Therapeutic Targets and Computational Approaches on Drug Development for COVID-19

2020 ◽  
Vol 20 (24) ◽  
pp. 2210-2220 ◽  
Author(s):  
Anusuya Shanmugam ◽  
Nisha Muralidharan ◽  
Devadasan Velmurugan ◽  
M. Michael Gromiha
Keyword(s):  
Drug Development ◽  
Computational Methods ◽  
Drug Repurposing ◽  
World Health ◽  
Short Peptides ◽  
Computational Approaches ◽  
Lead Compounds ◽  
The World ◽  
Health Organization ◽  
Approved Drugs

World Health Organization declared coronavirus disease (COVID-19) caused by SARS coronavirus-2 (SARS-CoV-2) as pandemic. Its outbreak started in China in Dec 2019 and rapidly spread all over the world. SARS-CoV-2 has infected more than 800,000 people and caused about 35,000 deaths so far, moreover, no approved drugs are available to treat COVID-19. Several investigations have been carried out to identify potent drugs for COVID-19 based on drug repurposing, potential novel compounds from ligand libraries, natural products, short peptides, and RNAseq analysis. This review is focused on three different aspects; (i) targets for drug design (ii) computational methods to identify lead compounds and (iii) drugs for COVID-19. It also covers the latest literature on various hit molecules proposed by computational methods and experimental techniques.

scholarly journals COVID-19 Drug Discovery Using Intensive Approaches

2020 ◽  
Vol 21 (8) ◽  
pp. 2839 ◽  
Author(s):  
Ayumu Asai ◽  
Masamitsu Konno ◽  
Miyuki Ozaki ◽  
Chihiro Otsuka ◽  
Andrea Vecchione ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Viruses ◽  
Drug Repurposing ◽  
Global Scale ◽  
Therapeutic Agents ◽  
Clinical Development ◽  
World Health ◽  
Antiviral Therapies ◽  
The World ◽  
Health Organization

Since the infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China during December 2019, the coronavirus disease 2019 (COVID-19) has spread on a global scale, causing the World Health Organization (WHO) to issue a warning. While novel vaccines and drugs that target SARS-CoV-2 are under development, this review provides information on therapeutics which are under clinical trials or are proposed to antagonize SARS-CoV-2. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), drug repurposing might be a viable strategy. Since several antiviral therapies can inhibit viral replication cycles or relieve symptoms, mechanisms unique to RNA viruses will be important for the clinical development of antivirals against SARS-CoV-2. Given that several currently marketed drugs may be efficient therapeutic agents for severe COVID-19 cases, they may be beneficial for future viral pandemics and other infections caused by RNA viruses when standard treatments are unavailable.

scholarly journals Insights on Epidemiology, Pathogenesis, Diagnosis and Possible Treatment of COVID-19 infection

2020 ◽  
Author(s):  
SHASHANK KUMAR MAURYA ◽  
Amit Bhattacharya ◽  
Pooja Shukla ◽  
RAJNIKANT MISHRA
Keyword(s):  
Drug Repurposing ◽  
Review Article ◽  
World Health ◽  
Specific Drug ◽  
Clinical Practices ◽  
Indian Government ◽  
The World ◽  
Health Organization ◽  
And Control ◽  
Primary Transmission

COVID-19, SARS-CoV-2 virus of the coronavirus family, created worldwide infectious outbreak affecting millions of people across the globe showing mild to severe symptoms of pneumonia and acute respiratory distress. Absence of precise information on primary transmission, diagnosis, prognosis, and therapeutics for patients with COVID-19 makes prevention and control tough. Treatment of millions of COVID19 patients without any specific drug is one of the biggest challenge, many existing antiviral drugs are in use as an alternative treatment and hunting is still on the way to develop COVID19 specific drug and vaccine. Being the world second largest populated country, fluctuating climatic condition at every 4 months, India is also at the high risk for spread of COVID19 infection. This review article has been intended to discuss biology of COVID-19, mechanism of COVID-19 infection in humans, epidemiology, possible effect of COVID19 infection on pregnancy, nervous system, individuals diabetes and cardiovascular disease, drug repurposing strategy as an alternative line of treatment and clinical practices recommended by World Health Organization (WHO) and other government agencies followed by situation and measures taken by Indian government to minimize the spread of COVID19 in India.

scholarly journals Tackling the COVID-19 Pandemic- A Review

2021 ◽  
Vol 29 (2) ◽  
pp. 175-186
Author(s):  
CC Nganwuchu ◽  
K Habas ◽  
N Mohammed ◽  
M Osei Wusuansa ◽  
D Makanjuola ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Health Impact ◽  
Diagnostic Methods ◽  
World Health ◽  
Personal Hygiene ◽  
Diagnostic Tools ◽  
Wide Range ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

Since December 2019, a new type of coronavirus called novel coronavirus (2019-nCoV, or COVID-19) was identified in Wuhan, China and on March 11, 2020, the World Health Organization (WHO) has declared the novel coronavirus (COVID-19) outbreak a global pandemic. With more than 101,797,158 confirmed cases, resulting in 3,451,354 deaths as of May 21, 2021, the world faces an unprecedented economic, social, and health impact. The clinical spectrum of COVID-19 has a wide range of manifestations, ranging from an asymptomatic state or mild respiratory symptoms to severe viral pneumonia and acute respiratory distress syndrome. Several diagnostic methods are currently available for detecting the coronavirus in clinical, research, and public health laboratories. Some tests detect the infection directly by detecting the viral RNA using real time reverse transcriptase polymerase chain reaction (RT-PCR) and other tests detect the infection indirectly by detecting the host antibodies. Additional techniques are using medical imaging diagnostic tools such as X-ray and computed tomography (CT). Various approaches have been employed in the development of COVID-19 therapies. Some of these approaches use drug repurposing (e.g. Remdesivir and Dexamethasone) and combinational therapy (e.g. Lopinavir/Ritonavir), whilst others aim to develop anti-viral vaccines (e.g. mRNA and antibody). Additionally, health experts integrate data sharing, provide with guidelines and advice to minimize the effects of the pandemic. These guidelines include wearing masks, avoiding direct contact with infectious people, respiratory and personal hygiene. Taken together, an extensive knowledge on transmission mechanisms, clinical spectrums, specific diagnostics methods, host-virus interactions are required to tackle this pandemic. J. Bio-Sci. 29(2): 175-186, 2021 (December)

scholarly journals In silico Drug Repurposing for COVID-19: Targeting SARS-CoV-2 Proteins through Docking and Quantum Mechanical Scoring

2020 ◽  
Author(s):  
Claudio Cavasotto ◽  
Juan Di Filippo
Keyword(s):  
Clinical Trials ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
World Health ◽  
Quantum Mechanical ◽  
S Protein ◽  
Compound Screening ◽  
Health Organization ◽  
Approved Drugs

In December 2019, an infectious disease caused by the coronavirus SARS-CoV-2 appeared in Wuhan, China. This disease (COVID-19) spread rapidly worldwide, and on March 2020 was declared a pandemic by the World Health Organization (WHO). Today, almost 1,5 million people have been infected, with more than 85,000 casualties. Today, no vaccine nor antiviral drug is available. While the development of a vaccine might take at least a year, and for a novel drug, even longer; finding a new use to an old drug (drug repurposing) could be the most effective strategy. We present a docking-based screening using a quantum mechanical scoring of a library built from approved drugs and compounds undergoing clinical trials, against three SARS-CoV-2 target proteins: the spike or S-protein, and two proteases, the main protease and the papain-like<br>protease. The S-protein binds directly to the Angiotensin Converting Enzyme 2 receptor of the human host cell surface, while the two proteases process viral polyproteins.<br>Following the anaylysis of our structure-based compound screening, we propose several structurally diverse compounds (either FDA-approved or in clinical trials) that could display antiviral activity against SARS-CoV-2. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the disease. We hope that these findings may contribute to the rational drug design against COVID-19.

scholarly journals In silico Drug Repurposing for COVID-19: Targeting SARS-CoV-2 Proteins through Docking and Quantum Mechanical Scoring

2020 ◽  
Author(s):  
Claudio Cavasotto ◽  
Juan Di Filippo
Keyword(s):  
Clinical Trials ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
World Health ◽  
Quantum Mechanical ◽  
Chemical Library ◽  
S Protein ◽  
Health Organization ◽  
Approved Drugs

In December 2019, an infectious disease caused by the coronavirus SARS-CoV-2 appeared in Wuhan, China. This disease (COVID-19) spread rapidly worldwide, and on March 2020 was declared a pandemic by the World Health Organization (WHO). Today, more than 4.7 million people have been infected, with almost 320,000 casualties, while no vaccine nor antiviral drug is in sight. The development of a vaccine might take at least a year, and even longer for a novel drug; thus, finding a new use to an old drug (drug repurposing) could be the most effective strategy. We present a high-throughput docking approach using a novel quantum mechanical scoring for screening a chemical library of ~11,500 molecules built from FDA-approved drugs and compounds undergoing clinical trials, against three SARS-CoV-2 target proteins: the spike or S-protein, and two proteases, the main protease and the papain-like protease. The S-protein binds directly to the Angiotensin Converting Enzyme 2 receptor of the human host cell surface, while the two proteases process viral polyproteins. Following the analysis of our structure-based virtual screening, we propose several structurally diverse compounds that could display antiviral activity against SARS-CoV-2. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the disease. We hope that these findings may contribute to the rational drug design against COVID-19.

The outbreak of Novel Coronavirus a New Type of Threat in 2020: Genesis, Detection, Treatment, and Management

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Dinesh Mohan S ◽  
Santhosha D ◽  
Gupta VRM ◽  
Mrunalini S
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Primary Source ◽  
World Health ◽  
London School ◽  
Live Animal ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Approved Drugs

Background: COVID-19 is a new, health-threatening infectious disease in the world in 2020, caused novel coronavirus SARS-CoV-2. As of July 13, 2020, 4,881,579 active cases of COVID-19 have been diagnosed and 571,080 deaths globally. In India, 301,850 active cases and 23,187 deaths have been reported. To date, there is no effective treatment made available against the deadly virus SARS-CoV-2. The drug manufacturers, institutional laboratories, and other organizations start developing vaccines to combat the COVID-19 infection. Methods: Science Direct, Elsevier, Pub med, Scopus, and Nature databases were referred to know the current scenario of disease. Moreover, the recent data has also been obtained from the World Health Organization (WHO), Centre of Disease Control (CDCs), case studies, newspaper, and worldometer reports. Vaccine Centre at the London School of Hygiene & Tropical Medicine, Clinicaltrials.gov, US National Library of Medicine, has also been accessed to get the latest information about ongoing clinical trials. Result: The primary source of the SARS-CoV-2 outbreak is connected to the Hunan seafood and live animal market in Wuhan city, Hubei Province, China. Like; SARS-CoV, and MERS-CoV, SARS-CoV-2 is also a zoonotic virus affecting the lower respiratory tract in humans. The pathogenesis of COVID-19 involves attachment of its Spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor in the lower respiratory tract in humans. The most common symptoms of COVID-19 are fever, cough, sore throat, fatigue, headache, myalgia, septic shock, and breathlessness. Few patients with COVID-19 infection experience diarrhea, vomiting, and abdominal pain. Currently, FDA approved drugs being used to treat COVID-19. Conclusion: This review article presents the importance of traditional Indian herbs recommended by AYUSH as precautionary and curative measures of COVID-19 until vaccines and drugs are made available. Moreover, this article discussed the origin, symptoms, mode of transmission, management, and diagnostics techniques for the detection of the SARS-CoV-2 virus.

scholarly journals Alternatives to Remdesivir: Drug repurposing for inhibition of SARSCoV2 RNA dependent RNA polymerase

2021 ◽  
Author(s):  
Kumar Sharp
Keyword(s):  
New England ◽  
Herd Immunity ◽  
Specific Treatment ◽  
Drug Repurposing ◽  
Clinical Results ◽  
World Health ◽  
Large Set ◽  
Rna Dependent Rna Polymerase ◽  
The World ◽  
Health Organization

Abstract Even after more than a year of the beginning of COVID-19 pandemic, a specific treatment for the disease has not been discovered. Vaccination programmes are being rolled out as the fastest pace possible but achievement of herd immunity will take time.[1] Many drugs like favipiravir, remdesivir and tocilizumab are being used for the treatment of this disease but reports published by the World Health Organization and the New England Journal of Medicine shows that they do not produce any significant clinical results. In this study, by molecular docking a large set of drugs has been used to replace remdesivir in RdRp protein so that they can produce the same action and therefore provide suitable alternatives for clinical trials and emergency use. The drugs identified in the study are saquinavir, cefoperazone, gliquidone, nelfinavir, 5-methyltetrahyrofolate among various others.

scholarly journals In silico Drug Repurposing for COVID-19: Targeting SARS-CoV-2 Proteins through Docking and Quantum Mechanical Scoring

2020 ◽  
Author(s):  
Claudio Cavasotto ◽  
Juan Di Filippo
Keyword(s):  
Clinical Trials ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
World Health ◽  
Quantum Mechanical ◽  
Chemical Library ◽  
S Protein ◽  
Health Organization ◽  
Approved Drugs

In December 2019, an infectious disease caused by the coronavirus SARS-CoV-2 appeared in Wuhan, China. This disease (COVID-19) spread rapidly worldwide, and on March 2020 was declared a pandemic by the World Health Organization (WHO). Today, more than 4.7 million people have been infected, with almost 320,000 casualties, while no vaccine nor antiviral drug is in sight. The development of a vaccine might take at least a year, and even longer for a novel drug; thus, finding a new use to an old drug (drug repurposing) could be the most effective strategy. We present a high-throughput docking approach using a novel quantum mechanical scoring for screening a chemical library of ~11,500 molecules built from FDA-approved drugs and compounds undergoing clinical trials, against three SARS-CoV-2 target proteins: the spike or S-protein, and two proteases, the main protease and the papain-like protease. The S-protein binds directly to the Angiotensin Converting Enzyme 2 receptor of the human host cell surface, while the two proteases process viral polyproteins. Following the analysis of our structure-based virtual screening, we propose several structurally diverse compounds that could display antiviral activity against SARS-CoV-2. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the disease. We hope that these findings may contribute to the rational drug design against COVID-19.

scholarly journals Potential Repurposed Therapeutics and New Vaccines against COVID-19 and Their Clinical Status

2020 ◽  
Vol 25 (10) ◽  
pp. 1097-1107
Author(s):  
Abid H. Banday ◽  
Shameem A. Shameem ◽  
Sheikh J. Ajaz
Keyword(s):  
Clinical Status ◽  
Clinical Information ◽  
The United States ◽  
World Health ◽  
Governmental Organizations ◽  
Investigational Drugs ◽  
The World ◽  
Health Organization ◽  
Approved Drugs ◽  
Almost All

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first reported in Wuhan, China, in December 2019. Since then, the virus has stretched its grip to almost all the countries in the world, affecting millions of people and causing enormous casualties. The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2019. As of June 12, 2020, almost 7.30 million people have already been infected globally, with 413,000 reported casualties. In the United States alone, 2.06 million people have been infected and 115,000 have succumbed to this pandemic. A multipronged approach has been launched toward combating this pandemic, with the main focus on exhaustive screening, developing efficacious therapies, and vaccines for long-term immunity. Several pharmaceutical companies in collaboration with various academic institutions and governmental organizations have started investigating new therapeutics and repurposing approved drugs so as to find fast and affordable treatments against this disease. The present communication is aimed at highlighting the efforts that are currently underway to treat or prevent SARS-CoV-2 infection, with details on the science, clinical status, and timeline for selected investigational drugs and vaccines. This article is going to be of immense help to the scientific community and researchers as it brings forth all the necessary clinical information of the most-talked-about therapeutics against SARS-CoV-2. All the details pertaining to the clinical status of each therapeutic candidate have been updated as of June 12, 2020.

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