به‌روزرسانی درباره SARS-CoV-2: چارچوب آسیب-پاسخ، راه‌های درمانی بالقوه و تأثیر نانوتکنولوژی بر درمان COVID-19

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. Cover Title Copyright End User License Agreement Contents Foreword Preface List of Contributors COVID -19 Overview Anitha Sriram1, Pravin Medtiya1, Srushti Mahajan1, Rahul Kumar2, Dharmendra Kumar Khatri2, Shashi Bala Singh2, Jitender Madan1 and Pankaj Kumar Singh1,* INTRODUCTION ORIGIN OF SARS-COV-2 RESERVOIR OF SARS-COV-2 GENOME SEQUENCE MAJOR EVENTS IN THE TIMELINE OF THE COVID-19 OUTBREAK REPORTED CONFIRMED CASES, DEATH CASES, AND CASE FATALITY RATE (CFR) OF COVID-19 TYPES OF CORONAVIRUSES AND THEIR OUTBREAK IMPACT Coronavirus Taxonomy of Coronavirus CoronaVirus FACTS OF FATALLY POTENTIAL BETA CORONAVIRUSES CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Virology of SARS-CoV2 Anitha Sriram1, Ravindra Vasave1, Indrani Maji1, Rahul Kumar2, Dharmendra Kumar Khatri2, Shashi Bala Singh2, Neelesh K. Mehra1 and Pankaj Kumar Singh1,* INTRODUCTION DETAILED VIROLOGY OF SARS-COV-2 Size and Content GENOMIC RNA OF SARS-COV-2 NSPs Role in 2019-nCoV Structural Proteins Envelope Protein (E) Membrane Glycoprotein/matrix Glycoprotein (M) Nucleocapsid Protein (N) Spike (S) Protein Two Subunits S1 and S2 of the Spike Protein DETAILED COMPOSITION OF TWO SUBUNITS OF 'S' PROTEIN AND THEIR FUNCTIONS S1 Subunit S2 Subunit COMPONENTS AND FUNCTIONS OF S1 SUBUNIT Components of S1 Subunit BOUNDARY BETWEEN S1 SUBUNIT AND S2 SUBUNIT (S1/S2') FUNCTIONS OF S1 SUBUNITS WHY THE HACE-2 RECEPTOR HAS MORE AFFINITY WITH 2019-NCOV IN COMPARISON TO SARS-COV? STABILIZATION OF VIRUS-BINDING HOTSPOTS ON HACE2 BY 2019-NCOV ROLE OF THIOL-DISULFIDE INTERCHANGES IN THE INTERPLAY BETWEEN 'S' PROTEIN AND HACE2 COMPONENTS AND FUNCTIONS OF S2 SUBUNIT Components of S2 Subunit FP HR1 and HR2 FUNCTIONS OF S2 SUBUNIT SIMILARITY PERCENTAGE (IN TERM OF AMINO ACID SEQUENCE) OF 2019-NCOV WITH THE OTHER COVS CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES SARS-COV-2 Ingress - Triggering COVID-19 Infection Anitha Sriram1, Yojana Bhor1, Srushti Mahajan1, Rahul Kumar2, Saurabh Srivastava1, Dharmendra Kumar Khatri2, Shashi Bala Singh2 and Pankaj Kumar Singh1,* INTRODUCTION ENTRYWAYS OF 2019-NCOV INTO THE HOST CELL Priming of TMPRSS2 Associated Cleavage for the Fusion of Virus Endocytosis Furin Mediated Viral Entry ROLE OF HOST CELL PROTEOLYTIC CLEAVAGE ON ‘S’ PROTEIN OF SARS-COV-2 TMPRSS2 Role for the Fusion of SARS-COV2 Furin Mediated Proteolytic Cleavage at S1/S2 Frontier Other Proteases Involved in the Functioning of Activated Spike Protein WHY VIRAL IMMUNE EVASION IS SEEN IN COVID-19? Pre-fusion and Post-fusion Conformational States of 2019-nCoV Spike Protein Role of SPs, NSPs, and Orfs of 2019-nCoV in Host Immune Evasion (Host IFN Response) Role of Viral VSR (Viral Suppressors of RNA) in Host Immune Evasion HOW ‘S' PROTEIN OF 2019-NCOV IS ACCOUNTABLE FOR VIRUS WIDESPREAD? MUTATIONS OF SARS-COV-2 AND EMERGENCE OF SARS-COV-2 VARIANTS SARS-CoV-2 Variants Alpha Variant Beta Variant Gamma Variant Delta and Kappa Variants A New Variant of SARSCOV2 Called “Omicron” Emerging Genomic Variant Analysis Study Danger Magnitude Levels of Emerging 2019-nCoV Variants CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Epidemiology of COVID-19 Anitha Sriram1, Yojana Bhor1, Srushti Mahajan1, Rahul Kumar2, Saurabh Srivastava1, Dharmendra Kumar Khatri2, Shashi Bala Singh2 and Pankaj Kumar Singh1,* INTRODUCTION LIFE CYCLE OF 2019-NCOV Adsorption Penetration Step Or Fusion Step Uncoating Step Replication Transcription INCUBATION TIME HOW SARS-COV2 SPREADS? Person to Person Airborne Transmission Fecal Contamination Fomite Transmission (Contaminated Objects and Surfaces) Mass Gatherings Mother to the Baby in Pregnancy Condition CLINICAL MANIFESTATIONS OF COVID-19 DISEASE Clinical Symptoms of Mild COVID-19 Disease Symptoms During the Severity of Disease Complications of Very Critically Ill COVID-19 Patients Asymptomatic COVID-19 HIGH RISK OF COVID-19 INFECTION COVID-19 IN CHILDREN CASE FATALITY RATE (CFR IN %) OF COVID-19 Recovery Rate DIAGNOSIS Radiology Findings Laboratory Findings in COVID-19 Serological Findings Immunopathological Findings Mild COVID-19 Infection Severe COVID-19 Infection Hematological Changes Immunological Marker to Assess Severity Autopsy Pathological Findings Pulmonary Findings Blood COVID-19 PREVENTION CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Etiology of COVID-19 Anitha Sriram1, Balram Prajapati1, Srushti Mahajan1, Dharmendra Kumar Khatri2, Shashi Bala Singh2, Saurabh Srivastava1 and Pankaj Kumar Singh1,* INTRODUCTION STAGES OF COVID-19 Healthy Individual STAGES OF COVID-19 INFECTION IN DETAIL Mild COVID-19 Infection: First Stage of Infection Clinical Signs Level of Care Moderate Type of COVID-19 Infection: Second Stage of Infection Host’s Innate Immune System Consequences Lead To The Progression of COVID-19 Host’s Adaptive Immune System Consequences Leading To Progression of COVID-19 Cytotoxic Action of 2019-nCoV on Host Immune Cells Clinical Signs Level of Care Severe Type of COVID-19 Infection: Third Stage of Infection Exuberant Cytokine Storm Enhanced Vascular hyper-Permeability Diffuse Alveolar Damage (DAD) Severe Pneumonia ARDS Acute Lung Injury (ALI) Cause for ALI Complement Activation Disseminated Intravascular Coagulation (DIC) Clinical Signs Level of Care Critically Ill COVID-19 Infection: Fourth Stage of Infection Hyper-inflammation Additionally Causes SIRS SIRS Lead to Septic Shock Multiple Organ Failure (MOF) Acute COVID-19 Cardiovascular Syndrome (ACovCS) Liver Damage Renal Damage Ocular Damage GIT Damage Olfactory Nerve (Brain) Damage ADE (Antibody-Dependent Enhancement) CLINICAL SIGNS LEVEL OF CARE BIOMARKERS IN TESTING COVID-19 SEVERITY Hematological Biomarkers Biochemical Markers Coagulation Biomarkers Inflammatory Biomarkers Potential New Biomarkers CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Damage Response Framework of COVID-19 Anitha Sriram1, Pravin Medtiya1, Srushti Mahajan1, Indrani Maji1, Rahul Kumar2 and Pankaj Kumar Singh1,* INTRODUCTION PATHOGENIC EVENTS DIRECT CYTOTOXIC EFFECT OF 2019-NCOV ON HOST TARGET CELL The Fate of 2019-nCoV and its Interaction with the Host Viral Infection Triggering DOWNREGULATION OF HACE2 AND DYSREGULATION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS) IN HOST BODY When 2019-nCoV Decreases the hACE2 Expression in Lungs and Airways B0AT1 When 2019-nCoV Drops off the hACE2 Expression in the Intestine ENDOTHELIAL CELL DAMAGE AND THROMBOINFLAMMATION DYSREGULATION OF THE IMMUNE RESPONSE CSS Consequences of CSS in COVID-19 Patients ALI ARDS DIC Septic Shock and MOF PROPOSED FACTS BEHIND THE CAUSE OF CSS Reduced hACE2 Maladaptive Host Inflammatory Response Lymphocytopenia Macrophage Activation Syndrome (MAS) Toll-like Receptors (TLRs) Viral Components Inhibition of IFN Signaling by 2019-nCoV High Neutrophil to Lymphocyte Ratios (NLR) Elevated Levels of Extremely pro-inflammatory Th17 Cells That Trigger CSS Role of Interleukins like IL-6 and IL-17 Causing CSS in COVID-19 Patients IL-6 Role IL-17 Role INFLAMMATORY OR IMMUNOLOGICAL MECHANISMS ASSOCIATED WITH COVID-19 DISEASE CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Drug Repurposing Studies in the Progress to Combat COVID-19 Anitha Sriram1, Pravin Medtiya1, Dharmendra Kumar Khatri2, Shashi Bala Singh2, Jitender Madan1 and Pankaj Kumar Singh1,* INTRODUCTION DRUG REPURPOSING SELECTION OF DRUG CANDIDATES FOR DRUG REPURPOSING TO COMBAT COVID-19 PANDEMIC WHO (WORLD HEALTH ORGANIZATION) SOLIDARITY TRIAL Remap-CAP Recovery CURRENT THERAPIES USED IN THE TREATMENT OF COVID-19 PREVENTION OF ATTACHMENT OF VIRUS TO THE TARGET CELL HACE2 Soluble hACE2 Soluble Recombinant Human ACE2 Protein (hrsACE2) Nicotianamine and Glycyrrhizin Dutasteride PREVENTION OF VIRUS FUSION WITH HOST CELL Umifenovir (ArbidolTM) Cathepsin L/B Inhibitor Trypsin Inhibitors TMPRSS2 Protease Inhibitors Camostat Mesylate Nafamostat Mesylate Glecaprevir and Maraviroc PHYTOCHEMICALS THAT MIGHT FIND ACTIVE AGAINST 2019-NCOV Terpenes and Lignans Bromhexine PREVENTION OF VIRAL GENOME REPLICATION RNA Synthesis Inhibitors Ribavirin Remdesivir (RDV) Favipiravir Protease Inhibitors Lopinavir/ritonavir Darunavir Danoprevir Oseltamivir ANTI-MALARIAL THERAPY Chloroquine/Hydroxy Chloroquine (HCQ)/Chloroquine Phosphate (CQP) ANTI-INFLAMMATORY THERAPY Cytokine Storm Syndrome (CSS) Reducing Drugs and Approaches Azithromycin JAK (Janus and kinases) Inhibitors: Both IL-6 and IL-7 Inhibitors IL-6 Pathway Inhibitors Tocilizumab Beta gp130 Fused to the Fc-portion of a Human IgG1 Antibody (sgp130Fc) Protein Ruxolitinib and Baricitnib Sarilumab SERMs (Selective Estrogen Receptor Modulators) Interleukin-17 (IL-17) Inhibitors IL-1 Antagonist IFN-γ Antagonist TNF-α Antagonists Extracorporeal Cytokine Removal Therapy (ECRT) Cytosorb Therapy CELL AND BIOLOGICAL THERAPY Mesenchymal Stem Cells (MSCs) Therapy NK Cells Therapy CORTICOSTEROID THERAPY STATINS THERAPY MULTIPLE DRUG THERAPY ANTICOAGULANTS OTHER DRUGS OR AGENTS THAT MAY BE FOUND TO BE USEFUL FOR THE TREATMENT OF COVID-19 INFECTION Sirolimus Colchicine Ivermectin CRISPR/Cas13d System RLF-100 or Aviptadil TRPV4 Inhibitor Prednisone and HCQ Nanobodies Herbal Agents Nutritional Supplement Niclosamide Nitric Oxide (NO) and Epoprostenol Chlorpromazine (CPZ) Drugs that Suppress TMPRSS2 Gene Expression Ebselen Polypeptide First Nanobody (Nb11-59) via Inhalational Delivery USFDA APPROVED COVID-19 DRUGS CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS BIBLIOGRAPHY Immunotherapeutic Approaches to Combat COVID-19 Anitha Sriram1, Ekta Pardhi1, Indrani Maji1, Rahul Kumar2, Dharmendra Kumar Khatri2, Shashi Bala Singh2, Saurabh Srivastava1 and Pankaj Kumar Singh1,* INTRODUCTION NATURAL IMMUNOMODULATORY APPROACH (IMA) SELECTION OF AN IMMUNOMODULATOR Beta-glucan Therapeutic Applications of 1,3 beta-Glucan and its Role in the Therapy of COVID-19 Macrophage Activation Boosts Innate Immunity Interferon-γ Stimulator Attenuation of CSS Pulmonary Cytoprotection Role of anti-Inflammatory Activity Enhancing IgA Approval of Beta-glucan Dosage Strength of Beta-glucan Chitosan Role of Chitosan as an Anti-Inflammatory Activity The Innate and Adaptive Immune Potentiator Of Chitosan The Expected Outcome from IMA Other Immunomodulators that Might find Potential to Treat COVID-19 Fingolimod Vitamin C (Vit-C) Vitamin D and E Vitamin A (Vit-A) Zinc Supplementation Immunomodulatory Effect Exhibited by Few Drugs IFN THERAPY (ENHANCERS OF ANTIVIRAL IMMUNITY) INTRAVENOUS IMMUNOGLOBULIN (IVIG) CONVALESCENT PLASMA THERAPY (CP) MONOCLONAL ANTIBODIES (MAB) THERAPY Anti-GM-CSF Therapy CR3022 CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Nanotechnology Impact and It’s Future Perspectives on COVID-19 Therapy Anitha Sriram1, Rahul Kumar, Indrani Maji1, Dharmendra Kumar Khatri2, Shashi Bala Singh2, Saurabh Srivastava1 and Pankaj Kumar Singh1,* INTRODUCTION Nanoparticles (NPs) ADVANTAGES OF NANOPARTICLES IN THE COVID-19 DISEASE POLYMERIC NPS MACROPHAGE TARGETING LIGAND COATED PLGA NPS ACTIVE TARGETING MECHANISM OF LIGAND COATED PLGA NANOPARTICLES MIGHT FIND HIGH POTENTIAL TO COMBAT COVID-19 INFECTION IMPACT OF ANTI-VIRAL METALLIC NPS APPROACH NANO VIRICIDES ROLE OF NANOTECHNOLOGY IN EMERGING CORONAVIRUSES INFECTIONS NANOTECHNOLOGY EMERGES AS A BUDDING TOOL IN DIAGNOSING COVID-19 DISEASE Nanohybrids Emerging as Diagnostic Tools in Coronavirus Infections Nanoparticles Emerging as Diagnostic Tools in Coronavirus Infections Lateral Flow Assays of 2019nCoV Field-effect Transistor Nano Biosensor NANO-BASED GENE THERAPY Small Interfering RNAs First Nanobody (Nb11-59) via Inhalational Delivery CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES COVID-19 Vaccines and Vaccination Anitha Sriram1, Mayur Aalhate1, Rahul Kumar2, Dharmendra Kumar Khatri2, Shashi Bala Singh2, Neelesh K. Mehra1 and Pankaj Kumar Singh1 INTRODUCTION VACCINE OPTIONS Antibody Preparation VACCINE STRATEGIES VACCINE DESIGNING APPROACHES Whole Microbe Approach Inactivated Vaccines Examples Live Attenuated Vaccines Examples Viral Vector-based Vaccines Non-Replicating Viral Vector Vaccines Examples Replicating Viral Vector Vaccines Subunit Approach Examples Recombinant Protein-based Approaches Example Newer Nanotechnology Approach: Virus-like Particles (VLPs) Vaccine Genetic Approach RNA-based-vaccines DNA-based Vaccines Examples OTHER TYPES OF VACCINES Might be Next Generation COVID-19 Vaccine Platform-Artificial Antigen-presenting Cells (aAPCs) Vaccines COVID-19a/APC (NCT04299724) WHAT IS THE TARGET ANTIGEN IN COVID-19 VACCINES? THE EUA AUTHORIZED VACCINES The 9 COVID-19 Vaccines Approved by the USFDA for EUA (as of November 2021) The 8 COVID-19 Vaccines approved by the WHO for authorized use or EUA (as of November 2021) COVID-19 VACCINES ROLL OUT TO COMBAT COVID PANDEMIC SITUATION Covaxin Cadila's ZyCoV-D Vaccine Oxford-AstraZeneca OTHER VACCINES THAT ARE ROLLING OUT GLOBALLY Pfizer/BioNTech Sputnik-V Moderna (The mRNA-1273) Vaccine Janssen Vaccine CoronaVac Sinopharm Novavax Repurposed Vaccines under Clinical Trials SIDE EFFECTS OF VACCINES Common Side Effects At the Injection Site of the Human Body Rest of the Human Body FDA Warnings for Both Covishield and Another Oxford AstraZeneca Vaccine FDA Warnings for both Pfizer-BioNTech and Moderna FDA Warnings for Johnson & Johnson’s Vaccine EXPANSION OF BASKET OF COVID-19 VACCINES TO MEET THE GLOBAL SUPPLY- INDISPENSABLE ROLE OF INDIA COMPARISON OF TOPMOST FIVE VACCINES APPROVED BY WHO UNDER EUA A RECENT STUDY PROVES THAT SPUTNIK-V IS THE BEST COVID-19 VACCINE COVID-19 VACCINE IN CHILDREN The Pfizer-BioNTech COVID-19 Vaccine VACCINES EFFICACY AGAINST THE VARIANTS OF CONCERN (VOC) THAT ARE EMERGING DURING THE COVID-19 PANDEMIC Vaccination with Any of the Covid-19 Vaccine as of 21 November 2021 CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Turning Towards Phytopharmaceuticals to Revitalize the Immune System to Fight Against COVID-19 Dharmendra Kumar Khatri1, K Pushpa Tryphena1, Rahul Kumar1, Anitha Sriram2, Pankaj Kumar Singh2, Rupinder Kaur Sodhi3, Jitender Madan1 and Shashi Bala Singh1,* INTRODUCTION SIGNALING NETWORK AND CASCADE OF IMMUNE ARRANGEMENT Immune Response Against Virus Infection Generation of Innate (Non-specific) Immune Response Role of B-cells Mediated Immunity Against SARS-CoV-2 Role of T Cells in an Immune Response against SARS-CoV-2 MOLECULAR TARGET IN SARS-COV-2 FOR IMMUNE RESPONSE CELLULAR ADENOSINE TRIPHOSPHATE: OBLIGATORY FOR INNATE IMMUNITY BOOSTING ATP Promotes the Production of IFN ATP Facilitates IFN Signaling ATP Prevents the Cytokine Storm ATP Thwarts T-cell Apoptosis PHYTOPHARMACEUTICALS AS IMMUNOMODULATORS Withania Somnifera Tinospora Cordifolia Curcuma Longa Glycyrrhiza Glabra Andrographis Paniculata CHALLENGES, OPPORTUNITIES, AND FUTURE PROSPECTS CONCLUSION CLINICAL SIGNIFICANCE CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Subject Index Back Cover