Coronavirus Disease-19 (COVID-19): Different Models and Treatment Strategies

Kamal Niaz, Muhammad Farrukh Nisar

• Publisher: Bentham Science Publishers
• Year: 2021
• ISBN:
  9781681089072
• Topic: Medicine
• Subtopic: Infectious Diseases

With the emergence of new coronavirus variants, epidemiology, host tropism presents an opportunity for a thorough analysis of their evolution and acquired adaptability to their host. These studies require 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 pathological conditions for comparison to human cases. Such animal models play a vital role in virus pathogenesis and prepare a therapeutic immune response in the organism studied. This volume focuses on two aspects of COVID-19 infection: Models for SARS-CoV-2 infection and Treatment Strategies for SARS-CoV-2 infection, respectively. Chapters in the first part describe bio-engineered transgenic mouse models with specific genes (including models created with CRISPR-Cas9 gene editing tools used previously for SARS-CoV and MERS-CoV), cell culture lines for COVID-19 studies and the histopathology of COVID-19. The section also includes a chapter covering essential proteins that up or down-regulate SARS-CoV-2 multiplication. The last chapter of this part describes other diseases having similar signs and symptoms and their differential diagnosis. The next section covers different treatment strategies for COVID-19. There is no specific treatment available to date, just symptomatic therapy. However, scientists have been testing antiviral drugs in clinical trials, phytochemicals, photomedicine such as UV A & B light, homemade remedies, blood plasma transfusion, stem cell therapy, and computational approaches in both in vivo and in vitro trials. This book serves as an ideal resource on these aspects of COVID-19 for academicians, scientists, and health professionals.

Part I: Models for COVID-19

Genetically Engineered Mouse Models for COVID-19

Aadil Javed^{1, *}, Kamal Niaz², Ovais Sideeq³

¹ Department of Biotechnology, Graduate School of Natural and Applied Sciences, Ege University, Bornova, Izmir, Turkey

² Department of Pharmacology & Toxicology, Faculty of Bio-Sciences, Cholistan University of Veterinary and Animal Sciences, Bahawalpur-63100, Pakistan

³ School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran

Abstract

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.

Keywords: COVID-19, Knockout, Mouse models, SARS-CoV-2, Transgenic.

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^* Corresponding author Aadil Javed: Department of Biotechnology, Graduate School of Natural and Applied Sciences, Ege University, Bornova, Izmir, Turkey. E-mail: [email protected]

INTRODUCTION

In December 2019, a novel coronavirus outbreak was reported in Wuhan, China which caused a pandemic and is an ongoing public health concern worldwide [1]. The disease known as coronavirus disease-19 (COVID-19) is caused by the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which leads to deadly pneumonia and severe health issues related to lung damage [2]. The genomic properties of the viral agent responsible for the local epidemic in China were timely shared across the scientific community. Since then, a valiant effort to combat the disease and understanding the agent responsible for the pandemic has been ongoing. Across the world, millions of people have been affected by the pandemic leading to a change in lifestyle globally [3^-5]. The diverse scientific community took upon understanding the pandemic and the viral agent responsible for the COVID-19 from the get-go during the earlier days of the pandemic in 2020 [6]. Millions of people have been infected, and hundreds of thousands of people have lost their lives due to the COVID-19 pandemic outbreak [7]. Various attempts have been reported to classify the epidemiological features of the pandemic, including the case fatality rate, reproduction number, and recovery rate. To date, it is being assumed that various factors that affect the rigorous testing and other socio-economic factors hamper any progress in determining the true features of the pandemic [8^-13].

The SARS-CoV-2 virus belonging to the Coronaviridae family of the virus has been studied extensively due to the urgency of pandemics. The vaccine development approaches have been challenging so far, and various mouse models have been utilized for understanding different aspects of the physiology of this novel coronavirus. Previously, the Middle East Respiratory Syndrome (MERS) and SARS candidates for vaccines were evaluated in the different mouse models [14, 15]. The clinical features, including the pathogenesis of the coronavirus, can be studied in great detail upon the development of animal models that can efficiently mimic the properties of the disease. For this purpose, numerous models have been developed in animals such as hamsters, guinea pigs, mice, cats, and rabbits, etc., [16^-20]. The major receptor of SAR-CoV is angiotensin-converting enzyme 2 (ACE2) and is utilized to develop transgenic mouse models containing the human ACE2 gene [21]. Rhesus macaques were the first animal model for vaccine development against MERS-CoV, showing the symptoms of the infections as seen in clinical patients [22]. Golden Syrian hamsters were also used as animal models for establishing the vaccine candidate's safety and viral pathogenesis for different strains of SARS-CoV [19]. NSP16 CoV attenuated vaccine development approaches utilized mice as well [23]. Developing animal models, MERS-CoV had several drawbacks due to the inefficiency of the virus being replicated in the respiratory system. Therefore, new approaches like gene targeting paved the way for demonstrating modified models containing genes of interest or lack thereof for more naturalized infectivity of the virus, e.g., human DPP4 transgenic mice [24]. Clustered regularly interspaced short palindromic repeats and associated protein 9 (CRISPR-Cas9) the system has been efficiently employed for developing mouse models that are engineered to get infected by the virus and show high replication [25, 26]. Small animals like rabbits and mice are used to develop mouse models specific for a particular infection such as SAR-CoV-2 for various reasons, including efficacy, cost issues, and manipulation approaches. There is still much work that is needed to better understand the behavior of COVID-19 and transgenic animal models can efficiently smoothen the process of understanding due to ease in receptor identification, protection, pathogenesis models and immune response studies [15, 27]. Various applications and interference points for different types of mouse models in understanding or combating SARS have been depicted in Fig. (1). The aim of this chapter is to summarize the well-known animal models that can be used for coronavirus along with some of the strategies that can be exploited to develop new animal models for COVID-19 as a model to target the therapy or basic investigations the underline molecular mechanisms involved in the disease.

Emerging Role of CRISPR/Cas9

In molecular diagnostics, CRISPR, and the C...