An Update on SARS-CoV-2: Damage-response Framework, Potential Therapeutic Avenues and the Impact of Nanotechnology on COVID-19 Therapy E-Book
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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
This update on SARS-CoV-2 focuses on basic knowledge about the virus and COVID-19 treatment. Chapters present basic information about the disease and its treatment. The virology, epidemiology, etiology, and damage response framework of SARS-CoV-2 are also discussed in detail.
The book also covers recent topics of interest to pharmacology scholars such as the immunopathogenesis of SARS-CoV2, nanotechnology, repurposed drug treatments, COVID-19 vaccines, and phytomedicine for COVID-19 therapeutics.
Readers in pharmacology, virology and medicine will find the book a simple, yet informative update on SARS-CoV-2 and COVID-19 treatment.
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Seitenzahl: 477
Veröffentlichungsjahr: 2002
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FOREWORD
Countless epidemics and pandemics have struck the world throughout history, claiming the lives of thousands to millions of people. Although we have progressed far ahead in our research and medical fields, the appearance and spread of the 2019-n CoV (SARS-CoV-2) virus by zoonotic transmission causing COVID-19 have posed several concerns to public health all across the world. The COVID-19 pandemic outbreak has proven to be a global calamity and unlike many others, claimed the lives of billions of people. It has posed several challenges to the health policymakers as well as the medical fraternity including the researchers. It has affected the socioeconomic status, globally. The first challenge is to deal with future outbreaks that may arise due to the emerging new coronaviruses or any other viruses of zoonotic origin. Future epidemics could be caused by newly developing coronaviruses or other zoonotic viruses. Therefore, apart from curbing these outbreaks, now there is a need to have a thorough understanding of zoonotic origin viruses to prevent future outbreaks. Now it is clear that our ability to deal with future epidemics will be determined by the efforts we take based on previous lessons learned from pandemics. Thus, in order to deal with future pandemics as well as the current viral pathogenic catastrophic scenarios, deep knowledge of the current COVID-19 pandemic is required.
Another big challenge is the development of vaccines to deal with new viruses and variants of SARS-CoV-2 itself emerging consistently causing havoc. Lastly, there is a challenge to find out not only the novel medicines, but also the treatment strategies for the management of the patients, especially for post-COVID complications that call for the understanding of the pathophysiology and possible targets for the same.
Although several books have been published worldwide, this is a unique book that provides a review of COVID-19, including information on virology, epidemiology, clinical signs, damage response framework, immune-pathological pathways, diagnostics, therapeutic choices, vaccine prospects, and more. It also explains the likely mechanisms of numerous effective medications for COVID-19 infection management. Despite the availability of a few vaccinations, several clinical research, and clinical trials against 2019-nCoV, COVID-19 remains an incurable menace. As a result, a specific emphasis should be made on studying COVID-19's viral etiology and pathophysiology, which is critical for better customizing and creating effective treatments and vaccines. In this book, the authors provided a great assessment of the full explanation of viral pathogenesis and pathophysiology of COVID-19, which may pave the road for future virologists to tackle future coronavirus epidemics.
In this book, the authors have also proposed practical ways to deal with those major challenges and also acknowledged the impact of potential and promising nanotechnology-based tools to circumvent future challenges in the diagnosis, treatment, and prevention of COVID-19. Possible potent therapeutic nanoformulations were addressed to accelerate the development of novel targeted nanoformulations for combating COVID-19. I am sure this book will provide directions to the future and current researchers in overcoming the challenges and will come out with novel solutions and products.
The material and scientific knowledge in this book shall allow readers to have a consistent and broad understanding of the primary concerns and their solutions in relation to the present COVID-19 pandemic.
PREFACE
The authors were inspired to write this book by a vision to provide the basic and core information regarding the novel and life-threatening coronavirus namely 2019-nCoV causing COVID-19, of which the entire world was completely unaware.
The COVID-19 pandemic outbreak has evidenced us to be an astounding catastrophe inflicting billions of lives around the globe. To date, it was reported that the third highly pathogenic human Coronavirus disease is COVID-19, which has posed a severe and serious threat to the entire world's socioeconomic, medical, and public health infrastructure.
Considering the present scenario, this book contains eleven chapters on different aspects related to COVID-19 and 2019-nCoV summarising what we have hitherto learned in the following key areas of virology, epidemiology, aetiology, damage response framework, pathophysiology, and diagnosis of COVID-19.
Several candidate-repositioning drugs have been proven with a record of both safety as well as efficacy profiles which have been widely used in some countries during the pandemic situation against 2019nCoV. Due to their pharmacological role and mechanism of action, some phytopharmaceuticals and immunomodulators are efficacious against 2019-nCoV and might be finding potential to combat COVID-19; all of which are discussed in this book in detail. This book also provides deep insights into the repurposed drugs, pharmaceutical intervention strategies, various treatments, clinical and research approaches, all authorised vaccines and nanotechnology tools that may fill the research gaps for the current COVID-19 management and future pandemic outbreaks of newly emerging 2019-nCoV variants.
To manage COVID-19 and curb the global spread of 2019-nCoV, knowledge of all of the above aspects is required. Hence, we compiled all of these elements into one book as separate chapters to present a valuable resource of information on COVID-19 for all of those who are involved in this coronavirology field.
This book in essence provides a grass-root level of knowledge about COVID-19 and 2019-nCoV. It is also a manual to guide future coronavirology scientists assisting them with future research ideas and approaches to combat new variants of 2019-nCoV as well as future outbreaks of coronaviruses.
We hope that you enjoy this book and find it useful.
List of Contributors
COVID -19 Overview
Anitha Sriram1,Pravin Medtiya1,Srushti Mahajan1,Rahul Kumar2,Dharmendra Kumar Khatri2,Shashi Bala Singh2,Jitender Madan1,Pankaj Kumar Singh1,*Abstract
The appalling COVID-19 pandemic outbreak has become a major cause of mortality in 2020. The COVID-19 is caused by a dreadful coronavirus called nCoV (SARS-CoV2). The term “coronavirus” (CoV) originates from the Latin term corona, which means “halo”/ “crown,” as the virus carries the crown-like projections (spikes) on its surface. Coronaviruses are a large group of viruses causing mild diseases to severe respiratory and gastrointestinal diseases. This review describes the overview of COVID-19, including the origin and reservoir of SARS-CoV2 and the genomic sequence of SARS-CoV2 compared to other coronaviruses. Furthermore, major events of the COVID-19 outbreak, reported confirmed cases, death cases, and case fatality rate (CFR) of covid-19 since its beginning until now, and different facts about fatally potential beta coronaviruses are also discussed in detail in this review.
INTRODUCTION
Generally, viruses cause infectious diseases. Current Severe Acute Respiratory Distress Syndrome-Corona Virus (SARS-CoV-2) was identified in China in 2019, which arose suddenly causing COVID-19, and within a short time, it became a global pandemic, thus making a serious public health concern. It made a global impact on health care and socio-economic development [1]. This COVID-19 became a major cause leading to mortality in the year 2020. Coronaviruses are a large group of viruses causing mild diseases to severe respiratory and gastrointes-
tinal diseases. Six species of human coronaviruses (HCoV) so far discovered are HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, SARS-CoV, and MERS-CoV.
Both SARS-COV and MERS-COV are the earlier CoVs that cause severe diseases in human beings. The foremost coronavirus that causes severe disease in human beings is SARS-CoV. SARS-CoV was identified in China at Foshan in 2003. The Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the second most coronavirus causing severe disease in human beings, as identified in Saudi Arabia in 2012 [2-5].
A novel coronavirus (nCoV) was identified in China in late December 2019, regarded as 2019-nCoV because it was identified in humans, which were never seen before. The international virus classification commission named this nCoV as SARS-CoV-2 [6]. It is a third human coronavirus to cause severe infections of the upper and lower respiratory tract, especially a condition of “Acute respiratory distress syndrome” (ARDS); hence it is regarded as SARS-CoV-2 [7]. SARS-CoV-2 is recently identified as the seventh HCoV known to cause sickness. Therefore, World Health Organisation (WHO), on February 11th, 2020, proclaimed that N-COVID-19 is a novel coronavirus infectious disease in 2019 and a nCoV called SARS-CoV-2 [6]. This N-COVID-19 infection is around three times as contagious as influenza. For everyone, 2019-nCoV has become renewed interest among many viral infections, as it became a global pandemic causing the severe disease COVID-19 in human beings. COVID-19 is 10 times deadlier than seasonal flu. Other bacterial co-infections may also occur during this COVID-19 infection.
ORIGIN OF SARS-COV-2
In December 2019, huge pneumonia cases were reported in China. While identifying the underlying cause for many cases of pneumonia, the scientists discovered the novel coronavirus. On December 31st, 2019, the first and foremost cause of a nCoV was identified in Wuhan City, Hubei Province, China [8]. The theory is that the coronavirus emerged from animal species to human beings (which is called zoonotic spillover) and then began spreading rapidly among humans. These coronaviruses prowl quietly in different types of species acquiring mutations and genetic recombination, often jumping from species to species in crowded animal markets (in China) confined to close spaces to reach very dangerous and lethal mutations that allow it to infect human beings. Novel coronavirus has emerged from the people who are associated with the seafood market and live animal market in the Wuhan city of China [1]. Starting from Wuhan of China, it emerged on an endemic scale and started spreading among all the countries of the world very rapidly; hence COVID-19 is regarded as a pandemic disease. On March 11th, 2020, WHO confirmed COVID-19 as a pandemic disease to create and implement a global response to limit the spread of this infectious disease.
RESERVOIR OF SARS-COV-2
The spread of transmission of SARS-CoV-2 (hereinafter, SARS-CoV-2 will be referred to as 2019-nCoV) is from animals to humans by the zoonotic spill-over process followed by human to human. BatCoV RaTG13 is the bat coronavirus identified formerly in Rhinolophus affinis from Yunnan province of China. The 2019-nCoV is more identical to BatCoV-RaTG13, with a resemblance of 96.2% at the genomic sequence level. The sequence similarities of both RBDs of BatCoV-RaTG13 and 2019-nCoV is 89.2% [9].
Rising evidence and connoisseurs are together concluding that 2019-nCoV had a natural origin in horseshoe bats. Likewise, SARS and MERS were also assumed to be originated from bats [6, 10-12].
Much of the literature review suggests that 2019-nCoV and other respiratory viruses, like SARS-CoVand MERS-CoV, have originated from bats, stating that they may be the natural reservoirs for them. This has led to the establishment of the novel idea about host (bats) emerging human pathogens. Therefore 2019-nCoV is assumed to arise from a natural primary host called to bat. However, many studies have demonstrated that 2019-nCoV has infected human beings through an intermediate host that may be either the snakes or the pangolins (pangolins are small mammals used for smuggling the goods in China) [13].
One of the principal claims made once in the Journal of Medical Virology publication was that snakes might be the first believable intermediate host, and pangolins may perhaps be the second believable intermediate host for 2019-nCoV [14]. Recent shreds of evidence suggest that pangolins probably catch the viruses during the process of being traded. Novel pangolin CoV genomes exhibit 91% nucleotide sequence homology with 2019-nCoV [15]. The sequence similarities of both RBDs of pangolin CoV and 2019-nCoV is 97.4% [9].
But still, the natural reservoir and intermediate host of 2019-nCoV remains unclear. Likewise, dromedary camel and palm civet cats are the intermediate hosts for MERS and SARS-CoV, respectively, as shown in Fig. (1) [16, 17]. Intermediate hosts thus obviously participate in the inter-species transmission of pathogenic virus beginning from primary reservoir bats to spread the terminal host humans.
Fig. (1)) Zoonotic spill-over process of COVID-19.GENOME SEQUENCE
The genome of 2019-nCoV exhibits similitude with the genomes of other coronaviruses isolated from different sources. Nucleotide sequence resemblance for 2019-nCoV with the nucleotide sequence of other viruses is 96.2% with bat originated virus, 91% with pangolin originated virus, 80% with SARS-CoV, 55% with MERS-CoV, and 50% with common cold coronavirus [6, 12, 18, 19]
MAJOR EVENTS IN THE TIMELINE OF THE COVID-19 OUTBREAK
The Fig. (2) concludes all the major events that happened worldwide related to the COVID-19 outbreak [20-24].
REPORTED CONFIRMED CASES, DEATH CASES, and CASE FATALITY RATE (CFR) OF COVID-19
CFR is calculated by the ratio of the number of confirmed deaths to the number of diagnosed confirmed cases in a given time. Hence, CFR is also called case fatality ratio/case fatality risk, ranging from 0 to 1 [25]. This value of CFR, when multiplied by 100, gives the percentage of CFR, which depends on many factors like age, pre-existing diseases (co-morbid conditions), smoking habit, sex, and immunity of the patient [26]. CFR is different from the death rate and infection fatality rate.
Fig. (2A)) Timeline events involved in the COVID-19 from its beginning until march 2020. (Source: Timeline of WHO’s response to COVID-19).Back toward the start of the pandemic, a few countries experienced a large number of deaths comparative with that of the infected populace (hence, higher CFR). COVID-19 testing cases have enhanced markedly when the awareness about the severity of this SARSCoV-2 pandemic outbreak was once known. As more cases are to be recognized as well as careful precautions were taken by people to avoid deadly infection, this subsequently made the death proportion to get lowered. Hence, making the pandemic CFR lower, as a very less cumulative number of deaths relative to a large number of cumulative confirmed cases. This is the reason why 2019nCoV is less deadly than previous major outbreaks like SARS, MERS, and Ebola. Nowadays, everyone is vaccinated with at least a single dose and this helps them for fighting against COVID-19 and is less prone to mortality risk, which also makes the CFR lower. As per Fig. (3), CFR is low for COVID-19 people, but it is infecting a large number of people due to its high infectivity rate. As of September 27, 2021, the cumulative confirmed cases of the whole world are 232,609,674 and the cumulative confirmed deaths of the whole world are 4,762,115. Hence the CFR is 2.047 (4,762,115/ 232,609,674)*100) as of September 27, 2021. As of July 18, 2022, the cumulative confirmed cases of the whole world are 563.63 million and the cumulative confirmed deaths of the whole world are 6.37 million. Hence the CFR is 1.130 (6.37 million/ 563.63 million)*100) as of July 18, 2022 [25].
Fig. (2B)) Timeline events involved in the COVID-19 since from April 2020 until march 2021.(Source: Timeline of WHO’s response to COVID-19).TYPES OF CORONAVIRUSES AND THEIR OUTBREAK IMPACT
Coronavirus
The name “coronavirus” (CoV) is originated from the Latin term corona which means “halo”/ “crown,” where the virus bears or fabricates with the crown-like projections on its surface [27]. These projections are referred to as spikes or peptomers, which almost look like cloves with head and stalk [26]. These outward protrusions of spikes give the crown-like appearance to virions. Simply it looks like a solar corona. At least 15 spherical spikes having a diameter of 9 to 12 nm are present on the surface of the virus. A positive sense single strand genomic RNA (+ssgRNA) is encapsulated in CoVs whose diameter ranges between 80 and 120 nm [28]. Among so far identified RNA viruses, Coronaviruses has the second-largest genomic size of 27 to 32 kb (kilobase) [29] and the first largest genomic size of 41.1 kb is attributed to planarian secretory cell nidovirus (PSCNV).
Taxonomy of Coronavirus
Coronavirus order, family, subfamily, genera, and species are displayed as shown below in Fig. (4) [30-32].
CoronaVirus
Realm: Riboviria
Order: Nidovirales
Family: Coronaviridae
Subfamily: Ortho coronavirinae
Genus: Alpha CoV, Beta CoV, Gamma CoV and Delta CoV.
Amongst them, alpha and beta types of coronaviruses cause infection in mammalian species. Gamma coronaviruses cause infections in avian species and whales. Delta coronaviruses cause infections in avian species, pigs, and other mammals.
Fig. (4)) Representation of taxonomy of family Coronoviridae.FACTS OF FATALLY POTENTIAL BETA CORONAVIRUSES
From the CoV genomes phylogenetic analysis, it has been discovered that 2019-nCoV belongs to the beta coronavirus genus of lineage B. Fatally potential beta coronaviruses (β-CoVs) are posing a severe threat to humans, since the beginning of the 21st century. The fatal diseases and their disease-related parameters spread by different harmful β-CoVs are discussed in detail as shown in Table 1 [24, 33, 34].
The 2019-nCoV shares similarity with SARS-CoV in terms of viral tissue tropism for the respiratory system and clinical symptoms. It shares the similarity in the case of protein fold with SARS-CoV, despite amino acid variation at a few key residues [6]. But the 2019-nCoV antigenicity is contrasting to SARS-CoV [36]. It is proved from a case study, where mice monoclonal antibodies (mAb) and polyclonal antibodies (pAb) that act against S1-RBD (receptor-binding domain) of SARS-CoV did not react with S1-RBD of 2019-nCoV and hence these antibodies fail to neutralize the spike protein [35]. This makes clear that 2019-nCoV pathogenesis is dissimilar to SARS-CoV pathogenesis. Not only that, even RBD of 2019-nCoV attaches to the receptor hACE2 (human Angiotensin-Converting Enzyme 2) with higher affinity approximately by 10-20 folds greater in comparison to RBD of SARS-CoV [37, 38]. Hence, it remained a challenge in the development of new therapeutic drugs against this novel emerging virus.
CONCLUSION
The 2019-nCoV has a high infectivity rate and attack rate, which is the reason why it became a global pandemic within a very less period. As this pandemic outbreak has emerged rapidly, it became uncontrollable and lead to the increased mortality rate exhibiting higher CFR in the early pandemic time. As the 2019-nCoV origin is found out and declared that it is contagious and spreading from virus-infected Chinese people, all the possible traveling routes of possibilities were blocked (both to and from China) to limit the spread of the virus. As the virus spread is due to the cause of droplet infection, social distancing, thorough cleaning of hands, and wearing masks are certain precautionary measures that are to be followed to limit the transmissibility of the virus. As common-cold virus and 2019-nCoV even though they belong to the same family, their severity is varied, that’s why symptoms of the COVID-19 have to be identified by oneself and should not be neglected to protect their lives by themselves and protecting others lives by isolating and quarantining themselves. Hence, knowing the facts about harmful potential beta coronaviruses and their pathogenic mechanisms will help scientists to formulate an effective vaccine and treatment. Therefore, a detailed understanding of the origin, causes of infection, transmissibility, symptoms, pathogenicity, severity, CFR, and reproduction number of COVID-19 gives the information to guide the correct way of approaching to tackle the COVID-19.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
Declared none.
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Anitha Sriram1,Ravindra Vasave1,Indrani Maji1,Rahul Kumar2,Dharmendra Kumar Khatri2,Shashi Bala Singh2,Neelesh K. Mehra1,Pankaj Kumar Singh1,*Abstract
The 2019-nCoV RNA genome is highly protected by its unique structure equipped with mechanistic spike proteins on its surface. Its RNA genome contains almost all 14 Orfs encoding for at least 27 proteins. An Orf is a part of genetic material that can undergo translation and produce proteins. Four structural proteins (SPs) likely spike (S), envelope (E), membrane (M), and nucleocapsid (N) are present in 2019-nCoV and afford its structure. In this chapter, we have discussed in detail the virology of 2019-nCoV including structural proteins (SPs), accessory proteins, non-structural proteins (NSPs), genomic structure, and its components. The role of SPs, accessory proteins, NSPs of 2019-nCoV is discussed and this review also explains, how the interaction of 2019-nCoV occurs with that of hACE2. Additionally, topics such as stabilization of virus-binding hotspots on hACE2 by 2019-nCoV, the role of thiol-disulfide interchanges in the interplay between 'S' protein and hACE2, and the similarity (in terms of amino acid sequence homology) (%) of 2019-nCoV with SARS-COV are discussed.
