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Covid-19: An Account On Novel Coronavirus Disease

Yogita Ozarde 1*, Preeti P Mehta2, Manish S Wani 1, Jivika A Naik 1, Bhakti N Jadhav1 ,and Gayatri M. Karadkhedkar1

1 Department of Pharmaceutical Chemistry, Dr.Vishwanath Karad MIT World Peace University School of Pharmacy, Pune- 411038, India

2 Department of Pharmaceutical Chemistry, School of Pharmacy, Vishwakarma University, Pune-411048, India

ABSTRACT

COVID-19 is a highly infectious viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The world is facing threatening health crisis with the rapid spread of COVID-19 since December 2019 as it emerged in seafood market of Wuhan, South China. The virus outbreak has been declared a public health emergency of international concern by the World Health Organization (WHO). The virus mainly affects the upper (sinuses, nose, and throat) or lower (windpipe and lungs) respiratory tract. Fever, cough, sore throat, dyspnoea, weariness, and malaise are some of the symptoms of the infection. No any clinically proven antiviral medication or vaccine is available to treat covid 19 infection; hhowever, only a few broad-spectrum antiviral medicines have been tested in clinical trials and have shown to be effective. Oxygen therapy and improving immune system are amongst the other measures. Identification and isolation of confirmed infected people and suspected people is necessary to avoid the spread of infection to other patients and health-care personnel. The attempt has been made in this review article to compile the data regarding Covid 19 with respect to its pathophysiology, current clinical characteristics, diagnosis, prevention, treatment. Information about Government initiatives, role of pharmacist and alternative herbal medicines for Covid 19 have also been added.

The data was gathered from several research reports, articles and WHO guidelines. It was compiled to prepare a comprehensive review that would help the reader to understand the basics about the disease and create awareness among society.

Keywords

COVID-19, Coronavirus, SARS-CoV, Pandemic.

Introduction

Coronavirus disease is a communicable disease caused by a new metabolic process virus known as

“severe acute metabolic process syndrome coronavirus 2” (SARS-CoV-2) that was first identified in Wuhan, China in December 2019 [1-5].The sickness was known as Novel coronavirus sickness 2019 [6,7]. COVID-19 is a respiratory illness that results in delicate to moderate symptoms in affected patients. World Health Organization might recover with none medical intervention. People that have compromised immunity because of underlying medical conditions like cancer, diabetes, human immunodeficiency virus (HIV), etc.and people over the age of sixty are more likely to experience serious, even fatal symptoms. Coronavirus, like many other different viruses, is also prone to changes in its genetic structure because of the process known as mutation. In this Review, we summarize pathophysiology, transmission, treatment and methods of prevention of COVID-19. This review also highlights herbal alternatives recommended for treatment of coronavirus infections.

Classification and taxonomy of coronaviruses

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Coronaviruses are classified based on the crown like appearance of the envelope glycoproteins, and on characteristic features of chemistry and replication. Coronaviruses are categorized into 39 species,27subgenera, 5 genera, and 2 subfamilies of the Coronaviridae family, taxonomic group Cornidovirineae, order Nidovirales, and realm Riboviria [8,9]. Mutations units are influenced by totally different external environment factors; therefore, these numbers would possibly go on increasing. The family classification and taxonomy are developed by the Coronaviridae Study Group (CSG), a working group of the International Committee on Taxonomy of Viruses (ICTV) [10]. There are six human coronavirus species with one species sub-divided into two different strains, making seven strains of human coronaviruses in total.In the classification of nidoviruses, species are biological organisms characterized by genetics-based method while virus species are usually recognized as artificial or man- made constructs. To completely comprehend the difference between a nidoviral species and the viruses grouped therein, it may be instructive to look at their relationship in the context of the full taxonomy structure of several coronaviruses.

Etiopathophysiology

An individual gets the infection when the spherical lipoidal envelope of virus holding the long strand of genetic material inside gets entry. This outer envelope has coiled spring-like parts at the core and spike glycoprotein (S protein) on surface (Fig.1).

Figure 1. Structure of SARS-CoV-2

The S protein is essential for virus attachment and subsequent virus entry into the host, by transforming into two separate polypeptides S1 and S2, mediated by cellular protease enzymes, furin and transmembrane serine protease 2 (TMPRSS2) [11].

The Membrane Protein has ion channel forming activity which allows access to host endoplasmic reticulum (ER); wherein binding happens by a receptor binding domain (RBD) present in S1. The viral

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in nucleocapsid phosphoprotein long strand.

In Beta Corona Viruses, one of four genera of coronaviruses, a Hemagglutinin-esterase dimer protein (HE), does the binding of sialic acids on surface glycoproteins. S protein-mediated cell entry is enhanced for faster virus propagation through mucosal linings. In infected cell ER, the viral RNA is read to make proteins assisting virus particle reproduction. The host cell is directed to make 30 assorted parts predominantly the Golgi complex and then Vesicle with replicated Virus which spreads through exocytosis for further spreading and replication (Fig.2) [12-15].

Figure 2. Pathogenesis of COVID-19

Blood pressure regulating cells containing external protein called angiotensin converting enzyme2 (ACE2) act as receptors to 2019-nCoV infection [16]. The gastrointestinal mucosa, the upper and lower respiratory tract, myocardium tissues show ACE2 expression. Accordingly, epithelial cells of the intestine, lung alveoli, blood vessels, kidneys become target for binding of human pathogenic corona virus. Drug regimen of Type-1 or Type-2 diabetes includes ACE inhibitors and angiotensin II type-I receptor blockers (ARBs). Thus, ACE2 expression is increased. Hypertension also involves an upregulation of ACE2. Thiazolidinediones and ibuprofen cause increase in ACE2 upon administration.

Active smokers also show increased expression of ACE 2 and higher risk of infection. Consequently, COVID-19 infection is facilitated by an increase in ACE2. So, the chances of developing severe and fatal COVID-19 symptoms are increased by ACE2- stimulating drugs while treating diabetes and hypertension. However, ACE2 reduces inflammation and has been preferred as a potential treatment for inflammatory lung diseases, hypertension, diabetes and even cancer. So, the hypothesis of increased COVID risk could lead to a contradiction.

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Asian populations, with diseases like cerebral stroke, diabetes mellitus and hypertension, show genetic predisposition due to ACE2 polymorphisms thus posing another factor in the etiology of SARS-CoV-2 infection. Recently in January 2020, cases of acute respiratory syndrome after travel to Wuhan were studied in China to understand the COVID-19 pathogenesis. Alveolar injury, cellular fibromyxoid exudates, and pneumocyte desquamation were all observed in patients with acute respiratory distress syndrome. In early-phase acute respiratory distress syndrome (ARDS), the features include lymphocytes seen in Interstitial mononuclear inflammatory infiltrates, formation of hyaline membrane and pulmonary oedema. Multinucleated syncytial cells with atypical enlarged pneumocytes with large nuclei, amphophilic granular cytoplasm, and prominent nucleoli in the intra alveolar spaces are among the other characteristics. COVID-19 pathology shows great similarity to features seen in SARS and Middle Eastern respiratory syndrome (MERS) corona virus infection. Corona virus infection also leads to lymphopenia as a symptom, thereby increasing the severity of disease. In conclusion, hyper-activation of T cells is seen, exhibited by increased Th17 and high cytotoxicity of CD8 T cells [17-19].

Transmission

COVID-19 virus is transmitted between people through respiratory droplets in the air and contact routes.

Transmission of respiratory infections occurs through droplets of different sizes. When the droplets are more than 5µ in diameter, they are referred to as respiratory droplets and when they are less than 5 µ in diameter, they are referred to as droplet nuclei. Droplet transmission occurs when a person comes into close contact (within 1 m) with someone who is coughing or sneezing and is thus exposed to potentially infectious droplets in the air from his or her mucous membranes (mouth and nose) or conjunctiva (eyes).

Transmission can also occur through fomites in the immediate environment of the infected person.

Hence, COVID-19 virus transmission can occur by direct contact with infected people and indirect contact with surfaces in the immediate environment or with objects used by the infected person (Fig.3).

Airborne transmission differs from droplet transmission in that it refers to the presence of microbes inside droplet nuclei, which can remain in the air for a long time and can be transferred to others over distances greater than one meter [20-24]. COVID-19 infection may also lead to intestinal infection and be present in feces. But, only one study has cultured the COVID-19 virus from a single stool specimen to date [25]. No reports of COVID-19 virus transmission from faecal-oral route have been found till date.

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Figure 3. Mode of transmission of COVID-19

Symptoms [26]

Wide range of symptoms, ranging from mild symptoms to severe illness are reported in people with COVID-19. Symptoms may appear 2-14 days after exposure to the virus. People with these symptoms may have COVID-19:

Fever or chills

Cough

Shortness of breath or difficulty breathing

Fatigue

Muscle or body aches

Headache

New loss of taste or smell

Sore throat

Congestion or runny nose

Nausea or vomiting

Diarrhoea

Prevention

The best way to deal with this global pandemic is by taking preventive measures [27] such as:

Wash your hands regularly with soap and water for at least 20 seconds or use an alcohol-based hand sanitizer.

Maintain at least one-meter distance between yourself and someone who is coughing or sneezing.

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Avoid touching your eyes, nose and mouth without washing your hands first.

Cover your mouth and nose when coughing or sneezing.

Stay at home if you're not feeling well.

Avoid smoking and other lung-damaging practices.

Practice physical distance by preventing unnecessary travel.

People with mild symptoms who are otherwise safe should self-isolate and contact their doctor or a COVID-19 data line for testing and referral advice. People who have a fever, a cough, or a respiratory problem should contact their doctor and seek medical assistance.

Youngsters have an additional active innate immunologic response, healthier metabolic process tracts as compared to adults as there’s less exposure to pollution and smoke, and also adults have few underlying disorders [28]. An additional vigorous immunologic response in adults may justify a prejudicious immunologic response that’s related to acute metabolic process distress syndrome.

Based upon on the market data until now the high risk for the COVID-19 unwellness includes [29-31]:

People with chronic respiratory diseases Respiratory illness patients

People with serious heart conditions Cancer patients

Immunocompromised folks People with polygenic disease People with nephrosis or disease Pregnant ladies

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Figure 4. Tips to prevent coronavirus transmission

Treatment

Currently, no antiviral medication is confirmed as a treatment for COVID-19. Treatment is directed at providing symptomatic relief and includes Analgesic drugs like ibuprofen or acetaminophen. For relief from constant coughing, cough syrups may be prescribed. Increased fluid intake allows for faster recovery and rest is advised to help cope with the disease symptoms. One of the foremost development necessary to subsume the worldwide pandemic is an antibody therapy and despite substantial progress in producing coronavirus antibodies for medicinal use, no antibody has yet been successfully commercialized. In vitro replication of several coronaviruses was found to be inhibited by antimalarial drugs like chloroquine and hydroxychloroquine. A recent research supports the hypothesis that antimalarial drugs can boost clinical results in SARS-CoV-2 patients [32]. The molecular mechanisms by which chloroquine achieves these effects are still being studied. The treatment of cases of aggravated Covid-19 ill patients whereby variety of countries like China or the US and France all have confirmed positive results for the use of this therapeutic protocol.

An antiviral drug, Remdesivir, is currently the only drug that is approved by the FDA for the treatment of hospitalized COVID patients who require supplemental oxygen [33,34]. A corticosteroid, Dexamethasone, has been found to effective in hospitalized patients who require mechanical ventilation [35,36]. Combination therapy including dexamethasone and tocilizumab, an anti-interleukin-6 receptor

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monoclonal antibody, was found to improve survival of patients who require invasive mechanical ventilation due to COVID-19[37].

A distinctive feature of severe respiratory disorder in patients infected with COVID-19 is the accumulation of pus and mucous secretion within the alveoli, bronchioles and bronchi that prevents air flow within the tract and disrupts gas exchange within the lungs, which leads to hypoxic injury to brain cells and consequently death of patients. [38]. In such conditions it is generally accepted that only one method known as extracorporeal membrane oxygenation (ECMO) can save the life of patients with severe acute respiratory distress. But this procedure is found to be very complex and expensive, hence it is not available to everyone. However, an easy, cheap and publicly available alternative method of extrapulmonary oxygenation was proposed recently. It involves administration of a solution of hydrogen peroxide carbonated with oxygen by injection in the right place or in the form of aerosol. This aerosol is able to quickly dissolve thick pus and thick mucus in the respiratory tract in obstructive bronchitis.

But the use of hydrogen peroxide and its method of application have not passed clinical trials yet and are not included in the standard treatment of pneumonia and obstructive bronchitis in patients infected with COVID-19[39-41].

In the dire conditions presented by the coronavirus pandemic, it is vital to not only take utmost care of one’s health but also manage stress and anxiety involved. This can be done by regular intake of healthy meals, well managed sleep schedule, physical activity like yoga or regular exercise will help to boost one’s immunity. Meditation and relaxation exercises such as deep breathing and stretching are recommended to avoid stress. If one is detected positive for coronavirus disease, he/she must take plenty of rest to aid faster recovery, increase one’s fluid intake and seek immediate medical attention if the symptoms worsen. Supportive steps include aerosols, endotracheal intubation, bronchoscopy, open suctioning, nebulized care administration, manual ventilation prior to intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, non-invasive positive-pressure ventilation, tracheostomy, and cardiopulmonary resuscitation.

Recommended herbal alternatives

One of the mechanisms that plays a role in pathogenesis and leads in poor outcomes in COVID- 19 patients is impaired immune control. Herbal immunomodulators can help to prevent or even cure the disease in the early stages. Few herbs being investigated for the treatment of covid 19 and most of the natural plant phytoconstituents used as immunomodulators are discussed here.

Turmeric, Curcuma longa, belongs to the Zingiberaceae family and genus Curcuma is an herbal plant, most commonly used as kitchen spice, and natural colouring and flavouring agent in food.

It has been demonstrated that, turmeric works as an antiviral agent by preventing viral entry into cells, suppressing viral replication, and regulating cytokine levels.

Quinine alkaloids, which have been used to cure malaria for centuries, are produced by Cinchona trees (Chincona L., Raiatea) and have been reported to have valuable benefits in healing fever.

SARS-CoV-2 infection can be suppressed in vitro using hydroxychloroquine, a less toxic derivative of chloroquine [42].

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Repositioning or repurposing of the natural compounds like ursolic acid, hederagenin, oleanolic acid, sageone, apigenin, glabridin, found in apple peels, cucurbit vegetables, olive oil, mint family plants, red pepper, Glycyrrhiza respectively is required to evaluate their potential in treating COVID disease.

The molecular docking approach had been used to investigate the beneficial effects of a variety of phytochemicals found in Indian herbs such as Haldi, Giloy,Tulsi, Ginger, Black pepper, lemon, Clove, Cardamom, and Ashwagandha in the treatment of cough, cold, and flu. Docking scores revealed that these phytoconstituents possess significant anti-inflammatory property, and potential to inhibit various stages of SARS-CoV-2 infection and other target proteins [43].

Herbal remedies may thus have the ability to regulate the synthesis and release of proinflammatory cytokines, interfere with the virus's growth in host cells, and alter some RAA-related cellular pathways. However, there have been no particular preclinical and clinical research to investigate the effects of herbal immunoregulators [44].

Arogya Setu Important Outcomes:

The pandemic crisis has made the Union Government and also the state Govts invest in mobile apps development to support the population. Different State-level apps share the same device architecture and many of the same functionalities, such as self-testing, quarantine tracking, and touch tracing. The Government of India, Ministry of Electronics and Information Technology has actively promoted both the installation and use of the Aarogya Setu app, making it available in 11 Indian languages for convenience [45,46].

Figure 5. Arogya setu app

Role of Pharmacist

Pharmacists all over the world are playing a critical role in developing creative techniques to mitigate the pandemic's negative effects. Some of them are as follows:

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• To protect the environment, raise awareness of the latest NHS guidelines for community pharmacies about COVID-19.

• To reinforcee sensible approaches and hygiene measures such as regular hand washing and the use of hand sanitizers, through display of posters and data about virus containment.

• To support the immune system by encouraging balanced eating habits and provide food and nutrition advice.

• To encourage people to be more considerate of others, particularly the elderly and those with health issues.

• To provide symptomatic relief by prescribing OTC medicines.

• To rrecommend moisturizing creams to consumers, as repeated hand washing and the use of hand sanitizers can cause dryness and damage the skin's integrity.

• To make suitable arrangements for corona virus patients to order their drugs and have them shipped or picked up by family or friends.

• To determine who has been impacted, and to take a few minutes to provide social support and encourage patients to make them feel less alone and nervous [47-50].

Conclusion

COVID-19 is challenging all human beings. Covid-19 virus pandemic has posed a threat to China's economic, medical, and public health infrastructure, as well as that of other countries, particularly its neighbors. Tackling this epidemic is a long-term job which requires efforts of every individual, and international collaborations by scientists, authorities and the public. In addition, new outbreaks of zoonotic viruses and diseases are anticipated to occur. Hence in addition to controlling current outbreak, efforts should be undertaken to develop comprehensive strategies to prevent future zoonotic outbreaks.

Acknowledgements

The authors are thankful to the Dean and management of School of Pharmacy, Dr. Vishwanath Karad MIT World Peace University, Pune- 411038, India. for their encouragement and availing the internet and library facilities for this review.

Conflict of Interests

The authors report no declarations of conflict of interest regarding publication of this article.

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