Book Volume 2
Page: i-i (1)
Author: Zahir Shah
Page: ii-iii (2)
Author: Kamal Niaz and Muhammad Farrukh Nisar
Page: iv-vi (3)
Page: 1-19 (19)
Author: Aadil Javed*, Kamal Niaz and Ovais Sideeq
Previous severe acute respiratory syndrome-coronavirus (SARS-CoV) outbreaks resulted in a cohort of preclinical studies that utilized various mice models for determining the pathogenesis of the infection, including the viral replication, spread, and mortality of the disease. Such studies have provided a framework upon which new investigations have been launched for understanding the outbreak of new coronavirus disease-19 (COVID-19) causing viral agents and their interaction with the host and its body. Recent investigations showed that the previous SARS-CoV and the recently discovered severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) both require the spike S protein to enter the host cell upon infection the binding with the receptors on the surface of the cells. The viral entry also requires proteases from the host cells. Since there are key similarities between the structure of the viruses and the construct of the viral transmission along with the spread inside the host's body in animal models. They were developed for the previous viral agent. The disease can be emulated or manipulated to bring forth novel investigations leading to key data that can broaden the sphere of COVID-19 studies being conducted. There are several different options to choose the right animal model for the question being raised in the experimental design with the pathogenesis of COVID-19. This chapter focused on the already established animal models for other coronavirus outbreaks and some of the strategies that can be exploited to develop new animal models. For COVID-19, research aimed at targeting the therapy or basic investigations for understanding cellular or organ level mechanisms involved in the disease.
Page: 20-51 (32)
Author: Sonali Bajaj, Neha Sharma, Abhinav Anand, Devesh Tewari and Navneet Khurana*
The recent emergence of the novel betacoronavirus, pathogenic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) with high nucleotide identity to SARS-CoV represents the causative agent of a potentially deadly disease coronavirus disease-19 (COVID-19) in Wuhan, China, and spreading across several countries globally pose a great global public health concern. Until a vaccine is available, effective therapy must be identified, and many clinical trialshave been executed worldwide. Various in vitro investigations are ongoing using different cell cultures to find alternative treatment options, allowing SARS-CoV-2 replications. Various cell lines are susceptible to the SARS-CoV-2 infection. In this chapter, literature regarding SARS-CoV-2 isolated in several cell lines commonly used for diagnostic or research purposes has been summarized. It also shows that SARS-CoV-2 can achieve high titers in various cell cultures derived from different species. In addition, these cell lines are extensively used in the diagnosis, to study pathophysiology, genome studies, and the finding of new targets for drug development and provide new ideas for the discovery of lead compounds with potential therapeutic agents against novel COVID-19.
Page: 52-71 (20)
Author: Muhammad Mazhar Ayaz*, Ihtisham Ulhaq and Kashif Rahim
The recent emergent coronaviruses in the 21st century, such as Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV), Middle East Respiratory Syndrome- Coronavirus (MERS-CoV), and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has caused significant morbidity and mortality around the world. The lung is the most affected organ in the infection of human pathogenic coronaviruses. There is always a scarcity of human signs, symptoms, and modes of transmission. So to study the viral pathogenesis and evaluated interventions of therapies and vaccines, animals need to be used as models, especially at early epidemics. Lesions scoring can be identified from histopathological studies, and it can be helpful to understand the viral pathogenesis and damages to the cells to design effective therapies or vaccines. Histopathology uses the cells to determine viral host receptors and viral host tropism to relate with disease severity and lesions. Moreover, histopathology also plays a role in the qualitative description of affected organs to determine the micro-anatomic location of cells, type of cells, and cellular consequences during and post-infection. Comparatively, this approach has various limitations, but still, it is significant in comparing treatment groups. In comparing various groups, semi-quantitative and quantitative tissue scores are used for statistical analysis to increase the reproducibility of the study. This chapter refers to different features, including the importance of histopathology, principles, technique, scoring methods, and pathological characteristics of COVID-19, which can be valuable to assess the lung infection caused by SARSCoV- 2 and animal models and real situations.
Page: 72-104 (33)
Author: Amjad Islam Aqib*, Iqra Muzammil, Qaisar Tanveer, Tean Zaheer and Aisha Mahmood
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a novel member of the Coronaviridae family that is the causative agent of coronavirus disease- 19 (COVID-19), which is now pandemic in the world. Various proteins characteristically responsible for pathogenesis are categorized as structural proteins (S, M, E, and N), non-structural proteins, and accessory proteins (ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10). Substitution of 380 amino acids and mutations in SARSCoV- 2 compared to other SARS-like coronaviruses characteristically plays a key role in entering the development of infection. S1/S2 of S protein has a specific differential role in SARS-CoV-2 stabilization and resultant infection. In addition to these key proteins, the host and virus-related proteins play risk factors in the spread of this disease. The current chapter will describe the structure of key proteins, their role in pathogenesis, starting from viral attachment leading to the infection in the host compared to the viruses belonging to Betacoronaviruses.
Page: 105-143 (39)
Author: Amjad Islam Aqib*, Iqra Muzammil, Qaisar Tanveer, Sana Muzammal, Amna Ahmad, Firasat Hussain and Kashif Rahim
Differential diagnosis is a key step to treat and prevent any disease at current. Differential identification becomes more inevitable in diseases that become pandemic while their signs and symptoms overlap with many diseases. Coronavirus disease-19 shows resemblance in its pneumonic presentation with related coronaviruses (SARS virus, and MERS virus), adenovirus, influenza virus, human Metapneumovirus, parainfluenza, Respiratory Syncytial Virus, rhinovirus, bacterial pneumonia (Streptococcus pneumonia, Haemophilus influenza pneumonia, Moraxella catarrhalis pneumonia, and Chlamydia pneumonia), and Mycoplasma pneumonia. Contrary to the discussion of only diagnostic findings, a comprehensive approach of differences in aetiologies, transmission/epidemiology, pathogeneses, clinical signs, and response therapy is necessary to resolve pandemic corona infection. Additionally, mathematical predictive models calculate the reproductive number (R0) to show the epidemic nature of the disease in comparison to other conditions, thus aids therapeutic and prevention measures. The current chapter differentiates minor and major differences of COVID-19 compared to viral and bacterial diseases that show similar signs and symptoms.
Page: 144-174 (31)
Author: Iyad Ibrahim Shaqura, Ahmed Abdelmajed Alkhodary, Abdullah, Muhammad Ibrar and Fazlullah Khan*
The outbreak of coronavirus disease-19 (COVID-19) across the world has caused serious health issues in terms of physical and psychological damage to human health. The spread of this virus was rapid and shortly spread to almost every country in the world. Due to the high infection rate and occurrence of complications in the infected individuals, the research and development of anti- COVID-19 drugs became the utmost necessity of time as no specific drug is available to relieve the clinical symptoms of COVID-19. We reviewed reliable information on targeted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) candidate drugs in the present chapter. Also, we summarized novel insight into the future development of safe, effective, and less-toxic antiviral drugs available and employed for the management of COVID-19. Similarly, we focused on antiviral medications under investigation for this purpose; several medications with different mechanisms of action were noticed for the treatment of COVID-19.
Page: 175-191 (17)
Author: Afshan Shafi, Kashif Akram, Ismail Shah and Fazlullah Khan*
Novel coronavirus disease-19 (COVID-19) is the deadliest form of coronavirus, which has caused pandemics across the world. According to a recent survey of the World Health Organization (WHO), by August 8, 2020, shows around 19187943 cases and 716075 deaths from this virus globally. In addition to the shortage of effective drugs and vaccines, the outbreak of COVID-19 triggered by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) prompted the medical community to scramble for new antiviral formulations. Mankind utilizes the plants' origin medicines from ancient to treat and cure various diseases. They are the best possible tools to tackle the disease as they have the lowest possible side effects compared to other forms of drugs available and in use to treat the diseases. Several phytochemicals extracted from plants could provide a baseline for research into plant extracts in treating and preventing coronavirus. The present chapter aims to summarize phytochemicals' effectiveness against COVID-19.
Page: 192-218 (27)
Author: Muhammad Farrukh Nisar*, Ahmad Uddin, Kamal Niaz, Shaukat Hussain Munawar, Qudratullulah, Faisal Siddique, Muhammad Yasir Waqas and Ahmad Farooq
The ongoing outbreak of coronavirus-19 (COVID-19) has quickly become a daunting challenge to global health. The ultraviolet radiations (UVR) A wavebands fall in the region of 320-400 nm of the solar spectrum and comprise about 95% of overall ultraviolet (UVs) approaching the biosphere. The UVA is extensively used in phototherapy systems, as a disinfectant, and in various skin-related conditions. This chapter aimed to address the reduction of coronavirus replication by direct application of phototherapy (UVA) in lungs and modulation of nitric oxide (NO) in skin cells following UVA exposures. This NO influx inside the bloodstream to deliver into the lungs endothelial cells where it goes to incur cytoprotection to alveolar lung cells. Moreover, it is also proposed for direct application of therapeutic doses of UVA light inside the lungs. It uses a fiberoptic adapter to modulate the production of NO in lung endothelial cells, which will diffuse into the bronchi and lungs to leave bronchodilatory and vasodilatory effects. How NO reduces inflammatory burst and reactive oxygen species (ROS) in the lungs' alveolar cells is also discussed. Moreover, it is also proposed that UVA radiation application should be limited to physiological doses and applied every 4-8 h, with at least 24 h of therapy before reassessment. The treating physician should determine discontinuation of this direct UVA treatment into the lungs following observation of the patient's condition and the safety and efficacy of the treatment. This study will highlight and emphasize the importance of utilizing UVA radiation to control this epidemic.
Page: 219-252 (34)
Author: Laiba Hassan, Muhammad Ali Syed* and Mohammad Ejaz
Coronavirus disease-2019 (COVID-19) first originated from China, named Wuhan, and now becomes a pandemic disease. The COVID-19 infections range from asymptomatic to mild and severe conditions. Medicinal plants have potential therapeutic effects for different infectious diseases and have long been used to treat many diseases. Wild plants are well-known for their anti-viral activities and are also used in herbal treatment for COVID-19 infection. Various traditional medicine systems use plants for the treatment of COVID-19. The considerable therapeutic effect was achieved by using traditional Chinese medicine (TCM) during the 2003 outbreak of severe acute respiratory syndrome (SARS), which brought new hope preventing and treating COVID-19. The Ministry of Ayurveda, Yoga & Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) focuses on prophylactic treatment, dietary management, and simple traditional remedies for the treatment of symptoms of COVID-19 by using medicinal plants. Telemedicine was focused on a new health care model to prevent transmission of COVID-19 by avoiding person-to-person contact. The purpose of this chapter is to identify the effective herbal treatment for COVID-19.
Page: 253-265 (13)
Author: Muhammad Ibrar, Abdullah, Iyad Ibrahim Shaqura, Ahmed Abdelmajed Alkhodary and Fazlullah Khan*
Historically, convalescent plasma (CP) has been successfully used in pandemics caused by the influenza A (H1N1) virus, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola. As the current pandemic by SARS-CoV-2 poses an unprecedented threat to humanity. The number of infections is increasing exponentially day by day. Identifying, qualifying, collecting, and preparing plasma from convalescents with sufficient SARS-CoV-2 neutralizing antibody titers in this pandemic may be challenging but within the approach of most blood establishments. Careful clinical evaluation may rapidly establish whether CP therapy at the early onset of disease in patients of high risk may improve symptoms, reduce hospital stay and decrease mortality due to COVID-19. Moreover, CP is an excellent therapeutic option due to the lack of specific treatment for COVID-19, as the availability of anti-viral drugs/vaccines may take more time.
Page: 266-287 (22)
Author: Ovais Sideeq*, Kamal Niaz, Kashif Rahim and Aadil Javed
Stem cells have long been a topic of interest around the globe. Now and then, stem cells are being studied for revealing their beneficial effects. Countries around the world are in a race in stem cell research. Stem cells possess some unique and considerable qualities that hardly any other cell to date has. The outbreak of novel coronavirus or coronavirus disease-19 (COVID-19) was located in Wuhan, China. After a few months, the episode was declared Pandemic by the World Health Organization (WHO) as it engulfed many countries worldwide. Since then, stem cells have gained more push in clinical as well as pre-clinical stage research studies. COVID-19 shares some molecular properties with other coronaviruses like severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). Stem cells surprisingly showed some good outcomes in many patients infected with COVID-19. A lot of laboratory evaluation is being carried out to check the feasibility of different stem cells to be used in COVID-19 infected patients. This chapter discusses and highlights the possible interventions in COVID-19 using different lineages and bio-cultured stem cells.
Page: 288-313 (26)
Author: Zahid Manzoor*, Shaukat Hussain Munawar, Muhammad Farrukh Nisar, Muhammad Yasir Waqas and Muhammad Mazhar Munir
Computational approaches efficiently design the drugs to prevent diseases for which no drug is available. These techniques are also used for the development of new drugs. It involves using a variety of computer software for drug modeling and simulation, hence usually known as computer-aided drug designing (CADD). The computational tools provide crucial drug designing in a short period. These techniques are time and cost-effective as compared to conventional drug development methods. Computational methods can effectively model the suitable drug candidate by optimizing ligand-target interactions and observing the deep insight of cellular processes by its powerful tools. Several studies have applied these modern computational techniques to find out the possible therapy against the pandemic disease of COVID-19. The critical proteins of COVID-19, including 3C-like protease, papainlike protease, and RNA polymerase, are targeted to model the effective drug. CADD approaches suggest anti-viral drugs, anti-coagulant, anti-HIV drugs, and anti-fungal drugs to have little effect against COVID-19. This chapter aims to overview the different CADD approaches to design the possible drug for the treatment of COVID- 19.
Vaccine Development, Advantages, and Disadvantages of Group Immunity and Future Perspective for COVID-19
Page: 314-336 (23)
Author: Abdullah, Maqsood ur Rehman, Fazlullah Khan* and Tapan Behl
Since its outbreak in late 2019, SARS-CoV-2 has infected millions of people and caused 432, 204 deaths across the globe up to June 14, 2020 (WHO website). SARS-CoV-2 has a high transmission, prolonged incubation time, and an increased prevalence of asymptomatic infection. All over the world, the authorities are insisting on non-pharmaceutical interventions such as social distancing, imposing lockdowns, social isolation, and provision of personal protective equipment (PPEs) to the hospital and other essential departments. However, these measures have only slowed down the virus and cannot prevent rebounds on easing the restrictions. Moreover, the hype about the off-label use of drugs is on the rise. However, the efficacy and the risk of adverse effects have yet to be explored in clinical trials. Therefore, the only way to confer immunity and control the pandemic, the development of vaccines, is currently the research focus. The genetic sequencing of SARS-Cov-2 was done quickly, only in one month. To develop vaccines at pandemic speed, the scientific community faces the challenge of proof of clinical safety and efficacy. Moreover, the previous work is done, and scientists are utilizing the experience of SAR-CoV and MERS and the technologies thereof for COVID-19. Several manufacturers have announced their program and progress on vaccine development. Some vaccines have cleared phase I, and phase II clinical trials, while few are in phase III.
Page: 337-348 (12)
In this book volume-2 proposal has been classified into Part IV: Models for SARS-CoV-2 and Part V: Treatment Strategies for SARS-CoV-2. With the emergence of new coronavirus variants, epidemiology, different host tropism permits a thorough analysis of their evolution and acquired adaptability to their host which need different animal models and treatment approaches. No studies are complete without animal models closely related to human physiology to replicate the disease and observe the pathology conditions as in human cases. Such animal models play a vital role in virus pathogenesis and prepare a therapeutic immune response. Here describe bio-engineered transgenic mouse model inserting with specific genes, or CRISPR-Case9 gene-editing tool has been used previously for SARS-CoV and MERS-CoV. The chapter will deal with culture techniques or cell lines for COVID-19—also histopathology of COVID-19, essential proteins that up or down-regulate SARS-CoV-2. The last chapter of this part will describe other diseases having similar signs and symptoms and their differentiation. There is no specific treatment available to date, just symptomatic therapy. However, scientists will elucidate effective antiviral drugs in clinical trials, phytochemicals, photomedicine such as ultraviolet A & B, homemade remedies, blood plasma transfusion, stem cell therapy, and computational approaches in vivo and in vitro trials. This book will appear as a baseline for academicians, scientists, and health professionals as still, research is going to overcome this outbreak of COVID-19, the novelty of best animal models, and find an effective treatment. However, just a single book proposal like this wouldn't have flourished without enthusiasm and determined publishers' and investigators' strength to take time from their busy schedule and subsidize on time. We thank the whole investigators who contributed, directly and indirectly, to bring it to reality.