Control of COVID-19 using Artesunate, an Antimalarial First Line Drug: A Review
Janmajoy Banerjee1, Ranabir Chanda2, Subhasis Samanta3, Dipanjan Karati4*
1Department of Pharmaceutical Technology, Gitanjali College of Pharmacy, Lohapur, West Bengal, India.
2 Principal, Sana College of Pharmacy, Kodad, Telangana, India, 508206.
3 Doctor, Binayak Multi-specialty Hospital, Sinthee, Kolkata, West Bengal, India, 700050.
4Department of Pharmaceutical Technology, Techno India University, Kolkata, West Bengal, India.
*Corresponding Author E-mail: karatibabai@gmail.com
ABSTRACT: Background: A novel human virus called coronavirus, SARS-CoV-2, or COVID-19, has become a pandemic disease. It was started last week of November 2019 in Wuhan, a city in China. It causes severe respiratory tract infections and other diseases. It is transmitted from human to human within incubation times between two to ten days. It is spread via droplets, contaminated hands, or surfaces. Recently research concluded the new SARS-Cov-2 coronavirus that causes the Covid-19 disease has a mutated gene that is found in the HIV virus. Plasmodium vivax and Plasmodium falciparum are two major types of the parasite which causes malaria in human. Main Body: More than 200 countries throughout the world have become suffered from malaria, and every year a large number of people die by the cause of malaria. We observed that there was no significant effect of coronavirus, SARS-CoV-2, or COVID-19 on malaria-affected countries. As per the recommendation given by World Health Organization, Artemisinin and its derivatives like Dihydroartemisinin, Artemether, Arteether, and Artesunate are used to kill parasites at an early phase of their development, quickly decreasing their numbers. Among all derivatives, Artesunate has the activity against HIV virus, and HIV virus has some structural similarity with coronavirus SARS-Cov-2 as both are RNA-based virus. There is a possibility for using Artesunate in malaria-infected countries; the coronavirus SARS-Cov-2 is unable to show a significant impact on malaria-affected countries. Conclusion: Zinc can increase the immunity against viral infections, especially on those viruses that cause infection in the respiratory tract. In our hypothesis, we suggest the use of Artesunate along with Zinc as a prophylaxis agent against coronavirus, COVID-19.
KEYWORDS: Coronavirus, SARS-Cov-2, COVID-19, Malaria, Artisunate, Zinc.
INTRODUCTION:
Coronaviruses belong in the genus of the Coronaviridae family. These are enveloped viruses with a large plus-strand RNA genome. The genomic RNA is 27–32 kb in size, capped, and polyadenylated. There are three serologically distinct groups of Coronavirus.
Within each group, viruses are characterized by their host range and genome sequence. Coronaviruses have been identified in mice, rats, chickens, turkeys, swine, dogs, cats, rabbits, horses, cattle, and humans and can cause a variety of severe diseases, including gastroenteritis and respiratory tract diseases. The family, Coronaviridae is comprised of two genera, Coronavirus, and Torovirus, which share similarities in morphology, genome organization, and genome expression.1-5
Three human coronaviruses were thoroughly investigated. HCoV-229E and HCoV-OC43 were identified in the mid-1960s and are known to cause the common cold. In 2003, another coronavirus SARS-CoV caused life-threatening pneumonia and is the most pathogenic human Coronavirus identified thus far. It has been proposed that SARS-CoV is the first coronavirus from the fourth group or that it is a group 2 outlier.6 Recently one human Coronavirus named COVID-19 has been identified. Its complete onset of action is still unknown, but this Coronavirus also causes life-threatening pneumonia along with other diseases. The SARS-CoV-2 is a β-coronavirus, which is enveloped non-segmented positive-sense RNA virus (subgenus arbovirus, Orthocoronavirinae subfamily). Human Beta-coronavirus, i.e., SARS-CoV-2, SARS-CoV, and MARS-CoV, have many similarities but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 contains a single standard (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs.7
According to the latest research, the novel SARS-CoV-2 Coronavirus possesses a mutated gene identical to the HIV virus. It can also assault human cells by attacking furin, an enzyme that acts as a protein activator in the human body. The researchers noted that the new coronavirus did not have the same HIV-like gene as other coronaviruses, such as the original SARS and the Bat-CoVRaTG13.8
History and epidemiology of COVID-19:
A recently recognized β-coronavirus caused pneumonia occurred in Wuhan, China, in December 2019. World Health Organization (WHO) officially revealed the disease as coronavirus disease 2019 or COVID-19. Coronavirus Study Group (CSG) of the International Committee proposed to name the new coronavirus SARS-CoV-2. Both official declarations were issued on 11 February 2020. On 7 January 2020, the Chinese scientists isolated a SARS-CoV-2 from a patient and came out to genome sequencing of the SARC-CoV-2. On 1 March 2020, a total of 79,968 cases of COVID-19 were confirmed in China, including 2873 deaths.7,9
The Chinese Center for Disease Control and Prevention (China CDC) organized a fast reaction team to assist Hubei province and Wuhan city health officials in conducting epidemiological and etiological studies in response to the epidemic. The WHO confirmed that the outbreak of the coronavirus, COVID-19 epidemic was related to the Huanan South China Seafood Marketplace, but no specific animal association was identified.10
Scientists were able to identify the first genome of coronavirus COVID-19 on January 10, 2020.11 Then the virus spread fast throughout China in less than a month. The early pattern of coronavirus, COVID-19, has shown a similar type syndrome-like severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) coronaviruses. Age, sex, and other health issues were all linked to susceptibility.12 The nature and types of coronavirus COVID-19 change rapidly. It rapidly changes its RNA configuration. At present, 11 types of coronavirus COVID-19 are active worldwide.
Symptoms of Coronavirus COVID-19:
Elevated body temperature, dry cough, and weariness are the most typical symptoms of coronavirus. Some patients may have aches and pains, nasal congestion, sore throat or diarrhea. These symptoms are usually mild and begin gradually. The majority of people, roughly 80%, recover from the ailment without requiring hospital treatment. One in every five patients infected with the coronavirus becomes extremely unwell and has trouble breathing. People over the age of 65 and those with underlying medical issues such as elevated blood pressure, cardiac and lung disease, diabetes, or malignancy, are more likely to acquire a severe illness. COVID-19 can be transmitted even by those who have only minor symptoms. Patients of all ages should seek medical help if they have a fever, or difficulty breathing.13-18
Prevention and Control:
WHO has recommended some methods and criteria which were used to prevent the spread of COVID-19 contamination? The first one is people should wash their hands recurrently with soap or alcohol-based hand rub. Everyone should keep a 1-meter gap between themselves and others who are coughing or sneezing. It is better to avoid touching the face with a hand. People should cover their mouth and nose when coughing or sneezing. People should stay at home if they feel unwell. Smokers should abstain from all forms of smoking as well as other lung-damaging activities. Everyone should keep a short physical gap between themselves and others.19-22
Main text:
We have selected some malaria-affected countries and malaria-free countries as tests and standard control for our experiment. We have selected the top 23 malaria-affected countries that are suffering from malaria (mainly caused by Plasmodium falciparum) as per WHO. We have selected these countries as our test sample11. In these countries, Artemisinin and its derivative Artesunate are used as a first-line medicine recommended by World Health Organization (WHO). It is also clear that Artemisinin and its derivative Artesunate are mainly used against Falciparum malaria.23-27
Table 1: List of major malaria affected countries (2016-17)
|
Sl No |
Country |
COVID-19 Infected |
Case/ 1M population |
Total Death by COVID-19 |
Death / 1M population |
|
1 |
Nigeria |
1095 |
5 |
32 |
0.2 |
|
2 |
The Democratic Republic of the Congo |
0 |
0 |
0 |
0 |
|
3 |
Tanzania |
284 |
7 |
10 |
5 |
|
4 |
Ethiopia |
117 |
1 |
3 |
0.03 |
|
5 |
Kenya |
336 |
6 |
14 |
0.3 |
|
6 |
India |
24530 |
18 |
780 |
0.6 |
|
7 |
Uganda |
76 |
2 |
0 |
0 |
|
8 |
Mozambique |
65 |
2 |
0 |
0 |
|
9 |
Ivory Coast |
1077 |
41 |
14 |
0.5 |
|
10 |
Ghana |
1279 |
41 |
10 |
0.3 |
|
11 |
Sudan |
174 |
4 |
16 |
0.4 |
|
12 |
Zambia |
84 |
5 |
3 |
0.2 |
|
13 |
Myanmar |
144 |
3 |
5 |
0.09 |
|
14 |
Cameroon |
1430 |
43 |
54 |
2 |
|
15 |
Madagascar |
122 |
4 |
0 |
0 |
|
16 |
Mali |
325 |
21 |
16 |
1 |
|
17 |
Burkina Faso |
629 |
30 |
41 |
2 |
|
18 |
Malawi |
33 |
2 |
3 |
0.2 |
|
19 |
Senegal |
545 |
33 |
7 |
0.4 |
|
20 |
Guinea |
954 |
73 |
6 |
0.5 |
|
21 |
Chad |
40 |
2 |
0 |
0 |
|
22 |
Burundi |
11 |
0.9 |
1 |
0.08 |
|
23 |
Niger |
681 |
28 |
24 |
1 |
Table 2: List of malaria free countries (2018) declared by WHO
|
Sl. No. |
Country |
% Infected of total world malaria cases |
COVID-19 Infected |
Case/ 1M population |
Total Death by COVID-19 |
Death / 1M population |
|
1 |
Argentina |
0 |
3607 |
80 |
176 |
4 |
|
2 |
Algeria |
0 |
3127 |
71 |
415 |
9 |
|
3 |
China |
0 |
82816 |
4632 |
58 |
3 |
|
4 |
Iran |
0 |
88194 |
1050 |
5574 |
66 |
|
5 |
Malaysia |
0 |
5691 |
176 |
96 |
3 |
|
6 |
Timor-Leste |
0 |
24 |
18 |
0 |
0 |
|
7 |
El Salvador |
0 |
261 |
40 |
8 |
1 |
|
8 |
Uzbekistan |
0 |
1804 |
54 |
8 |
0.2 |
This Artesunate has the anti-viral property, and it has activity against the HIV virus.28 We also have selected eight malaria-free countries certified by WHO as our control sample. As these countries are completely free from malaria, any kind of antimalarial drugs are not used here.29 Table 1 contains the name of the top 23 malaria-affected countries declared by WHO. Except in India, COVID-19 infected cases are very few in all countries. India has been suffering little high malaria-infected patients (24530) because of its high population. Except in India, total death caused by COVID-19 is also very low. In India, it is 780. Total COVID-19 infected cause per 1 million population and the total number of deaths per 1 million population are also very less. Even in India, these values are only 780 and 0.6, respectively. Table 2 contains the name of 8 completely malaria-free countries certified by WHO. We have considered table 2 as our controlled sample. The total number of COVID-19 infected causes, number of COVID-19 infected patients present per 1 million population, the total number of deaths caused by COVID-19, and the total number of deaths caused by COVID-19 per 1 million population are very high. Only Timor-Leste does not suffer any death case caused by COVID-19. The total number of COVID-19 infected patients in El Salvador and Uzbekistan is also low because of the low population. All data were collected on 18th April 2020 from world meter.30
DISCUSSION:
We observed that Artesunate is one of the first-line antimalarial drugs used to treat malaria patients. It also has anti-viral activity, especially against the HIV virus. Recently research has confirmed that the coronavirus COVID-19 has a similar mutated gene structure with the HIV virus. Both have identical RNA genomes. So, it may be considered to use Artesunate against coronavirus, COVID-19.
Artesunate is administered intravenously as 2.4mg per kg body weight as a loading dose followed by 1.2mg per kg body weight at 12 and 24 hours, then 1.2mg per kg body weight daily for six days.31
In IV administration, there is a problem that Artesunate hydrolysis to dihydroartemisinin (DHA), and no research still has confirmed that DHA has anti-viral activity, especially against the HIV virus. It has a shorter biological half-life (t ½). Half-life of IV dose of Artesunate is only 2.19 minutes and clearance 3.01 lit/kg/hr.
In the case of oral administration, if the patient takes Artesunate 200 mg once daily for five days, after administration in one-day biological half-life is obtained 43 minutes, and after five days of consequent administration, it is increased to 50 minutes.32
The standard oral dose of Artesunate against F. malaria is 100-200 mg initially. Then it may be continued as 100 mg daily for a further 2-4 days. Artesunate may be used as doses up to 16 mg/ kg body weight per day.33
In our observation, Artesunate may be used along with Zinc as combination therapy against coronavirus, COVID-19 because it has been confirmed that Zinc can improve the viral infection on upper respiratory tract like coronavirus, COVID-19.35-36
Zinc is an essential trace element that is used for development growth and the maintenance of body function. It acts on all organs and cells. Zinc deficiency is common mainly in developing countries, but it is not common in developed countries. Zinc increases viral immunity. Zinc deficiency leads the infectious disease caused by HIV or hepatitis C virus. It also increases the immunity against other anti-viral infections, especially against infectious viruses caused the infections in the respiratory tract. In case of respiratory tract infection, Zinc supplement is used as 10 mg per day for 8 to 14 days.
CONCLUSION:
Our work focuses on the new area of the treatment of patients caused by coronavirus, COVID-19. We suggested to use of Artesunate along with Zinc as a supporting element for the treatment of coronavirus; Artesunate is a well-known and widely used first-line drug used to treat malaria caused by Plasmodium falciparum, which is quite frequent in malaria-affected nations, particularly in Africa. We have observed that there is less coronavirus activity in malaria burden countries, especially those are affected by Plasmodium falciparum. Zinc is an essential element, and it is used to increase the immunology against virus infections, especially those that infect the respiratory tract. So, a combination therapy, i.e., Artesunate and Zinc, will be better to fight against coronavirus, COVID-19. We have suggested using combination of Artesunate and Zinc as prophylaxis treatment against coronavirus, COVID-19.
LIST OF ABBREVIATION:
China CDC: Chinese Center for Disease Control and Prevention; CSG: Coronavirus Study Group; DHA: dihydroartemisinin; WHO: World Health Organization; SARS: Syndrome-like severe acute respiratory syndrome; MERS: Middle East respiratory syndrome.
COMPETING INTEREST:
The authors declare that they have no competing interests
AUTHORS’ CONTRIBUTIONS:
RC and SS contributed to the conception and design of the review. JB, RC, and DK contributed to the completion of the search strategy and extraction of the relevant data. All authors were involved in the development of the manuscript drafted by JB. All of the authors have contributed equally to this paper.
All authors read and approved the final manuscript.
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Received on 28.04.2022 Modified on 24.08.2022
Accepted on 29.11.2022 ©Asian Pharma Press All Right Reserved
Asian J. Pharm. Tech. 2023; 13(2):130-134.
DOI: 10.52711/2231-5713.2023.00024