Coronaviruses: Volume 1

Jean-Marc Sabatier

• Publisher: Bentham Science Publishers
• Year: 2021
• Print ISBN: 9789811498947
• eBook ISBN: 9789811498961
• Topic: Medicine
• Subtopic: Infectious Diseases

In this difficult period of the SARS-CoV-2 (and its variants) infection responsible for Covid-19 diseases, the importance of scientific works and reviews dealing with these viruses has never been more essential and vital. Reports as of 20th April 2021 indicate over 141 million cases of SARS-CoV-2 infection worldwide (with over 3 million deaths recorded). This volume brings together essential data regarding prevention (vaccination), detection, and various approaches (chemotherapeutic drugs and antibodies) to the potential treatment of coronavirus infections. It presents six chapters concerning the following topics: (1) the resistance to the spread of SARS-CoV-2 and related Covid-19 diseases within a population based on the pre-existing immunity of a high proportion of individuals as a result infection or previous vaccination (2) the impact of the Covid-19 pandemic for the South Asian Association for Regional Cooperation (SAARC) region, comprising the Bangladesh, Bhutan, Maldives, Nepal, Pakistan, Sri Lanka, India, and Afghanistan (3) the effect of candidate drugs chloroquine and hydroxychloroquine on QT interval in infected patients with Covid-19 diseases (4) the antiviral potential of herbal-based immunomodulators (5) the humoral immune response in humans based on anti-SARS-CoV-2 antibodies to treat Covid-19 diseases (6) the various methods and strategies for diagnosing SARS-CoV-2 (and its variants) infection in hosts/humans. This compilation should prove to be a tool of crucial importance for researchers around the world working on research revolving around coronaviruses, as well as for clinicians confronted by a growing number of patients with COVID-19.

Neutralizing Antibody-Based Therapies against COVID-19

Hilal Çalık¹, Rabia Yılmaz¹, Hatice Feyzan Ay¹, Betül Mutlu¹, Rabia Çakır-Koç^{1, 2, *}

¹ Yıldız Technical University, Faculty of Chemical and Metallurgical Engineering, Department of Bioengineering, Istanbul, Turkey

² Health Institutes of Turkey (TUSEB), Turkey Biotechnology Institute, Istanbul, Turkey

Abstract

The novel coronavirus infection (COVID-19) that emerged from Wuhan, China in December 2019 caused a global health crisis. With confirmed cases worldwide exceeding 40 million and continuing to grow, many research groups have been working to develop therapeutics and vaccines against COVID-19. In fact, some vaccine candidates are currently being tested in the clinical phase. The primary target of most of the studies is the spike glycoprotein of the SARS-CoV-2 virus, which binds to ACE2 receptors and allowing the virus entry to the host cells for the initiation of infection. Drugs such as Hydroxychloroquine and Favipiravir only aim to minimize symptoms but cause severe side effects in patients. On the other hand, neutralizing antibodies represents an important strategy for the treatment of COVID-19. Therapeutic neutralizing antibodies against SARS-CoV-2 spike protein can induce antibodies to block virus binding and fusion, thus inhibiting viral infection. Clinical studies show that antibodies obtained from plasma of recovered patients can improve prognosis and increase the survival rate. However, obtaining a high amount of plasma-based antibodies is a major problem in practice, therefore there is an urgent need to develop and produce reliable, high-yield, and specific antibodies against COVID-19. Instead of convalescent plasma therapy, monoclonal antibodies, and other antibody-based therapies such as IgY antibodies, camelid antibodies/nanobodies offer a promising alternative. In this chapter, a perspective on antibody-based approaches currently developed against SARS-CoV-2 by given some fundamental knowledge about these neutralizing antibodies and their potential for the treatment of COVID-19 is presented.

Keywords: Camelid antibodies, Convalescent plasma therapy, IgY antibodies, Monoclonal antibody, Neutralizing antibodies, SARS-CoV-2.

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^* Corresponding Author Rabia Çakır-Koç: Yıldız Technical University, Faculty of Chemical and Metallurgical Engineering, Department of Bioengineering, Istanbul, Turkey and Health Institutes of Turkey (TUSEB), Turkey Biotechnology Institute, Istanbul, Turkey; Tel: [phone]; Fax: [phone]; E-mail: [email protected]

INTRODUCTION

The new coronavirus, SARS-CoV-2, which emerged in Wuhan, China's Hubei province, in late December 2019, spread to many countries in a short time and became an international pandemic affecting the whole world. According to the World Health Organization, the pandemic affected over 40 million people in the world and caused the death of more than 1 million people.

COVID-19 can cause different clinical manifestations ranging from asymptomatic disease to fatal disease [1]. The disease may initially show little or no symptoms. Typical symptoms of COVID-19 are fever, sore throat, cough, fatigue, shortness of breath, weakness, and muscular pain, however, new symptoms are reported every day such as loss of the sense of smell because the clinical outcomes of the disease have been clarified yet [2]. The disease is usually transmitted through respiratory droplets, hands, or surfaces contaminated by the virus and the incubation period of the disease is generally between 3-14 days [3].

Experimental and clinical studies of antiviral drugs (such as remdesivir, chloroquine, hydroxychloroquine, ritonavir), convalescent plasma transfusion, and vaccine formulations against COVID-19 disease have been ongoing. The safety of some antiviral drugs such as favipiravir and remdesivir used in the treatment of the disease is not certain and clinical studies are still ongoing [4]. Another treatment option is plasma transfusion from the recovered patient, but the difficulty in obtaining plasma during recovery and limited resources (donor) make clinical application difficult [5]. Drug and vaccine studies against COVID-19 disease are a key strategy both to prevent widespread viral infection and to reduce morbidity and mortality [2].

Currently, more than 230 vaccine candidates are in pre-clinical and clinical development to prevent SARS-CoV-2 infection [6]. On December 11, 2020, the first vaccine for Covid19 disease, the Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccine (Pfizer, Inc; Philadelphia, Pennsylvania) had been approved by the Food and Drug Administration (FDA) with Emergency Use Authorization (EUA) [7]. Moderna COVID-19 (mRNA-1273) vaccine (ModernaTX, Inc; Cambridge, Massachusetts) is the second mRNA vaccine approved by the Food and Drug Administration (FDA) with Emergency Use Authorization (EUA) on December 18, 2020 [8]. Also, an adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), developed by a group from the University of Oxford is currently being evaluated in phase II/III efficacy trials [9]. In today's drug and vaccine studies, new molecular biotechnological methods are more preferred in order to obtain products that are therapeutically more effective with fewer side effects [10]. Since the ‘90s, with the development of recombinant gene technology and molecular immunology, antibodies created against various diseases in vitro or in vivo have been humanized by gene engineering. The binding kinetics of antibodies have been increased and the ability to work in coordination with the immune system in a physiological environment has been gained. Because of these developments, antibody-based therapeutic applications gain important potential in clinic studies [11]. Antibody therapy, one of the fast and effective treatment in contrast to the traditional vaccine approaches, against SARS-CoV-2 offers a promising strategy in the control of the pandemic in terms of prophylactic and therapeutic purposes.

Coronaviruses consist of 4 main protein domains structurally; the surface spike (S) glycoprotein, the membrane (M) protein, the small envelope (E) glycoprotein, and the nucleocapsid (N) protein [12]. The spike (S) glycoprotein on the surface of the SARS-CoV-2 has an important role in the viral entrance [13]. In recent studies, it has been proven that the S protein of the SARS-CoV-2 virus is more likely to bind to the ACE2 receptor than other coronavirus types which cause the new coronavirus to spread faster among humans [14]. The S1 subunit of the S protein binds to angiotensin-converting enzyme 2 (ACE2) receptors, which are commonly found in respiratory system cells. The S2 subunit of the S protein mediates the fusion of the viral membrane to the host cell membrane [1]. Thus, blocking the S protein, which has an important role in the entry of the virus into the cell, with neutralizing antibodies is one of the main strategies of antibody therapies [15]. S1 subunit, particularly the S1-RBD, S1-N-terminal domain (NTD), and S2 domain has been the main target of neutralizing antibodies due to their high functionality in infection of the virus [16].

In this chapter, a perspective on neutralizing antibody approaches based on monoclonal antibodies, convalescent plasma antibodies, IgY antibodies, and camelid antibodies and their potential for the treatment of COVID-19 are presented.

Convalescent Plasma Therapy

Immune or convalescent plasma means plasma collected from recovered individuals with high titers antibodies. Convalescent plasma contains antibodies and proteins against the pathogen. Convalescent plasma therapy (CPT) is the administration of blood plasma taken from people recovered to individuals suffering from the same disease [17, 18]. The concept of CPT was created in the 1880s against diphtheria and tetanus toxins by using antibodies obtained in the blood of actively infected animals [19, 20]. After that CPT has been used for over a century. In the early 1900s, the use of CPT for infectious diseases such as poliomyelitis, small measles, and mumps was studied [21^-23].

In the mid-1900s, a high concentration of immunoglobulins purified from recovered human donors has provided the option of treating serious infectious diseases [24, 25]. In the following years, the development of various passive antibody therapies has allowed its use for the treatment of primary immunodeficiencies, autoimmune, and cancer diseases as well as infective diseases [26]. However, the lack of time and resources for the production of these passive antibody therapy products in emergencies such as epidemics has brought convalescent plasma therapy back to the agenda as an experimental therapeutic treatment as far as the development of effective drugs or vaccines [18].

It is thought that immune plasma/convalescent plasma therapy produces therapeutic effects in patients through variou...

Table of contents

• Welcome
• Table of Content
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• List of Contributors
• Effect of Chloroquine and Hydroxychloroquine on the QT Interval in Patients with COVID-19: A Systematic Review
• COVID-19: Impact of Pandemic on SAARC Nations
• Neutralizing Antibody-Based Therapies against COVID-19
• Antiviral Potential of Immunomodulators Based Medicinal Plants against Novel Coronavirus-19: Against the Pandemic
• Diagnostic Measures for COVID-19: Current Status and Advances
• Herd Immunity: An Indirect Protection Against COVID-19