Coronavirus Disease 2019 (COVID-19): Origin, Impact, and Drug Development

At the end of December 2019, in Wuhan, China, a rapidly spreading unknown virus was reported to have caused coronavirus disease of 2019 (COVID-19). Origin linked to Wuhan’s wholesale food market where live animals are sold. This disease is caused by SARS Coronavirus-2 (SARS-CoV-2), which is closely related to the Severe Acute Respiratory Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This virus shares a high sequence identity with bat-derived SARS-like Coronavirus, which indicating its zoonotic origin. The virus spread globally, provoking widespread attention and panic. This Coronavirus is highly pathogenic and causes mild to severe respiratory disorders. Later, it was declared a global pandemic by the World Health Organization (WHO) due to its highly infectious nature and worldwide mortality rate. This virus is a single-stranded, positive-sense RNA genome, and its genome length about 26 to 32 kb that infects a broad range of vertebrates. The researchers worldwide focus on establishing treatment strategies on drug and vaccine development to prevent this COVID-19 pandemic. A drug repurposing approach has been used to identify a rapid treatment for the people affected by COVID-19, which could be cost-effective and bypass some Food and Drug Association (FDA) regulations to move quickly in phase-3 trials. However, there is no promising therapeutic option available yet. This book chapter addresses current information about the COVID-19 disease, including its origins, impacts, and the novel potential drug candidates that can help treat the COVID-19.

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The relevance of dietetic approach of Ayurveda from the perspective of COVID-19 pandemic

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.3077 ◽

2020 ◽

Vol 11 (SPL1) ◽

pp. 748-752

Author(s):

Swapnali Khabade ◽

Bharat Rathi ◽

Renu Rathi

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Healthy Person ◽

World Health ◽

Physical And Mental Health ◽

Leading Role ◽

Global Pandemic ◽

The People ◽

The World ◽

Health Organization ◽

The Individual

A novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes severe acute respiratory syndrome and spread globally from Wuhan, China. In March 2020 the World Health Organization declared the SARS-Cov-2 virus as a COVID- 19, a global pandemic. This pandemic happened to be followed by some restrictions, and specially lockdown playing the leading role for the people to get disassociated with their personal and social schedules. And now the food is the most necessary thing to take care of. It seems the new challenge for the individual is self-isolation to maintain themselves on the health basis and fight against the pandemic situation by boosting their immunity. Food organised by proper diet may maintain the physical and mental health of the individual. Ayurveda aims to promote and preserve the health, strength and the longevity of the healthy person and to cure the disease by properly channelling with and without Ahara. In Ayurveda, diet (Ahara) is considered as one of the critical pillars of life, and Langhana plays an important role too. This article will review the relevance of dietetic approach described in Ayurveda with and without food (Asthavidhi visheshaytana & Lanhgan) during COVID-19 like a pandemic.

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Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic

Frontiers in Pharmacology ◽

10.3389/fphar.2020.578382 ◽

2020 ◽

Vol 11 ◽

Author(s):

Concetta Di Natale ◽

Sara La Manna ◽

Ilaria De Benedictis ◽

Paola Brandi ◽

Daniela Marasco

Keyword(s):

Immune Response ◽

Vaccine Development ◽

Severe Pneumonia ◽

World Health ◽

Primary Host ◽

Viral Pathogen ◽

Drug Candidates ◽

Health Organization ◽

Spread Of Infection

At the end of December 2019, an epidemic form of respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which can cause severe pneumonia and acute respiratory distress syndrome. On January 30, 2020, due to the rapid spread of infection, COVID-19 was declared as a global health emergency by the World Health Organization. Coronaviruses are enveloped RNA viruses belonging to the family of Coronaviridae, which are able to infect birds, humans and other mammals. The majority of human coronavirus infections are mild although already in 2003 and in 2012, the epidemics of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), respectively, were characterized by a high mortality rate. In this regard, many efforts have been made to develop therapeutic strategies against human CoV infections but, unfortunately, drug candidates have shown efficacy only into in vitro studies, limiting their use against COVID-19 infection. Actually, no treatment has been approved in humans against SARS-CoV-2, and therefore there is an urgent need of a suitable vaccine to tackle this health issue. However, the puzzled scenario of biological features of the virus and its interaction with human immune response, represent a challenge for vaccine development. As expected, in hundreds of research laboratories there is a running out of breath to explore different strategies to obtain a safe and quickly spreadable vaccine; and among others, the peptide-based approach represents a turning point as peptides have demonstrated unique features of selectivity and specificity toward specific targets. Peptide-based vaccines imply the identification of different epitopes both on human cells and virus capsid and the design of peptide/peptidomimetics able to counteract the primary host-pathogen interaction, in order to induce a specific host immune response. SARS-CoV-2 immunogenic regions are mainly distributed, as well as for other coronaviruses, across structural areas such as spike, envelope, membrane or nucleocapsid proteins. Herein, we aim to highlight the molecular basis of the infection and recent peptide-based vaccines strategies to fight the COVID-19 pandemic including their delivery systems.

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Main Protease Inhibitors and Drug Surface Hotspot for the Treatment of COVID-19: Drug Repurposing and Molecular Docking Approach

10.26434/chemrxiv.12118857.v1 ◽

2020 ◽

Author(s):

Mahmudul Hasan ◽

Md Sorwer Alam Parvez ◽

Kazi Faizul Azim ◽

Abdus Shukur Imran ◽

Topu Raihan ◽

...

Keyword(s):

Molecular Docking ◽

Drug Repurposing ◽

Pharmacokinetic Parameters ◽

The Novel ◽

Drug Candidates ◽

Target Drug ◽

Global Pandemic ◽

Main Protease ◽

Docking Approach ◽

Repurposed Drugs

<div>The world is facing an unprecedented global pandemic caused by the novel SARS-CoV-2. In the absence</div><div>of a specific therapeutic agent to treat COVID-19 patients, the present study aimed to virtually screen out</div><div>the effective drug candidates from the approved main protease protein (MPP) inhibitors and their</div><div>derivatives for the treatment of SARS-CoV-2. Here, drug repurposing and molecular docking were</div><div>employed to screen approved MPP inhibitors and their derivatives. The approved MPP inhibitors against</div><div>HIV and HCV were prioritized, whilst hydroxychloroquine, favipiravir, remdesivir, and alpha-ketoamide</div><div>were studied as control. The target drug surface hotspot was also investigated through the molecular</div><div>docking technique. ADME analysis was conducted to understand the pharmacokinetics and drug-likeness</div><div>of the screened MPP inhibitors. The result of this study revealed that Paritaprevir (-10.9 kcal/mol), and its</div><div>analog (CID 131982844)(-16.3 kcal/mol) showed better binding affinity than the approved MPP inhibitor</div><div>compared in this study including favipiravir, remdesivir, and alpha-ketoamide. A comparative study among</div><div>the screened putative MPP inhibitors revealed that amino acids T25, T26, H41, M49, L141, N142, G143,</div><div>C145, H164, M165, E166, D187, R188, and Q189 are at critical positions for becoming the surface hotspot</div><div>in the MPP of SARS-CoV-2. The study also suggested that paritaprevir and its' analog (CID 131982844),</div><div>may be effective against SARS-CoV-2 as these molecules had the common drug-surface hotspots on the</div><div>main protease protein of SARS-CoV-2. Other pharmacokinetic parameters also indicate that paritaprevir</div><div>and its top analog (CID 131982844) will be either similar or better-repurposed drugs than already approved</div><div>MPP inhibitors. </div><div><br></div>

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Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments

Frontiers in Immunology ◽

10.3389/fimmu.2021.716407 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sangiliyandi Gurunathan ◽

Min Hee Kang ◽

Jin-Hoi Kim

Keyword(s):

Vaccine Development ◽

Antiviral Drug ◽

Treatment Strategies ◽

Antiviral Drugs ◽

Therapeutic Benefits ◽

Global Pandemic ◽

Lung Injuries ◽

Infected Cells ◽

Intercellular Spread

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized, lipid bilayer-enclosed structures, share structural similarities with viruses secreted from all types of cells, including those lining the respiratory tract. Importantly, the interplay between exosomes and viruses could be potentially exploited for antiviral drug and vaccine development. Exosomes are produced by virus-infected cells and play crucial roles in mediating communication between infected and uninfected cells. SARS-CoV-2 modulates the production and composition of exosomes, and can exploit exosome formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Exosomes have been exploited for therapeutic benefits in patients afflicted with various diseases including COVID-19. Furthermore, the administration of exosomes loaded with immunomodulatory cargo in combination with antiviral drugs represents a novel intervention for the treatment of diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents. Mesenchymal stem cell derived exosomes reduces the cytokine storm and reverse the inhibition of host anti-viral defenses associated with COVID-19 and also enhances mitochondrial function repair lung injuries. We discuss the role of exosomes in relation to transmission, infection, diagnosis, treatment, therapeutics, drug delivery, and vaccines, and present some future perspectives regarding their use for combating COVID-19.

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Biological features of SARS-CoV-2 and current approaches to antiviral therapy and vaccination

Molecular and experimental biology in medicine ◽

10.33602/mebm.3.2.1 ◽

2020 ◽

Vol 3 (2) ◽

pp. 1-16

Author(s):

Snjezana Zidovec Lepej ◽

Dijana Skoric ◽

Petra Simicic ◽

Leona Radmanic ◽

Suzana Harabajsa ◽

...

Keyword(s):

Scientific Community ◽

Vaccine Development ◽

Treatment Strategies ◽

Unknown Origin ◽

Medical Professionals ◽

Immunomodulatory Treatment ◽

International Scientific Community ◽

Biological Features ◽

Global Pandemic

Since the first description of patients with pneumonia of unknown origin in Wuhan in December 2019, unprecedented efforts of the international scientific community led to the identification and molecular characterization of its etiological agent, e.g. SARS-CoV-2. The global pandemic of COVID-19 represents an outstanding challenge for the scientists and medical professionals worldwide. In this review, we discuss the most important aspects of SARS-CoV-2 biology and virology including antiviral and immunomodulatory treatment strategies as well as vaccine development.

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Integrated Docking and Enhanced Sampling Based Selection of Repurposing Drugs for SARS-CoV-2 by Targeting Host Dependent Factors

10.26434/chemrxiv.13369763 ◽

2020 ◽

Author(s):

Amit Kumawat ◽

Sadanandam Namsani ◽

Debabrata Pramanik ◽

Sudip Roy ◽

Jayant K. Singh

Keyword(s):

Regulatory Protein ◽

Drug Repurposing ◽

Md Simulations ◽

Free Energy Calculations ◽

High Throughput Analysis ◽

Drug Candidates ◽

Global Pandemic ◽

Therapeutic Uses ◽

Approved Drugs ◽

Fda Approved Drugs

Since the onset of global pandemic, the most focused research currently in progress is the development of vaccine candidates and clinical trials of existing FDA approved drugs for other relevant diseases, in order to repurpose them for the COVID-19. Here, we investigate the drug repurposing strategies to counteract the coronavirus infection which involves several potential targetable host proteins involved in viral replication and disease progression. We report the high throughput analysis of literature-derived repurposing drug candidates that can be used to target the genetic regulators known to interact with viral proteins based on experimental and interactome studies. In this work we have performed integrated molecular docking followed by molecular dynamics (MD) simulations and free energy calculations through an expedite insilico process where the number of screened candidates reduces sequentially at every step based on physicochemical information. We elucidate that in addition to the pre-clinical and FDA approved drugs that targets specific regulatory proteins, a range of chemical compounds (Nafamostat, Chloramphenicol, Ponatinib) binds to the other gene transcription and translation regulatory protein with higher affinity and may harbour potential for therapeutic uses.<br>

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Insights into the Severe Acute Respiratory Syndrome Coronavirus-2: Transmission, Genome Composition, Replication, Diagnostics and Therapeutics

Current Journal of Applied Science and Technology ◽

10.9734/cjast/2020/v39i2130825 ◽

2020 ◽

pp. 71-91

Author(s):

Rubi Gupta ◽

Ricky Raj Paswan ◽

Richita Saikia ◽

Basanta Kumar Borah

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Vaccine Development ◽

Drug Repurposing ◽

Scientific Basis ◽

World Health ◽

Viral Receptor ◽

Angiotensin Converting Enzyme 2 ◽

Therapeutic Development ◽

Private Sector Organizations ◽

Health Organization

The Severe Acute Respiratory Syndrome Coronavirus-2, originated in Wuhan, China in late 2019 has created a massive pandemic; the disease manifested by the virus was named as COVID-19 by World Health Organization. It has appeared as an unprecedented threat against the global health scenario, as well as the world socio-economic-political structure. The infection of the plausibly animate-origin virus, per se, is not dangerous; but its extremely contagious and infectious nature is the major challenge it has posed. In human, the viral receptor is angiotensin converting enzyme-2, which is present in the cellular membranes of multiple vital organs. The virus has different longevity in different contaminated surfaces which are the principal modes of its transmission. No immunity has so far been reported against the virus; however, immuno-compromised individuals are more vulnerable. For its diagnosis, mainly reverse transcription-based diagnosis is presently being used; however, serological diagnosis is still not a regular practice due to several reasons. Multiple public as well as private sector organizations are working towards vaccine development; research for antiviral drugs and drug-repurposing is also in progress. Several candidate vaccines and drugs are now in various levels of clinical trials. Here, we summarize the scientific basis of the pandemic; its diagnosis, treatment and efforts towards therapeutic development. These efforts will prove useful against future emerging and re-emerging human and non-human epidemics as well as pandemics.

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COVID-19: Characteristics and Therapeutics

Cells ◽

10.3390/cells10020206 ◽

2021 ◽

Vol 10 (2) ◽

pp. 206 ◽

Cited By ~ 1

Author(s):

Rameswari Chilamakuri ◽

Saurabh Agarwal

Keyword(s):

Molecular Mechanisms ◽

Vaccine Development ◽

Clinical Manifestations ◽

Treatment Strategies ◽

Drug Repurposing ◽

World Health ◽

Pharmacological Intervention ◽

Multiple Treatment ◽

The Usa ◽

Novel Coronavirus

Novel coronavirus (COVID-19 or 2019-nCoV or SARS-CoV-2), which suddenly emerged in December 2019 is still haunting the entire human race and has affected not only the healthcare system but also the global socioeconomic balances. COVID-19 was quickly designated as a global pandemic by the World Health Organization as there have been about 98.0 million confirmed cases and about 2.0 million confirmed deaths, as of January 2021. Although, our understanding of COVID-19 has significantly increased since its outbreak, and multiple treatment approaches and pharmacological interventions have been tested or are currently under development to mitigate its risk-factors. Recently, some vaccine candidates showed around 95% clinical efficacy, and now receiving emergency use approvals in different countries. US FDA recently approved BNT162 and mRNA-1273 vaccines developed by Pfizer/BioNTech and Moderna Inc. for emergency use and vaccination in the USA. In this review, we present a succinct overview of the SARS-CoV-2 virus structure, molecular mechanisms of infection, COVID-19 epidemiology, diagnosis, and clinical manifestations. We also systematize different treatment strategies and clinical trials initiated after the pandemic outbreak, based on viral infection and replication mechanisms. Additionally, we reviewed the novel pharmacological intervention approaches and vaccine development strategies against COVID-19. We speculate that the current pandemic emergency will trigger detailed studies of coronaviruses, their mechanism of infection, development of systematic drug repurposing approaches, and novel drug discoveries for current and future pandemic outbreaks.

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A Comprehensive Overview On The Most Recent Trends In Covid-19 Diagnosis, Treatment Options And Vaccine Development Status

10.53049/tjopam.2021.v001i01.001 ◽

2021 ◽

Vol 001 (01) ◽

Author(s):

Jayendrakumar Patel ◽

Shalin Parikh ◽

Shwetaben Patel

Keyword(s):

Vaccine Development ◽

Treatment Options ◽

Supportive Therapy ◽

Cost Effective ◽

The Novel ◽

Comprehensive Overview ◽

Development Status ◽

Global Pandemic ◽

Recent Trends ◽

Antiviral Medications

The global pandemic produced by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first appeared in Wuhan, China, in December 2019 and which then spread rapidly, made it difficult to find or develop effective medications for its prevention and treatment. Therefore, the first stage is necessitating the use of a precise and quick diagnostic method to detect SARS-CoV-2 infected patient followed by effective patient isolation and the commencement of early treatment, which can range from supportive therapy to specialised medications such corticosteroids, antiviral medications, antibiotics, and the recently introduced convalescent plasma. Despite the extraordinary developments in advanced medicinal system, no confirmed viable medicines exist at this time. Rapid research on SARS CoV-2 epidemiology has led to the discovery of certain new targets for prospective therapeutic treatments. Many therapeutic options have been evaluated, and clinical studies are proceeding at a breakneck speed. However, there is a lot of room for more study into finding cost-effective and safer medicines, vaccinations, and measures to ensuring that COVID-19 preventive and treatment programmes are available to everyone. The goal of this study is to compile all of the current advancements in the worldwide medical system in the fight against COVID-19.

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