An Overview on Treatment Strategies by Allopathic and Alternative Forms of Medicines in Management of COVID -19.

 

Smitha Sammith Shetty1, Vignesh Kamath2, Shibani Shetty3,

Swapna Bettanapalya Venkatesh4,

1Associate Professor, Department of Oral Pathology, Faculty of Dentistry, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal-576104, Karnataka.

2Senior Lecturer, Department of Prosthodontics, Manipal College of Dental Sciences, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka.

3Reader, Department of Oral Pathology, M.R Ambedkar Dental College and Hospital

Bangalore- 560005, Karnataka.

4Senior Lecturer, Department of Prosthodontics and Crown and Bridge, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka.

*Corresponding Author E-mail: swapna.bv@manipal.edu

 

ABSTRACT:

Coronavirus disease 2019 (COVID-19) is a new evolving infectious disease characterized as atypical pneumonia caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2). It was first seen in Wuhan, China, and later spread across the globe led to a worldwide pandemic affecting millions of people. The usual manifestations of COVID-19 include cough, sore throat, fever, dyspnoea, and fatigue with exposure recently. Most of COVID-19 patients may have mild or moderate disease, whereas severe to life-threatening disease course is seen in 5–10% of the patients. Several clinical trials are presently trying to find the most effective drug or combination of the drugs for this disease.  This article aims to discuss the treatment strategies in different forms of medicine that are being used for COVID-19 patients and review the literature available.

 

KEYWORDS: COVID -19, Treatment Strategy, Allopathy, Ayurveda, Homeopathy.

 

 


INTRODUCTION:

The new severe acute respiratory syndrome coronavirus (SARS-CoV), positive-sense RNA virus, non-segmented, an enveloped,  also known as 2019-nCoV, has affected a population of more than 34 million individuals and caused over 780,000 deaths globally since its first outbreak1,2.

 

A predominant characteristic of Coronavirus disease 2019 (COVID-19) is that it affects the respiratory tract, leading to severe pneumonia. Along with this, the patient faces an array of symptoms like moderate to high fever, cough resulting in acute dyspnea, and various other complications associated with acute respiratory distress syndrome3. The mutation rate of Coronavirus (CoV) is higher than that of other RNA viruses and it has a large genome4. Although, COVID-19 affects population of all ages, its prevalence is mostly seen affecting the elderly population, especially those with an immunocompromised state or in others suffering from one of the other debilitating diseases like heart conditions, uncontrolled diabetes, asthma and other breathing problems, obesity, liver and kidney diseases. They are often at high risk of unfavourable outcomes, which may require hospitalization3.

 

Despite a sharp climb in cases associated with its community spread, the therapeutic options for coronavirus are quite meager and uncertain1. To date, no scientific solution or a definitive treatment plan has been sought for this viral disease. Therefore, it has become imperative for several health care systems, scientists, and researchers to explore various strategies and find an effective therapeutic regimen to curb the spread of the virus5.

 

Since time immemorial, traditional medicines are proven to possess eminent and undeniable therapeutic advantage5. The strategy of using existing drugs to resolve the current ongoing situation is highly appreciated1.The adverse effects accompanied by the use of modern medicines have amplified the use of herbal drugs manifold6. In case of a medical emergency, however the allopathic system remains as the first choice6. The present article reviews the study of Ayurveda, Allopathy, and Homeopathy to develop a common strategy to combat the global pandemic caused by the coronavirus.

 

Structure of SARSCoV2 and Pathophysiology:

It is essential to understand the viral structure, replication cycle and genome in order to discuss the therapeutic agents currently used. Coronaviruses are positive-stranded RNA viruses, which contain a nucleocapsid and envelope7. The COVID19 causing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of the structural protein which includes the envelope (E), spike (S), membrane (M), and nucleocapsid (N) 8. The precursor spike protein (S) has been reported to bind to host surface protein via ACE2 (Angiotensin Converting Enzyme-2), dipeptidyl peptidase-4 (DPP4), and or glucose-regulating protein 78 (GRP78) receptors in the target cell with greater affinity8, 9.  Also, the level of affinity is much higher than the threshold required for virus infection9. The surface spike glycoprotein consists of two subunits, S1 and S2. The S1 facilitates the virus attachment to the host cell receptor, while the S2 coordinates the fusion of two cell membranes. This fusion activates the proteases, leading to cleavage of the cell membrane and translocation of the virus into the host cell10. Targeting the spike structural protein in coronavirus helps in preventing its binding to the target cell.

 

The  RNA of the virus  hijacks the machinery of the host cell to initiate the  replication of the viral genome and synthesis of polypeptides chain to form the replication-transcription complex (RCT) which is  needed to synthesize the sub-genomic RNAs and  structural proteins (envelope and nucleocapsid). The viral envelope plays a vital role in the viral assembly, release, and promoting pathogenesis of the virus7,11.

 

However, in already infected individuals, chymotrypsin-like protease (3CLpro) or also called main proteases (Mpro) play an important role in the replication and maturation of the coronavirus12. These proteins are the potential therapeutic targets for the development of antiviral drug against coronavirus.

 

Allopathic Pharmacological Intervention for Treating  COVID -19:

The literature search to date shows that COVID-19 patients manifest various symptoms, ranging from no symptoms to severe conditions like acute respiratory distress syndrome (ARDS)13. Favorable results are not obtained until date even after numerous medications are being tried. Unfortunately, to date, no drug has demonstrated efficacy for COVID-19 patients. Some of the treatment modalities currently in use are

 

Antivirals:

The use of anti-viral drugs such as lopinavir–ritonavir and ribavirin were advised based on previous experiences with SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV).

 

Lopinavir–ritonavir:

Ritonavir and lopinavir were initially used as antiretroviral drugs to treat HIV patients including adults, children above 2 years of age, and adolescents. They act by inhibiting the protease enzyme, which helps the virus in cleavage of long polypeptides chains for new viruses assembly14. The available data regarding their use in COVID-19 patients is limited  despite of   several ongoing trials. Chu et al 15 stated that viral load reduced and adverse clinical reactions with the use of lopinavir–ritonavir in patients with SARS when their virological and clinical assessment was done.  Chan et al16 in his study assessed the use of lopinavir–ritonavir in patients with severe acute respiratory symptoms, showed better clinical outcomes.

 

Remdesivir:

Remdesivir was first used for the treatment of Ebola. It acts by inhibiting the RNA-dependent polymerase and has demonstrated favorable anti-viral therapeutic effects when tested for efficiency in the treatment of SARS-CoV-2 infections17. Grein et al reported the use of  remdesivir  in 53 patients with severe COVID-19 and they showed clinical improvement (lowering of oxygen requirement)18.

 

Favipiravir:

It is a prodrug of purine nucleotide that is RNA polymerase inhibitor 19. Currently, the preclinical data are available in Japan 20. The drug has received approval in China for treating the novel Influenza virus.

 

Ribavirin:

A guanine analog that inhibits the viral RNA-dependent RNA polymerase21. It was used widely during the outbreak of SARS, but produced some adverse effects like hemolytic anemia. Ribavirin in combination lopinavir–ritonavir and interferon-β-1b showed a significantly shortened in the duration of viral              shedding22,23.

 

Chloroquine and Hydroxychloroquine:

They are widely used antimalarial drug, found to exhibit antiviral properties. The mechanism of action is by impairing the terminal glycosylation of ACE2 receptors, and decreases the acidity in endosomes compartments of infected cells, thus inactivating the virus. Few hospitals in China have successfully used chloroquine in reducing and treating the progression of COVID-19 in 100 plus patients. The ex-vivo studies conducted in the cell culture model have shown that the use of these drugs crippled the SARS-CoV-2 virus but a high dosage of the drug was required for its effectiveness causing severe toxicity24. However, WHO has temporarily suspended the use of hydroxy-chloroquine after analysing the safety concerns of antimalarial drugs25.

 

Interferon-α inhibits the replication of animal and human coronaviruses, whereas interferon-β acts against Middle East Respiratory Syndrome26,27,28,29. IFN-α is a broad-spectrum antiviral drug for the treatment of hepatitis. Many studies done previously have stated the results of the combination of interferon with ribavirin, lopinavir, or ritonavir. The drug has good efficiency against SARS-COV-2 in vitro23.

 

Convalescent plasma or passive immunotherapy was tried when no particular drug or vaccines were existing for infectious diseases. Different clinical trials are testing the systemic transfusion of convalescent plasma obtained from healthy donors who have completely recovered from SARS- CoV-2 on highly infected SARS-Cov-2 patients. This helped in reducing the cytokines in the acute phase of the disease and replenishes the patient’s own antibodies. Convalescent plasma containing neutralizing antibodies when administered, substantially decreased the viral load within few days post-transfusion and the patients clinical conditions improved significantly30,7.

 

Targeting COVID 19 (Sars-COV-2) Through Compounds Derived From Ayurvedic Medicinal Plants:

Multiple factors play important role in the transmission of COVID-19 such as host immunity, viral infectivity, host behaviour, and environmental factors. Of these only the host behaviour, host immunity can be managed and lies within the boundaries of human efforts31. In Ayurveda various herbs such as Ashwagandha, Avla, Ashwatha, Brahmi, Dhanyak, Rason, Guduchi, Haridra, Kutaki, Kantakari, Marich, Nimba, Pudina, Pippali, Shallaki, Sunthi, Tulsi, Twak, Vasa, Sunthi are recommended for viral ailments such as COVID-19. All these drugs have Antioxidants, anti-inflammatory, Immunomodulatory, antiviral and antimicrobial properties31.

 

However, few studies have reported with scientific evidence pertaining to the effectiveness and possible benefits of ayurvedic or plant-based drugs in the treatment of COVID19.

 

A few of the immunomodulators commonly used in Ayurveda such as Withania somnifera (Ashwagandha), Ocimum sanctum (Tulsi), and Tinospora cor- difolia (Giloy) has been studied in COVID19. The molecular docking exhibited a high binding affinity of 6 active phytochemicals in these compounds to SARS-CoV-2 Mpro32. Hence, these phytochemicals may be used to inhibit the action of SARS-CoV-2 Mpro, thereby preventing the translation of viral protein, which has a deleterious effect on vital organs in patients32.

 

The structural protein of SARS-CoV-2, the precursor spike protein (S) undergoes proteolytic cleavage by host cell transmembrane proteases such as transmembrane protease serine 2 (TMPRSS2), endosomal cathepsin L protease, or human airway trypsin-like protease (HAT), facilitating the fusion and translocation of the virus to the host cells25. The inhibitors of these proteases can inhibit the adherence of virus to host cells and hence the infectivity and progression of the infection33.

 

Withaferin-A (Wi-A) and Withanone (Wi-N), a bioactive phytochemical from Ashwagandha, has been reported to possess antiviral property34. Caffeicacid phenethyl ester (CAPE) from honey bee has also been proposed to have inhibitory effect against viruses35. Hence the ability of Withaferin-A (Wi-A) and and Withanone (Wi-N) and Caffeic acid phenethyl ester (CAPE) to dock and inhibit TMPRSS2 was studied. It was found that Wi-A and Wi-N both bind and interact with the catalytic site of TMPRSS2 but Wi-N showed higher interactions than Wi-A36.

 

The inhibitory role of Wi-N on TMPRSS2 expression was studied in MCF7 cells, where it induced the downregulation of TMPRSS2, inhibiting the fusion and infectivity of SARS-CoV-2 to the host cells36. The polyphenols like epigallocatechin gallate (EGCG), curcumin, and homoeriodictyol, isorhamnetin  are reported to simultaneously bind to 3 sites in the III and IV regions of the viral Spike protein and on its binding receptor sites of glucose-regulating protein 78 (GRP78) thereby preventing attachment, fusion, and translocation of the virus into the host cells8. Hence various plant- based products consisting of phytochemicals or polyphenols may have therapeutic potential against SARS-CoV-2. However, further bioassay studies may be required to confirm the inhibitory activity of these compounds against COVID19.

 

Homoeopathy and the Current Covid19 Challenge:

Specific antiviral drugs or vaccines against COVID-19 infection for therapy of humans is still not available to date37. Relevant to the current pandemic of the novel viral illness, is the story of Homoeopathy and the Flu pandemics in the past. As in other epidemics, Homoeopathy has proven its mettle not only as a prophylactic in flu-like illnesses but also as a line of treatment leading to faster recovery, decreased morbidity as well as mortality38. Owing to the unique approach and possibility to grant treatment early based on the semiology of the patient in any diseased condition, which helps in monitoring the progression of the disease, Homoeopathy has been a bane in many epidemics since antiquity38.

 

Homeopathy is based on the Hippocratic Similia Similibus Curentur therapeutic law. The physician usually relies on the totality of symptoms presented during the complete progression of the infection. An ultra -high diluted succussed solution product is generally prescribed that has already proven to heal similar conditions. This is the biggest benefit, especially in COVID-19 disease because the diagnosis is based on the person’s symptoms or the wholeness of symptoms and not on disease pathology and the treatment is by ultra-high diluted succussed solution. In conventional medicine, the physician waits until the causative agent is found whereas, in homeopathy the response of the organism is taken into consideration to the causative factor to initiate the treatment. Hence, with homeopathy, there can be immediate intervention, which can be helpful for the patient37.

 

A healthy harmonizing co-existence of modern medicine with other forms of medicine like Ayurveda, Homeopathy, Unani, and Siddha exists in India39.   The Health advisory  given by Ministry of AYUSH, Government of India, against COVID 19  included Homoeopathic medicine Ars alb 30c as a possible preventive medicine .  Arsenicum album 30 (Ars alb) was prescribed to more than 1500 patients with COVID-19 and continued for follow-up of 6-weeks. The subjects treated with Ars alb on follow –up showed that none developed COVID or any symptoms similar to COVID39. Ars alb has shown to affect HT29 cells and bring about decrease in NF-κB activity (reduced expression of reporter gene GFP in transfect HT29 cells) and TNF-α release in macrophages40. A trial conducted by Naiminath Homoeopathic Medical College, Hospital & Research Centre, Agra, India on 44 COVID-19 patients which showed that a homeopathic medicine Bryonia alba was more beneficial than Arsenicum album40.

 

In the Italian study on a group of 50 symptomatic Corona positive patients, they prescribed medications such as Bry alba (21 times), Ars alb (16 times), Phos flavus (9 times), Atr bell (6 times), Antim tart (6 times). The hospitalization rate of this group treated homeopathically for COVID 19 was zero and no undesirable events were observed during homeopathic treatments41.

 

In China, doctors formulated two sets of homeopathic symptom pictures of COVID-19 representing Bry alba and Gels. They gave Gels 30c as a preventive medicine to 4-5% of the population in one area and in another area out of 6,00,000 people 50% got Gels. In both the areas, no sick people were recorded. They also treated several mild or medium ill COVID-19 patients with Gels, Bry alba, Eup per in succession. They started to recover on the  first day and within 3 days they were healthy. The American Institute of Homeopathy database reveals Bry alba and Ars alb make up about 50% of the successful prescriptions41.

 

Historically, during the other epidemics of Spanish influenza, dengue fever, scarlet fever, Chikungunya fever, leptospirosis, and malaria, homeopathy was used in Europe as well as many other countries in the world. As there is scarcity of strong evidence-based regimens for anti-viral medications and conventional vaccines in the current COVID-19 pandemic, homeopathic medications has been used by 4–5% in the Hong Kong population and 45–50% in the Macau population as an adjunctive measure alongside conventional medicine in the management of influenza-like diseases42.

 

Bryonia alba, Calendula, Passiflora incarnata, and Zingiber officinale are other Homeopathic medicines which are in use for numerous other maladies.These medicines might prove to be potential inhibitors of ribosome-inactivating protein, proteases, and ACE-2, based on the properties of their source materials. Hence it may be of significance to investigate there role of these medications for the treatment of COVID-1943.

 

At present, the treatment of COVID-19 is symptomatic and managing emergencies using hospital facilities. The homeopathic medical system, whose foundation is based on symptomatic treatment, can play a vital role in tackling this global disaster. Several numbers of homeopathic medicines are there for patients with COVID-19 infection. Review and repertorization of the common symptoms of COVID-19 suggest Arsenic Album, Pulsatilla, Silicia, Nitrum Muriaticum, Phosphorus, Calcarea Carbonicum, Hyper Sulphur, Lachesis, Nux Vomica, Sulphur and many other medicines. Homeopathics pursue this using Synthesis Repertory- Treasure Edition, by Schroyens F, from Repertory Software Radar 10.0. By adding personalized character to these symptoms, a homeopathic physician might easily select the right individual remedy44.

 

It is the time to open the door to homeopathy, as morbidity and mortality could be dramatically lessened by the simple application of homeopathy in the current epidemic and can greatly speed up the recovery time without leaving patients weakened by the treatment41.  Homeopathy might contribute far more if its regional, local, national, and international bodies establish rapid-response teams and establish lines of communication.  These bodies should strive in Unison to improve interaction of homeopathy with mainstream medicine to work together45.

 

CONCLUSION:

COVID 19 was officially declared as “pandemic” by the World Health Organization (WHO) on March 11, 2020 46. As of November 28, 2020, more than 61 million people worldwide had been infected with severe acute respiratory syndrome coronavirus 2. Until date, not one treatment has been proven effective against COVID-19. This article has highlighted the status of the therapeutic agents in allopathy, Ayurveda, and homeopathy, which are being used in the battle against COVID-19. Although the therapeutic strategy against the disease is highly important, the key way to prevent virus spread is the development of the vaccine that is effective, safe and widely available.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

ABBREVIATIONS:

COVID-19: Coronavirus disease of 2019;

SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2;

SARS-CoV: Severe acute respiratory syndrome coronavirus;

CoV: Coronavirus;

ACE2: Angiotensin Converting Enzyme-2,

DPP4: dipeptidyl peptidase-4

RCT: Replication transcription complex;

ARDS: Acute respiratory distress syndrome;

MERS-CoV: Middle East Respiratory Syndrome Coronavirus;

TMPRSS2: Transmembrane protease

WHO: World Health Organization;

 

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Received on 30.12.2020            Modified on 27.05.2021

Accepted on 02.08.2021           © RJPT All right reserved

Research J. Pharm.and Tech 2022; 15(2):935-940.

DOI: 10.52711/0974-360X.2022.00156