Current Drugs with Potential for Treatment of COVID-19: A Literature Review

- Purpose: SARS-CoV-2 first emerged in China in December 2019 and rapidly spread worldwide. No vaccine or approved drug is available to eradicate the virus, however, some drugs that are indicated for other afflictions seems to be potentially beneficial to treat the infection albeit without unequivocal evidence. The aim of this article is to review the published background on the effectiveness of these drugs against COVID-19 Methods: A thorough literature search was conducted on recently published studies which have published between January 1 to March 25, 2020. PubMed, Google Scholar and Science Direct databases were searched Results: A total 22 articles were found eligible. 8 discuss about treatment outcomes from their applied drugs during treatment of COVID-19 patients, 4 report laboratory tests, one report animal trial and other 9 articles discuss recommendations and suggestions based on the treatment process and clinical outcomes of other diseases such as malaria, ebola, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The data and/or recommendations are categorized in 4 classes: (a) anti-viral and anti-inflammatory drugs, (b) anti-malaria drugs, (c) traditional Chinese drugs and (d) other treatments/drugs. Conclusion: All examined treatments, although potentiality effective against COVID-19, need either appropriate drug development or clinical trial to be suitable for clinical use. __________________________________________________________________________________________


INTRODUCTION
The world has experienced various dangerous outbreaks of various intensities such as ebola, cholera, Spanish flu, American seasonal flu.Now we are facing an arguably a more dangerous viral endemic with COVID-19.This severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as the 2019 novel Coronavirus (2019nCoV or COVID- 19), is a single-stranded RNA beta-coronavirus whose genome encodes are structural proteins, non-structural proteins and accessory proteins (1).It has globally already infected 413467 people and killed 18,433 people by 25 March, 2020 (2) and the casualties are growing exponentially.In the meantime, only 113453 patients have recovered which is 27.45% of total affected population (2).The characteristics of the infected population is already published (3,4).Various treatments have been suggested and applied to control COVIDE-19 based on previous experiences with other viral infections such as malaria, ebola and cholera (6).In addition, a systematic review of the effect of chloroquine on COVID-19 infection has appeared (5).However, these treatments have resulted in controversy as are not based on data generated from direct conventional clinical trials albeit, a list of ongoing registered clinical trials have been reported by Zhang et al (7).Herein, a thorough literature review on these treatments are presented.

Search and selection strategy
A literature search was conducted to cover the period January 1-March 25, 2020.PubMed, Google Scholar and Science Direct databases were selected as search strings.EndNote X 9.0 software was used to exclude duplicates from searched data."Treatment for COVID-19" AND "Vaccine, Anti-viral drugs, Antimalaria drugs, Traditional Chinese Medicine for COVID-19" such keywords were using in search string without considering any restriction of language to identify potential published studies.Moreover, missing studies were identified by checking the reference list of the selected articles.
The studies which describe about the current treatment process and drugs for COVID-19 infection were selected to conduct this study wherein some editorial and letter to editor were also included which mainly recommended some drugs based on the treatment process of previous epidemic viruses such as malaria, ebola, severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS).Meanwhile, studies which (a) duplicate publications (b) full articles not available (c) literature reviews and (d) do not provided sufficient information or support regarding their recommendation of their proposed drugs or treatment process were excluded.However, few articles which are still in press also selected for this analysis to meet the aim of this study.The steps taken to conduct the present search are presented in Figure 1.

Data extraction and analysis
To conduct this study the author, date, name and category of the drugs, effectiveness of the drugs, reason for effectiveness, the type of observation (hospital/ clinical trial/ animal trial/ laboratory) were recorded.For the case studies and laboratory tests, when the drugs applied, the size of the dose, sex and age of patients were noted.

RESULTS
A total of 1153 articles initially identified.After removing duplicates, checking title, abstract and full text 22 were found eligible based on the predetermined exclusion and inclusion criteria for this study.From this 22 articles, 8 were case reports which reported treatment of COVID-19 patients, 4 reported laboratory tests, one reported animal trial and others 9 reported recommendations and suggestions based on experience involving the use of drugs in other viral infection; i.e., malaria, ebola, severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS).These studies are summarized in Table 1.Based on the information and authors comments, the drugs are categorized  Form Google Scholar, n=355 From Science Direct, n=243 From Web of Science, n=202 After removing duplicates articles, n=52 Anti-viral and Anti-malarial

DISCUSSION and CONCLUSION
This literature review and analysis was conducted based on recently published studies on treatment of COVID-19 diseases.This review clearly demonstrates that the available data are not sufficient to suggest any treatment for eradication of COVID-19 to be used at the clinical level.All human studies lack comparative data so that it remains unclear whether the patient recovered because of the use of particular drug or the general clinical care received.Most in vitro studies, however, are suggestive of potential beneficial effects although the data are too preliminary to be used as rationale for clinical use.
The motivation for the use of antiviral drugs to treat COVID-19 infection, a viral disease, is obvious.However, the interest in the use of antimalarial drugs stems in the unexpected finding of beneficial effect of hydroxychloroquine in the treatment of HIV patients (29).Nevertheless, the beneficial effects of chloroquines in patients with COVID-19 needs to be tested through appropriately conducted clinical trials.However, a point that needs careful attention is the safety profile of these two antimalarial drugs.The toxicity of chloroquine is well-acknowledged, but it is often ignored that hydroxychloroquine is a relatively safe drug being used by a vast population of patients with early rheumatoid arthritis (30).Therefore, the focus of the studies may need to be on hydroxychloroquine instead of more toxic chloroquine.

LIMITATIONS
This literature review has few limitation.For inclusion, very few studies were available and most of them were from a single geographic location.For better understanding of the genetic and environmental effects, studies involving patients from other geographical regions are needed.Additionally, detailed information of patients, clinical and laboratory outcomes of recommended drugs were unavailable for most of the cases included in this review.

Figure 1 .
Figure 1.Summary of study selection design

Table 1 .
Summary of findings reported in selected articles