep 08. 30/health/coronavirus-antiviral- https://www.medscape.com/viewarti drugs.html cle/937021?nlid=137264_4663&src= 13. Clementi N, Ferrarese R, Criscuolo E, WNL_mdplsnews_200911_mscpedit_f et al. (2020) Interferon-β-1a med&uac=327178AR&spon=34&impI Inhibition of Severe Acute Respiratory D=2559953&faf=1#vp_1 Syndrome–Coronavirus 2 In Vitro 8. Scudder L (2020) Drug Treatment for When Administered After Virus COVID-19: A Quick Summary for Infection. J Infect Dis; 222(5): 722-5. PCPs. Medscape; Jul 15. https://doi.org/10.1093/infdis/jiaa3 https://www.medscape.com/viewarti 50 cle/933966_1 14. WHO (2020) Coronavirus disease 9. NIH (2020) NIH clinical trial shows (COVID-19) advice for the public: Remdesivir accelerates recovery from Mythbusters. advanced COVID-19. NIH. News https://www.who.int/emergencies/d Releases; April 29. iseases/novel-coronavirus- https://www.nih.gov/news- 2019/advice-for-public/myth-busters events/news-releases/nih-clinical- 15. Gordon DE, Jang GM, Bouhaddou M, et trial-shows-remdesivir-accelerates- al. (2020) A SARS-CoV-2 protein recovery-advanced-covid-19 interaction map reveals targets for 10. Spinner CD, Gottlieb RL, Criner GJ, et drug repurposing. Nature; 583: 459- al. (2020) Effect of Remdesivirvs 68. https://doi.org/10.1038/s41586- Standard Care on Clinical Status at 11 020-2286-9 Days in Patients With Moderate 16. Font E (2003) [Drugs for the COVID-19: A Randomized Clinical treatment of cough]. [Article in Trial. JAMA. Spanish]. Offarm; 22(11): 70-8. https://jamanetwork.com/journals/j https://www.elsevier.es/es-revista- ama/fullarticle/2769871 offarm-4-articulo-farmacos-el- 11. Nazeam J, Mohammed EZ, Raafat M, et tratamiento-tos-13055921 al (2020) Based on Principles and 17. Delang L, Neyts J (2020) Medical Insights of COVID-19 Epidemiology, treatment options for COVID-19. Eur Genome Sequencing, and Heart J Acute Cardiovasc Care; 9(3), Pathogenesis: Retrospective Analysis 209-14. of Sinigrin and ProlixinRX https://doi.org/10.1177/204887262 (Fluphenazine) Provides Off-Label 0922790 Drug Candidates. SLAS DISCOVERY. 18. Pringle P (2012) Experiment Eleven. https://doi.org/10.1177/247255522 Dark secrets behind discovery of a 0950236 wonder drug. New York: Walker & 12. Zimmer C (2020) Old Drugs May Find Company. a New Purpose: Fighting the 19. Brooks M (2020) Six Potential Coronavirus. The New York Times; Treatments for COVID-19 Identified.

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How to cite this Article: Jose Luis Turabian; Reflections on the Special Experiment in General Medicine of the Non-Specific Antiviral Drug, and Authorized as Antitussive, Cloperastine. Talking Advantage of the Opportunity to Study its Effects on Coronavirus Disease 2019 (Covid-19); Int. Res. Med. Health Sci., 2020; (3-5): 1-13; doi: https://doi.org/10.36437/irmhs.2020.3.5.A

Source of Support: Nil, Conflict of Interest: None declared. Received: 24-8-2020; Revision: 18-10-2020; Accepted: 22-10-2020

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