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Beschreibung

This handbook provides an introduction to COVID-19 and herbal medications that boost the human immune system against SARS-CoV-2. The topics are covered in 7 chapters starting with an introduction to the disease, followed by notes on nutraceuticals and common herbal medicines that have therapeutic potential by enhancing the patient’s immune response. Special topics such as COVID-19 risk factors and Indian traditional medicines are also included to supplement the contents. The editors have taken advantage of the vast body of knowledge accumulated since the start of the COVID-19 pandemic in 2019.
Chapters are written in simple language with structured headings to facilitate a quick understanding of the subject. References are provided for scholars interested in further readings. The book is a quick guide on immune boosting medicines for a broad audience that includes general medical practitioners, nurses, caregivers, and public healthcare workers involved in clinics working in local communities.

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Table of Contents
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
Usage Rules:
Disclaimer:
Limitation of Liability:
General:
PREFACE
List of Contributors
Origin of COVID-19
Abstract
1. INTRODUCTION
2. Historical Background, Origin and the Transmission of Coronavirus
3. Classification of Coronavirus
3.1. Differences and Similarities Between SARS, MERS, and the nCoV-2019
3.1.1. Similarities and Differences
4. Structure of Coronavirus and Role of their Proteins
4.1. Coronavirus Structure
4.2. Spike Protein and its Drawbacks into the Host Body
5. MECHANISM OF VIRAL ENTRY
6. Modes of Transmission
7. TREATMENTS OF COVID-19
7.1. Antiviral Agents
7.2. Natural Products
7.3. Vaccines
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
COVID-19: Sign, Symptoms and Transmission
Abstract
1. INTRODUCTION
2. Signs, Symptoms and Severity Status of Covid-19 Patients
3. Factors that Aggravate COVID-19 Condition
3.1. Age
3.2. Obesity
3.3. Smoking
3.4. Drinking
3.5. Immune System Condition
3.6. Human Selectivity and Reactivity
4. FACTORS THAT ENHANCE THE TRANSMISSION OF COVID-19
4.1. Misdiagnosis
4.2. Poverty
4.3. Perception and Illiteracy
4.4. Asymptomatic Patients
4.5. Climatic Influence
4.6. Low Vitamin D level
Conclusion
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
Acknowledgements
References
A Silver Lining for Covid 19: Nutraceuticals and Plant Secondary Metabolites
Abstract
1. INTRODUCTION
2. Immunity Booster Nutrients
2.1. Vitamin A
2.2. Vitamin B6
2.3. Vitamin B12
2.4. Vitamin C
2.5. Vitamin D
2.6. Vitamin E
2.7. Iron
2.8. Zinc
2.9. Selenium
2.10. Amino Acids
2.11. Arginine
2.12. Glutamine (GLN)
3. Nutraceuticals
3.1. Probiotics
3.2. Omega-3 fatty Acids
3.3. β-glucans
3.4. Secondary Plant Metabolites Against COVID-19 Virus
3.4.1. Alkaloids
3.4.2. Terpenoids
3.4.3. Polyphenols/flavonoids
4. Emerging Challenges and Potential Solutions
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Risk Factors of Covid-19 Enhancing Transmission and Aggravating Patient’s Condition
Abstract
1. INTRODUCTION
2. COVID-19 BIOLOGY (GENOME, GENE AND PROTEINS)
2.1. Virus Life Cycle
3. FACTORS OF DEMOGRAPHIC
3.1. Age and Gender
3.2. Ethnicity
4. FACTORS RELATED TO OCCUPATIONS
4.1. Smoking
5. COMPLICATION IN COVID-19
5.1. Acute Kidney Injury (AKI)
5.2. Coagulation Disorders
5.3. Thromboembolism
5.4. Anticoagulants
6. RISK FACTOR OF CANCER AND COVID-19
6.1. Inflammation and Immune-Senescence
6.2. Metabolic Syndrome
6.3. Immunosuppression, Interferon and Neutrophilia
6.4. Relationships Between Cancer and Covid-19 Susceptibility or Therapies
7. Anticancer Drugs Used to Increase the Vulnerability of COVID-19
8. PRO-COVID-19 EFFECTS ON CANCER THERAPY
8.1. Interferon Therapy
8.2. Immune Blockers
8.3. JAK– IL-6–STAT3 Blockade
8.4. Androgen-Deprivation Therapy
8.5. Other Small Molecules
8.6. ANTIVIRAL DRUGS THAT HAVE SHOWN ANTITUMOR EFFECT AGAINST COVID-19
9. RISK FACTORS OF CARDIOVASCULAR SYSTEM AND COVID-19
9.1. Cardiovascular Comorbidities Underlying
9.2. Cardiovascular Manifestations of Diverse
9.2.1. Myocarditis
9.2.2. Cardiovascular Diseases and Covid-19 Bidirectional Interaction
9.2.3. Acute Coronary Syndrome
9.2.4. Heart Failure
9.2.5. Cardiac Arrest
9.2.6. Coagulation and Thrombosis
9.2.7. Kawasaki Disease
9.2.8. Immunocompromised Patients
10. ACE2 Manifestations in Cardiovascular Diseases
10.1. ACE2 Downregulation for COVID 19
10.2. Therapeutic Target ACE2
10.3. COVID 19 Broad Tissue Tropism
10.4. Endothelial Cells for Viral Targeting
10.5. Drug–Disease Interactions
10.5.1. RAAS Inhibitors on COVID 19
10.5.2. Antiviral Drugs for Cardiovascular Effects
10.5.3. Hydroxychloroquine and Azithromycin
10.5.4. Remdesivir
10.5.5. Lopinavir–ritonavir
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Indian Expedition against Covid-19 through Traditional Drugs
Abstract
1. INTRODUCTION
1.1. Disease Etiology
1.2. Regulation of Spike Protein
1.3. Indian Traditional Drugs
2. Indian Herbal Formulations Used As Immunity Booster for Covid-19
2.1. Alium Sativum
2.2. Ocimum Sanctum
2.3. Cinnamomum Verum
2.4. Acacia Arabica
2.5. Azadirachta Indica
2.6. Citrus Limon
2.7. Zinger Oficinale
2.8. Curcuma Longa
2.9. Plant Metabolite Potential as Immunity Booster for Covid -19
2.9.1. Flavonoids
2.9.2. Polyphenols
2.9.3. Terpenoids
2.9.4. Dipeptides
3. Scope, Challenges and Potential Solution
3.1. Challenges
3.2. Potential Solution
4. Future Prospects
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Herbal Therapy for COVID-19
Abstract
1. INTRODUCTION
1.1. Herbal Therapy as a COVID-19 Treatment Option
2. COVID-19 Herbal Therapy/Herbs
2.1. Echinacea Purpurea
2.2. Curcumin
2.3. Cinchona SP.,
2.4. Withania Somnifera
2.5. Planax Quinquefolius (Ginseng)
2.6. Fenugreek
2.7. Herbal Extracts and Nutraceuticals [29]
2.7.1. Vitamins
2.7.2. Minerals in the Diet
Selenium
Zinc
Iron
N-acetyl-cysteine Amino Acid (NAC)
2.7.3. Probiotics
2.7.4. Omega-3 fatty Acids
2.8. Tinospora Cordifolia (Giloy, Guduchi)
2.9. Ocimum Sanctum, (Holy Basil, Tulsi)
2.10. Syzygium Aromaticum (Clove, Laung)
2.11. Sambucus Nigra (Elderberry)
2.12. Allium Sativum (Garlic, Lahsun)
2.13. Zingiber Officinalis (Ginger)
2.14. Traditional Indian Medicines
2.15. Rebooting of the Immune System
2.16. COVID-19 Herbal Therapy: The Role of Specific Phyto-constituents
2.16.1. Phenolic Compounds
2.16.2. Saponins
2.16.3. Alkaloids
2.16.4. Polysaccharides
2.16.5. Anthraquinones
3. Herbal Therapy's Future Prospects Against COVID-19 and Overcoming Challenges
Final Thoughts/Conclusion
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Herbal Immune-Booster for COVID-19
Abstract
1. Introduction
2. Outbreak of Coronavirus in the 21st Century
3. Traditional Medicine in Corona Pandemic
4. Plant Based-Immunity Booster for COVID-19
4.1. Terpenoids
4.2. Polyphenols and Flavonoids
4.3. Dipeptides for COVID-19
4.4. Polysaccharides for Immunity
4.5. Vitamin D Rich Foods
4.6. Vitamin C and E Rich Foods to Induce Immunity
4.6.1. Vitamin A
4.6.2. Minerals
4.7. Nutraceuticals Supplements and Probiotics for Immunity
5. Indian Spices Applicable as an Immune Booster
5.1. Herbal Formulations for COVID-19
6. Challenges, Potential Solutions, and Future Prospects
Conclusion
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Herbal Immunity Boosters Against COVID-19
Edited By
Sachin Kumar Jain
Oriental College of Pharmacy & Research
Oriental University
MP-452010
India
Ram Kumar Sahu
Department of Pharmaceutical Science
Sushruta School of Medical and Paramedical Sciences
Assam University (A Central University)
Silchar-788011, Assam
India
Priyanka Soni
B R Nahata College of Pharmacy
Mandsaur University,
Mandsaur Assam
India
&
Vishal Soni
B R Nahata College of Pharmacy
Mandsaur University,
Mandsaur Assam
India

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PREFACE

The book is an exclusive version of the instructive matter on Herbal Immunity Boosters for Covid-19. The herbal immunity booster is basically an emerging field that discusses potential preparations to diminish the severity of the infection caused by Covid-19. Currently, the effective treatment of COVID-19 is lacking. Hence it is imperative for individuals to use such type of food supplements which boost their immune systems. In this concern, the ideal technique is to fortify immunity naturally by using medicinal plants. Whereas, immunity booster deals with the remarkable protection mechanism against loads of bacteria, viruses, fungi, toxins and parasites when entering the body. Additionally, other signaling pathways are recognized that are responsible for the regulation of the pathogenesis of infections and non-infectious diseases due to lower immunity. It also deals with the exploration of functional and nutraceutical foods for preserving body homeostasis which is essential to maintain immunity. Therefore, plants or herbs having immunomodulating properties should be included in the diet, and we should explore novel therapeutic opportunities to improve immunity against diseases. This book contains immense knowledge about Herbal Immunity Boosters for Covid-19 with respect to the mode of action, modulation of signaling pathways, regulatory aspects, safety, food supplements and drug delivery for better function of the immune system. In addition, drug development issues, adaptation to clinical use, market prospects and industrial commercialization too come under the concept of Herbal Immunity Boosters for Covid-19. The book not only focuses on theoretical knowledge but also considers practical aspects. The book is very beneficial for students and researchers across the globe that are indulged in the reading and investigation of Herbal Immunity Boosters for Covid-19, thereby, spreading awareness all over the globe and promoting anticipated trends in the field of Herbal Immunity Boosters. The major objective of this initiative is to bring into light the entire fundamental concept. This book also includes different types of procedures and herbal medicines to increase and treatment and immunity of Covid-19.

Sachin Kumar Jain Oriental College of Pharmacy & Research Oriental University Ujjain Road Indore MP-452010 IndiaRam Kumar Sahu Department of Pharmaceutical Science Sushruta School of Medical and Paramedical Sciences Assam University (A Central University) Silchar-788011 Assam, IndiaPriyanka Soni B R Nahata College of Pharmacy Mandsaur University, Mandsaur Assam India &Vishal Soni

List of Contributors

Ankit JainIPS Academy College of Pharmacy, Rajendra Nagar AB Road, Indore MP, IndiaAseem SetiaDepartment of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab-142001, IndiaChayanika BordoloiNEF College of Pharmacy, Guwahati, Assam, IndiaDeepshikha VermaInstitute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Koni, Bilaspur-495009, Chhattisgarh, IndiaKm. Nandani JayaswalDepartment of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab-142001, IndiaLubhan SinghKSCP, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, IndiaNeetesh Kumar JainFaculty of Pharmacy, Oriental University Indore, MP, IndiaNitu SinghFaculty of Pharmacy, Oriental University Indore, MP, IndiaPriyanka PandeySwami Vivekanand College of Pharmacy, Indore, Madhya Pradesh, IndiaRam Kumar SahuDepartment of Pharmaceutical Science, Assam University (A Central University), Silchar, Assam – 788011, IndiaRaja ChakrabortyInstitute of Pharmacy, Assam Don Bosco University, Tepesia Garden, Sonapur, IndiaRakesh SagarDepartment of Pharmacy SGSITS, Indore MP, IndiaRavindra Kumar PandeyColumbia Institute of Pharmacy, Tekari, Raipur, Chhattisgarh, IndiaRetno WidyowatiDepartment of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, IndonesiaRupesh Kumar PandeyKSCP, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, IndiaSaikat SenFaculty of Pharmaceutical Science, Assam Down Town University, Guwahati, Assam, IndiaSachin Kumar JainOriental College of Pharmacy & Research, Oriental University, Ujjain Road Indore MP-452010, IndiaSaket Singh ChandelDepartment of Pharmacology, Dr. C. V. Raman Institute of Pharmacy, Dr. C. V. Raman University, Bilaspur-495113, Chhattisgarh, IndiaShiv Shankar ShuklaColumbia Institute of Pharmacy, Tekari, Raipur, Chhattisgarh, IndiaSokindra KumarKSCP, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, IndiaSunil MistryApex Institute of Pharmacy, Samaspur, Chunar, Mirzapur UP, India 231304Upendra S. BhadoriyaIPS Academy College of Pharmacy, Rajendra Nagar AB Road, Indore MP, IndiaVinod NautiyalDepartment of Pharmaceutical Sciences, Gurukul Kangri University Haridwar, Uttarakhand, IndiaVipinchandra Bhaskarrao PandeDepartment of Pharmacy, Mandsaur University, Mandsaur-458001, Madhya Pradesh, IndiaVishal TrivediDepartment of Pharmacy, Madhav University, Abu Road, Pindwara, Rajasthan, India

Origin of COVID-19

Aseem Setia1,Km. Nandani Jayaswal1,Ram Kumar Sahu2,*
1 Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab-142001, India
2 Department of Pharmaceutical Sciences, Assam University (A Central University), Silchar, Assam – 788011, India

Abstract

Coronavirus is a type of virus that is surrounded by non-segmented, single-stranded, positive-sense RNA genomes that reproduce in the cytoplasm. The size of the coronavirus is usually 80-120 nm. It was discovered in Wuhan, China in December 2019, and it was termed 2019 nCoV or COVID-19. The coronavirus is encased in a lipid bilayer and it possesses several proteins. These proteins are surrounded in the envelope of a virus; whereas, in the viral RNA, N-protein shows interactions and it can be found on the outer surface of the viral particle, forming the nucleocapsid. The spike protein is identified as the leading protein and mediates the entrance inside the host body that would cause SARS-CoV-2syndrome. The spike protein has two spheres namely S1 and S2. The receptor that is attached to the S1 and further S2 is responsible for fusion. In the past, the most severe types of virus which had resulted in large-scale pandemics were SARS (in 2002–2003) which occurred in Guandong Province, China. Meanwhile, Saudi Arabia had experienced the Middle East respiratory syndrome (MERS) in 2012. The virus in the 1960s was commonly identified in birds and mammals; mostly in rats, camels, cats and bats. SARS-CoV-2 causative agents belong to the genus β-Coronavirus. Coronavirus can be classified into four genera such as α, β, γ, and δ coronavirus. Alpha and beta coronaviruses are found in mammals such as bats. Gamma coronaviruses would primarily infect birds and affect mammalians, whereas delta coronaviruses would infect both birds and mammals. This chapter highlights the origin, historical background, the classification of the coronavirus as well as providing the conceptual information on various treatment approaches for COVID-19.

Keywords: β-Coronavirus, Coronavirus, MERS-CoV, SARS-CoV, SARS-CoV-2, Spike Protein.
*Corresponding author Ram Kumar Sahu: Department of Pharmaceutical Science, Assam University (A Central University), Silchar, Assam – 788011, India; E-mail: [email protected]

1. INTRODUCTION

Coronavirus is a chief pathogen that principally infects the respiratory tract of humans. Previous coronavirus outbreaks (CoVs) have shown syndromes of the

Middle East respiratory syndrome (MERS)-CoV as well as a severe acute respiratory syndrome (SARS)-CoV. These syndromes were alarming to the world’s population due to the infections they had caused [1]. SARS-CoV first appeared in 2002, followed by (MERS-CoV) and the novel coronavirus in 2012 and 2019, respectively. COVID-19, which was recently discovered, is the fifth known pandemic since the 1918 flu pandemic [2]. Coronaviruses are viruses enclosed with non-segmented, single-stranded, positive-sense RNA genomes that reproduce in the cytoplasm and they are typically 80-120 nm in size. COVID-19 was first identified in December 2019 in Wuhan, China, and was later referred to as 2019 nCoV or COVID-19 [3]. The SARS-CoV virus is a member of the Coronaviridae family, specifically the orthocoronaviridae subfamily and the order Nidovirales. The size range of the RNA genome lies between 26 to 32 kb. A helical nucleocapsid encompasses the DNA, which is surrounded by a lipid bilayer that is derived from the host [4]. Membrane (M), Spike (S), envelope (E) and nucleocapsid (N) are proteins found on the surface of the coronavirus (N). The S protein is the primary viral entry point [5]. The S protein is a large, Type-I transmembrane protein with 1160 amino acids for avian infectious bronchitis virus (IBV) and 1400 amino acids for feline coronavirus (FCoV). In the S protein, two domains namely S1 and S2 were discovered. The two domains S1 and S2 would recognize the host receptor and act for further fusion, respectively [6]. Once it is attached to the receptor, the envelop spike proteins would enter the host body directly through the cell surface and via the endocytosis fusion process. The massive conformational changes in the spike protein would determine the virus-host membrane fusion. Coronavirus has the appearance of a crown in an electron microscope and it is due to the presence of the glycoprotein spikes on its cover [7]. The MHV receptor was first discovered in 1991 and it was identified as the leading coronavirus binding receptor as it would allow the MHV to infect cells by binding them to the CEACAM1 molecule [8]. CEACAM1 is a part of the immunoglobulin superfamily and it is classified as a Type-I transmembrane protein. The multifunctional protein CEACAM1 plays a major role in the adhesion and cell signalling. Human coronaviruses consist of seven strains namely Human Coronavirus OC43 (HCoV-OC43), MERS-CoV, SARS-CoV (HCoV-NL63, New Heaven Coronavirus), Human Coronavirus HKU1, Human Coronavirus 229E (HCoV-229E), HCoV-EMC as well as the new strain that is identified as the Wuhan coronavirus which is known to be extremely dangerous and currently spreading widely worldwide (known as SARS-CoV-2 or COVID-19). Coronavirus Humanoid viruses, such as HCoV-229E, -NL63, -OC43 and –HKU1 are common in the humanoid population and they would display severe infection in the human respiratory tract at every age group. Alpha coronaviruses consist of HCoV-229E and NL63 while beta coronaviruses include OC43 and HKU1 [9]. The binary human viruses (HCoV-229E and HCoV-NL63) that are identified as the alpha coronavirus can infect animals and cause severe illness. The amino peptidase N (APN) protein is present in the host and acts as a receptor for HCoV-229E [10]. The Type II transmembrane protein CD13 is termed an APN protein that originates on the respiratory and intestinal epithelial cells. The APNs are Zn2+dependent proteases and they have the capability to break down the protein of N terminal neutral amino acids. Furthermore, the beta SARS-CoV is able to bind to the carbohydrates that are presented in a galectin fold-like structure found in the S1 NTD. The SARS-CoV was first discovered in 2002 and the (ACE-2) receptor was responsible for the virus [11]. Type I main membrane protein is a mono-carboxypeptidase that hydrolyzes angiotensin II and it is found in a substantial fraction of ACE2 receptors expressed in lung tissue. When a coronavirus infects the host, the calcium-dependent (C-type) lectins are predicted. Humans, mammals and birds are all afflicted by the coronavirus infection in humans as it affects the respiratory tract, the gastrointestinal tract, the hepatic system and the nervous system. Acute and persistent infections are both possible [12]. The α, β, γ, and δ are four different types of coronaviruses in which the alpha and beta are responsible for infections. Acute lung injury is caused by H5N1, SARS-CoV and H1N1 while acute respiratory distress syndrome (ARDS) could cause failure and death of the pulmonary region. The following are two possibilities that are likely to explain the creation of novel coronaviruses: a) natural selection in an animal host prior to and after zoonotic transmission and b) natural selection in humans after zoonotic transmission. Clinical types and risk factors are highly variable, resulting in scientific data ranging from asymptomatic to lethal. The basic symptoms of coronavirus include: cough, sore throat, breathlessness, fever, and the patient must be quarantined for 2-14 days after infection. Following the (H1N1), 1957 (H2N2), 1968 (H3N2) and 2009 Pandemic flu (H1N1), the WHO had declared a new coronavirus outbreak pandemic on March 11, 2020 [13] (Fig. 1).

Fig. (1)) A timeline of the five pandemics that have occurred since 1918 as well as the viruses that have remained circulating globally ever since.

2. Historical Background, Origin and the Transmission of Coronavirus

Coronavirus (CoV) was first discovered in the 1960s. The International Committee on the Taxonomy of the Coronavirus study group utilised relative genomics to evaluate and screen the replicative proteins in open reading frames as well as to differentiate and identify CoV at different cluster ranks [14]. CoV is linked with varying degrees of illness. In the past, SARS (in 2002–2003) and (MERS) (in 2012) had resulted to large scale pandemics. In the 1960s, the coronavirus was often found in animals and birds especially camels, rats, and bats [15] (Fig. 2). The taxonomy of coronavirus is as follows: genus -Coronavirus, family Coronaviridae, and order Nidovirales [16]. From 2002 to 2003, a similar virus was identified which had infected humans and it was discovered to be the cause of SARS. The COVID-19 infection is triggered by a virus containing a positive-sense RNA genome of 30 kb. The coronaviruses found in Manis javanica and Rhinolophus sinicusare said to have approximately 74% to 95% similarity with this virus [17]. A major source of coronavirus was found to be off the bat, out of which, a few of them had infected humans. Based on the current studies, the SARS and MERS viruses which were first discovered in 2002 and 2012, were transmitted zoonotically by bats that had used palm civets and camels as intermediate hosts. According to the latest studies, SARS-CoV-2 is a bat-adapted coronavirus that has transferred to humans via zoonotic transmission. The Malayan pangolin coronavirus has been determined to be 99% identical to a new coronavirus. The pangolin-CoV receptor-binding domain (RBD) differs from SARS-CoV-2 by only one amino acid; pangolins infected with COVID-19 have shown pathological symptoms which are similar to humans and their blood circulating antibodies are able to react with the SARS-CoV-2 spike protein [18].

Fig. (2)) Different viruses found in different mammals such as SARS virus in civet cat, MERS virus in camel and SARS-CoV-2 in pangolin or snake.

3. Classification of Coronavirus

Coronaviruses are viruses that belong to the Coronaviridae family which is the most important family in the Nidovirales order. The coronaviridae family is divided into two subfamilies: torovirinae and orthocoronavirinae, each of which consists of four genera: α, β, γ, and δ coronavirus [19]. CoVs are commonly found in humans and birds, but they can also be discovered in other animals (Fig. 3). Alpha and beta coronaviruses are found in mammals whereas birds and mammalian species would be infected through gamma coronavirus. Delta coronaviruses on the other hand would infect both birds and mammals. Animal CoV poses a substantial threat to livestock and it is suspected to be the cause of financial losses in domestic animals and birds. Moreover, animals can infect humans and spread infection through human-to-human transmission, which is uncommon [20].

Fig.(3)) Animal to human transmission of a virus is a rich source of ingestion of infected animals as well as coming into close contact with an infected person and the virus can be transmitted to a healthy individual.

3.1. Differences and Similarities Between SARS, MERS, and the nCoV-2019

3.1.1. Similarities and Differences

SARS-CoV was discovered in 2002 to 2003 and it was referred to as a Severe Acute Respiratory Syndrome. It occurred in Guandong Province, China with a total of 8098 cases identified and a death rate of 774 [21]. Coughing, shortness of breath, fever as well as other serious complications such as pneumonia and kidney failure were the symptoms of SARS-CoV. The incubation period would last from two to fourteen days. According to research, SARS-like CoVs were found in civets and raccoon dogs from the local Chinese markets. SARS-CoV was first detected in bats and small animals before it was transmitted to humans. Several SARS-CoVs have been identified in bats from various regions of China through research. Various studies have revealed that the ACE-2 receptors have an SARS binding affinity [22]. The SARS-CoV consists of the S protein, which has the highest binding affinity towards the ACE-2 receptor, which is found in human lungs and would eventually affect the airway epithelial. In 2012, MERS-CoV was identified in Saudi Arabia. The symptoms and incubation period of MERS-CoV were found to be similar to SARS-CoV [23]. MERS-CoV was detected in 27 countries, with an estimated total of 2506 cases and a death rate of 862. MERS-related CoVs (MERS-CoVs) were discovered in bats, suggesting that the dromedary camels had transmitted the MERS-CoV to humans. According to studies conducted, the camel MERS-CoV strain was known as the human MERS-CoV strain. MERS-CoV, like SARS-CoV, consists of S proteins that are harmful to humans [24]. MERS-CoV had a strong affinity for human DPP4, infected human cells and triggered the outbreak in 2012 [25]. As previously described, nCoV-2019 was discovered in Wuhan, China, and was later given the name of COVID-19. SARS-CoV-2, the third human CoV, would induce respiratory failure and had a similar incubation time to SARS-CoV and MERS-CoV infections [26]. Cases in China and around the world are on the rise since December 2019. Based on the patients’ samples, the nCoV-19 virus has been identified as a beta coronavirus. According to the findings of the study, SARS-CoV-2 is a new virus that is similar to SARS-CoV and MERS-CoV, in which both were found in bats [27]. The SARS-CoV-2 virus contains several proteins, one of which is known as the spike protein. The spike protein has the highest binding affinity for the ACE-2 receptor which would cause damage to the lungs' epithelial cells (Table 1).

Table 1Classification of human coronavirus.Classification of Human CoronavirusReferencesStrainHcoV-229EHcoV-OC43SARS-CoVHcoV-NL63HcoV-HKU1MERS-CoVSARS-CoV-2[28-34]Discovery1966196720032004200520122019[35-40]Genera-Lineageαβ-Aβ-Bαβ-Aβ-Cβ-B[41-47]Cellular ReceptorAminopeptidaseN (CD13)9-O-Acetylatedsialic acid(SA)ACE2ACE29-O-Acetylatedsialic acid(SA)DPP4ACE2[48-53]Natural HostBatsRodentsBatsBatsRodentsBatsBats[54-60]Breathing SymptomgentlegentleSeveregentlegentleSevereSevere

4. Structure of Coronavirus and Role of their Proteins

4.1. Coronavirus Structure

The SARS-CoV-2 virus has a spherical shape and it is composed of positive RNA viruses consisting of a single strand which comprises spike proteins on the surface of the virus. The coronavirus is a spherical virus with a crown-like structure [61]. The word corona means “crown” in Latin as the virus appears as a royal crown under an electron microscope. The coronavirus is encased in a lipid bilayer and consists of several proteins including S, E, M, and N [62] (Fig. 4).The proteins are situated on the surface of the virus; however, in the viral RNA, the N protein shows interaction with RNA and it is found in the viral particle's core, where it forms the nucleocapsid. The S protein is known as the leading protein due to its high binding affinity for the ACE-2 receptor, which is found in the human lungs [63]. The spike protein has two parts S1 and S2 which are produced by the breakdown of the S protein through the host furin-like proteases. These spike proteins are present on the viral particle. When compared to the other proteins in the viral particle, the M protein is discovered in large amounts whereas the E protein is found in extremely small amounts [64]. M protein provides the virus its shape and works with E protein to orchestrate virus assembly and the creation of mature viral envelopes, therefore, could explain the difference in abundance. E protein also assists in the release of viral particles from the host cells, among other things. During viral assembly, the N protein would bind viral RNA as it is necessary for viral RNA packaging into the viral particle [65].

Fig. (4)) Structure of coronavirus.

4.2. Spike Protein and its Drawbacks into the Host Body

The novel coronavirus can be transmitted through respiratory droplets, produced by coughing and sneezing. CoVs, the enveloped positive-stranded RNA virus family, are classified into three major genera or groups: α-CoVs (group 1), β-CoVs (group 2) and γ-CoVs (group 3) [66]. Based on the structure of SARS-CoV-2, they are made up of four proteins: S, E, M and N that encapsulate a single-stranded viral RNA. The spike tends to interact with the host cell receptors. The host cell protease divides the spike protein into S1 and S2, one of which is a transmembrane protease serine 2 (TMPRSS2) [67]. The S1 subunit's primary function is to attach to harmless receptors on the host cell, whereas the S2 subunits would facilitate the membrane fusion Fig.(5). Therefore, it is most likely that the first approach is to develop a vaccine, followed by developing monoclonal antibodies that would attach with the spike protein and inhibit human cell interaction. Another potential target is the transmembrane protease serine two, which is required for coronavirus entry and viral spread. According to recent protein studies, the SARS-CoV-2 has a strong binding affinity to the human Angiotensin Converting-Enzyme 2 (ACE-2) receptors, which may be used as a mechanism for SARS entry [68] (Fig. 6). Type 2 alveolar cells which are found in the respiratory tract, have a high expression of ACE-2 receptors. ACE-2 receptors on the other hand, are found in a wide range of extrapulmonary tissues, including the heart, kidney, endothelium, and intestine. As a result, the interaction sites between ACE-2 and the spike protein should be considered as a potential drug target. A natural flavonoid called Hesperidin has already been identified in recent computational studies as a compound that is expected to bind with the binding interface of the spike ACE-2 complex [69]. According to the studies, spike proteins have the highest binding with the ACE-2 receptor, which could lead to severe lung injury.

Fig. (5)) Three coronavirus genera or groups' spike proteins. Fig. (6)) The coronavirus has several types of proteins on its surfaces, including S, E, M, N, as well as the spike protein, which is the leading protein of the coronavirus which would bind with the host cell receptor. The spike protein is chopped into two domains, S1 and S2, and one other protein is the transmembrane protease serine 2 (TMPRSS2). The presence of ACE-2 receptors in type 2 alveolar cells can be found in the respiratory tract. As a result of the study, it is clear that the coronavirus binds to the ACE-2 and the ACE-2 down-regulates the receptor, contributing to severe lung injury.

5. MECHANISM OF VIRAL ENTRY

The coronavirus is a huge class of viruses; it is not one specific illness; they are giant enveloped RNA viruses with a large RNA genome that can cause the (SARS) syndrome [70]. The coronavirus diagram depicts the viral entry and their involvement in various steps to damage the host cell. The host cell plasma membrane contains one protein receptor called CEACAM-1 which is responsible for the entry of novel coronavirus inside the host body (Fig. 7). With the spike proteins around the virus, they would bind to the CEACAM-1 and facilitate the receptor-mediated endocytosis, which would attract the virus to the host cell via conformational changes and adaptation in the plasma membrane [71]. Once the uncoating occurs, these proteins would move and the content of the virus is released into the genomic RNA host cell cytoplasm. This genomic RNA is known as a genomic RNA positive and it is nearly 30,000 nucleotides long. Then, the host cell machinery namely ribosomes would translate this genomic strand into two polyproteins, which are also known as polyprotein1a and polyprotein1b [72]. Consequently, numerous non-structural proteins would be obtained from the breakdown of the polyprotein which includes the RNA-dependent RNA polymerase (RdRp), helicases and non-structural proteins (nsp3, nsp4, nsp6) [73]. It has been stated that the non-structural protein would initiate the multiplication of the coronavirus. The replication of the coronavirus takes place in the endoplasmic reticulum membrane conscription to form double-membrane vesicles that are known as DMV. The RdRp and helicase which are localized within the DMV drive the production of sub-genomic RNA [74]. The entire sense RNA would undergo two events. Firstly, it can replicate back into sense RNA, which is exactly the same scenario during uncoating in the original virus. Secondly, a complete sense RNA can be transcribed by using a method known as discontinuous transcription in which a complete sense RNA can be produced. Furthermore, it could transcribe a slew of different RNA, all of which are truly mRNA that should be translated into different proteins, thus resulting in the formation of N copies of proteins from a single RNA. After synthesis, transmembrane structural proteins S, M, and E are inserted and folded inside the E.R before they are transported into the Golgi (ERGIC) compartment [75]. To form a nucleocapsid, the N proteins would bind to the viral genomic RNA inside the cytoplasm. Once the final virion gathering occurs in the intermediate compartment that is known as ERGIC, the mature virion is exocytosed into the smooth-walled vesicles and releases the viral progeny which matures the coronavirus to infect other cells [76].

6. Modes of Transmission

The transmission of novel coronavirus is preferably administered via normal routes which include a close contact with the infected person as well as direct transmission and airborne. Some of the common modes of transmission include sneezing and coughing, continuous acts of touching the face, nose and eyes (Fig. 8). Viral shedding occurs from the respiratory tract, saliva, feces and urine, resulting in the spread of the virus to other locations. The viral load is greater and lasts longer in patients with severe COVID-19. COVID-19 also has been reported to spread from infected patients to health care workers and flight attendants who were in close contact with them [77].

Fig. (7)) The mechanism of coronavirus is depicted in the diagram; the coronavirus contains various types of proteins, the leading protein is known as the spike protein; the spike protein enters the host body and attaches to the CEACAM-1 present in the host cell, and through conformational changes, receptor-mediated endocytosis would occur and the virus is released towards the genomic RNA and translate this genomic strand into two polyproteins and many non-structural proteins. Non-structural proteins such as RdRp and helicase are localized into the DMV and drive the production of sub-genomic RNA from which structural and accessory proteins are produced in the next phase of translation. Then, from one RNA N copies of proteins form, the transmembrane structural proteins would enter the ER and are transported into the Golgi compartment and the mammalian cell nucleus. Fig. (8)) Modes of transmission of COVID-19.

7. TREATMENTS OF COVID-19

A large number of populations around the world have suffered from novel coronavirus. As such, various pieces of evidence have suggested that there is a lack of concrete proof for effective antiviral treatments for COVID-19 [78