Archives of Academic Emergency Medicine. 2020; 8(1): e29 REV I EW ART I C L E Potential Treatments for COVID-19; a Narrative Literature Review Ali Rismanbaf1∗ 1. Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Received: January 2020; Accepted: February 2020; Published online: 21 March 2020 Abstract: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recog- nized as a pandemic by the World Health Organization (WHO) on March 11t h . There is still no vaccine or defini- tive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed. Keywords: Coronavirus; Drug therapy; Clinical trial; Case reports; Review; COVID-19 Cite this article as: Rismanbaf A. Potential Treatments for COVID-19; a Narrative Literature Review. Arch Acad Emerg Mede. 2020; 8(1): e29. 1. Introduction SARS-CoV-2 (Severe Acute Respiratory Syndrome Coron- avirus 2) is a newly emerging human infectious coronavirus, originated in Wuhan, China, and has been spreading rapidly in China and other countries since December 2019 (1). The World Health Organization (WHO) also declared a global emergency on January 31s t due to increasing concerns over its fast spread, and on March 11t h the disease was recog- nized as a pandemic. Since the bases for pathogenesis of this virus and its proliferation is unclear, there is still no vaccine or definitive treatment against it. Thus, medications used against SARS-CoV-2 are mainly based on their effectiveness on earlier strains of coronavirus, SARS-CoV and MERS-CoV. Therefore, the immediate introduction of potential COVID- 19 treatments can be essential and salvaging. In this article, new potential COVID-19 therapies are briefly reviewed. 2. Methodology Articles were extracted, irrespective of time, using PubMed, Embase, and Google Scholar search engines, searching terms "COVID-19", "SARS-CoV-2", and "2019-nCOV" in titles, ab- stracts and keywords. Afterwards, clinical trials, clinical re- ports, case reports, and suggestions for potential medica- tions against COVID-19 were briefly reviewed. ∗Corresponding Author: Ali Rismanbaf; Isfahan University of Medical Sci- ences, Hezar Jerib Street, Isfahan, Iran. Email: alirismanbaf74@gmail.com, Tel: +989109747985 3. Results 3.1. Clinical reports Clinical reports on COVID-19 treatment mainly described empirical treatments and clinical experiences during its treatment. In 2020, Gao et al. studied the effect of chloro- quine and hydroxychloroquine in treatment of COVID-19 in over 100 patients and 10 hospitals in Wuhan, Jingzhou, Guangzhou, Beijing, Shanghai, Chongqing, and Ningbo. The results of this study showed that chloroquine phosphate is effective in preventing the exacerbations of pneumonia, de- creasing lung involvements in imaging findings, promoting a virus-negative conversion and shortening the disease course. In addition, there were no serious adverse effects observed at therapeutic doses (2). Also, according to Jian-ya et al., treatment of 51 COVID- 19 patients with traditional Chinese medicine, interferon, Lopinavir, Ritonavir and short-term (3 to 5 days) corticos- teroids was successful and resulted in recovery and discharge of 50 patients (3). Qin et al. also reported that administra- tion of moxifloxacin, lopinavir, and interferon to non-ICU patients and the addition of methylprednisolone to the above treatment for ICU patients resulted in 26 patients being dis- charged from intensive care unit (ICU) and 16 patients be- ing discharged from hospital (4). Also, Zhou et al. reported that short-term moderate-dose corticosteroid (160 mg/day) plus immunoglobulin (20 g/day) significantly reduced lung injury, normalized lymphocyte counts, body temperature, C- reactive protein levels, and oxygenation index in 10 COVID- 19 patients (5). On the other hand, while studying 416 This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem A. Rismanbaf 2 Table 1: Potential drugs for COVID-19 Study Method Medicine Mechanism of Action Wang et al. (2020) (12) In vitro study Chloroquine Remdesivir Reducing viral copy numbers in the cell supernatant and viral in- fection Zhang et al. (2020) (13) In vitro study Teicoplanin Preventing the entrance of SARS- CoV-2-Spike-pseudoviruses into the cytoplasm Xu et al. (2020) (14) Virtual screening Nelfinavir Binding to SARS-CoV-2 Mp r o Liu et al. (2020) (15) Virtual screening Colistin Valrubicin Icati- bant Bepotastine Epirubicin Epoprostenol Vapreotide Aprepi- tant Caspofungin perphenazine Binding to SARS-CoV-2 Mp r o Shang et al. (2020) (16) Virtual screening Rupintrivir Lopinavir Remdesivir Binding to SARS-CoV-2 Mp r o Jin et al. (2020) (17) Virtual screening Ebselen Binding to SARS-CoV-2 Mp r o Sekhar et al. (2020) (18) Virtual screening Beclabuvir Saquinavir Binding to SARS-CoV-2 Mp r o Contini et al. (2020) (19) Virtual screening (Angiotensin II human acetate) GHRP-2 Indinavir Cobicistat Caspofungin acetate Lopinavir Atazanavir Binding to SARS-CoV-2 Mp r o : Angiotensin II human acetate, GHRP-2, Indinavir, and Cobicistat Binding to SARS-CoV-2 3C-like proteinase (3CLp r o ): Angiotensin II human acetate, GHRP-2, In- dinavir, Caspofungin acetate, Lopinavir, and Atazanavir Wang et al. (2020) (20) Virtual screening Carfilzomib Eravacycline Valru- bicin Lopinavir Elbasvir Strepto- mycin Binding to SARS-CoV-2 protease Wang et al. (2020) (21) Virtual screening Thymopentin Carfilzomib Saquinavir Binding to SARS-CoV-2 3C-like proteinase (3CLp r o ) Chen et al. (2020) (22) virtual screening Ledipasvir velpatasvir Binding to SARS-CoV-2 3C-like proteinase (3CLp r o ) Beck et al. (2020) (23) Molecule Transformer-Drug Tar- get Interaction (MT-DTI) Atazanavir Efavirenz Ritonavir Dolutegravir Binding to SARS-CoV-2 3C-like proteinase (3CLp r o ) Elfiky et al. (2020) (24) Virtual screening Mycophenolic acid Grazoprevir Telaprevir Boceprevir Binding to SARS-CoV-2 papain- like protease (PLp r o ) Arya et al. (2020) (25) Virtual screening Formoterol Chloroquine Binding to SARS-CoV-2 papain- like protease (PLp r o ) Smith et al. (2020) (26) Virtual screening Eriodictyol Isoniazid pyruvate Ni- trofurantoin Cepharanthine Er- goloid Hypericin Binding potency to Viral S-protein at its host receptor region or to the S protein-human ACE2 interface Li et al. (2020) (27) Connectivity map (Cmap) Ikarugamycin molsidomine Effective on the genes co- expressed with ACE2 Richardson et al. (2020) (28) Using BenevolentAI Baricitinib Binding to AP2-associated protein kinase 1 (AAK1) Nowak et al. (2020) (29) Brief review Lithium Probably by reducing apoptosis and inhibition of glycogen syn- thase kinase 3 beta (GSK-3β) Sun et al. (2020) (30) Brief review Angiotensin converting enzyme inhibitors and Angiotensin1 re- ceptor inhibitors Rebalancing Renin-Angiotensin- Aldosterone System (RAAS) (might reduce the pulmonary inflammatory response and mortality) COVID-19 patients, Shang et al. reported that corticosteroid therapy and gamma globulin administration increased mor- tality and appeared to be useful only in patients with lower lymphocyte counts (6). According to the mentioned clinical reports, the administration of corticosteroids for COVID-19 patients is still questionable. 3.2. Case reports So far, there are three published case reports on the suc- cessful treatment of patients with COVID-19. In the first re- port Lim et al. described a 54-year-old man with COVID-19 who was treated with Lopinavir/Ritonavir from day 10 of ill- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2020; 8(1): e29 ness, 2 tablets (Lopinavir 200mg / Ritonavir 50mg) every 12 hours. Since first day of administration, β-coronavirus vi- ral load started to decrease, and little or no detectable coro- navirus titers have been observed since then (7). In an- other case report, Zhang et al. described a couple who were both 38 years old and were suffering from COVID-19. Their treatment included Methylprednisolone 40 mg daily intra- venous (IV ) injections for one and five days for the male and the female patient respectively, human gamma globu- lin 10g IV qd for five and seven successive days for the male and the female patient, respectively, and then the dose was changed to 5g for both of them, in addition to Moxifloxacin, Oseltamivir, Arbidol hydrochloride, and Tanreqing (Chinese patent medicine). After 11 days, the female patient and after 14 days the male patient recovered with regards to inflamma- tory factors and were discharged from the hospital (8). In the third case report, Chen et al. reported a 45-year-old woman with COVID-19 and stated that after treatment with Thalidomide (100 mg orally once a day) and Methylpred- nisolone (40 mg intravenously bid for 3 days then reduced to once a day for 5 days) the overall patient status was improved, oxygen index was increased, symptoms of nausea and vom- iting were alleviated, and cytokine levels were decreased (9). 3.3. Potential drugs Several articles have suggested medicines, potentially effec- tive for the treatment of COVID-19 (Table 1). Most of these suggestions are based on in vitro studies, virtual screenings and records of their effects on SARS and MERS. In addition to these medications, Tocilizumab has recently been suggested as a COVID-19 treatment. Studies have shown that IL-6 levels significantly correlated with the sever- ity of COVID-19, C-reactive protein (CRP), lactate dehydro- genase (LDH), and D-dimer levels and T cell counts, and it has been suggested that Tocilizumab, with its inhibitory ef- fect on IL-6, may be effective in treatment of COVID-19 (10, 11). However, no clinical study has demonstrated the effects of Tocilizumab on COVID-19 and further studies are indeed required. 4. Conclusion Apparently, in addition to the drugs currently prescribed to treat COVID-19, Arbidol hydrochloride, interferon, and Thalidomide plus Methylprednisolone can also be used due to their effects reported in clinical studies. However, more studies are needed to confirm the use of corticosteroids, as there are conflicting reports regarding their efficacy. Also, po- tential drugs listed in Table 1, such as Remdesivir, Atazanavir, Saquinavir, and Formoterol, and Tocilizumab can be intro- duced as treatments for COVID-19 if they prove to be effec- tive in animal and clinical studies. 5. Declarations 5.1. Funding Support None. 5.2. Conflict of Interest None. References 1. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. BioRxiv. 2020. 2. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Bio- Science Trends. 2020. 3. Jian-ya G. Clinical characteristics of 51 patients dis- charged from hospital with COVID-19 in Chongqing, China. medRxiv. 2020. 4. Qin X, Qiu S, Yuan Y, Zong Y, Tuo Z, Li J, et al. Clinical Characteristics and Treatment of Patients Infected with COVID-19 in Shishou, China. 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This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Methodology Results Conclusion Declarations References