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.

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 DRUG REPURPOSING FOR MALARIA AND DENGUE USING COMPUTATIONAL MODELLING.

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Prajakta Velankar ◽  
Sara Rehman ◽  
Yukti Thakkar
Keyword(s):  
Clinical Trials ◽  
Drug Design ◽  
Antiviral Activity ◽  
Computational Modelling ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
Quantum Mechanical ◽  
Rational Drug ◽  
The World ◽  
Approved Drugs

By and by the world is in a battle with the diseases like Malaria and Dengue with no prompt medicines accessible the scourge brought about by the Malaria and Dengue is expanding step by step. A ton of researchers are continuing for the potential medication up-and-comer that could help the medical care framework in this battle. We present a docking?based screening using a quantum mechanical scoring of a library built from approved drugs ie Remdesivir, Hydroxy-chloroquine, Curcumin, Moroxydine, Artesunate Sulphate, Mefloquine, Doxycycline, Atovaquone, Indinavir, and compounds that are with Malaria and Dengue Mpro Proteins could display antiviral activity against these diseases. 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 Malaria and Dengue Keywords: Malaria, Dengue, Drug Repurposings, Computer Aid Drug Design, In silico drug development

scholarly journals Drug Repurposing: In Silico Modeling of Mucor Mycosis

2021 ◽  
pp. 53-61
Author(s):  
Bharat Kwatra ◽  
Barshana Bhattacharya ◽  
Tanvi Khokhawat ◽  
Aaron Raphael Jes ◽  
Monish Bhati ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antifungal Activity ◽  
Benzoic Acid ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
Quantum Mechanical ◽  
Medical Care System ◽  
Rational Drug ◽  
In Silico Modeling ◽  
Approved Drugs

The globe has recently been fighting a battle with black fungus, also known as Mucormycosis, and with no immediate treatments available, the disease's devastation is spreading at an alarming rate. A large number of researchers are still looking for a promising new drug that could aid the medical care system in this fight. A docking-based screening employing quantum mechanical scoring of a library is shown, built from approved drugs and compounds that Ellagic acid, Hesperetin, Capsaicin, Concanavalin, Cinnamic acid, Quercetin, Citronellal, Limonene, Progoitrin, Sinigrin, Allicin, Curcumin, Indole, Resveratrol, Strigol, D-limonene, Benzoic acid, Panaxydol, Kaempferol and Berberine with Protein with PDB id 6VCT could display antifungal activity against Mucormycosis. 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 Mucormycosis.

scholarly journals An evidence-based systematic review on emerging therapeutic and preventive strategies to treat novel coronavirus (SARS-CoV-2) during an outbreak scenario

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anupama M. Gudadappanavar ◽  
Jyoti Benni
Keyword(s):  
Antiviral Drug ◽  
Drug Repurposing ◽  
Respiratory Illness ◽  
World Health ◽  
Recombinant Vaccines ◽  
Subunit Vaccines ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Full Length Genome

AbstractA novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.

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.

An Overview of the Treatment Contributions Measured Globally for COVID19 Outbreak

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Sheikh Saba Naz ◽  
Iqra Munir
Keyword(s):  
Clinical Trials ◽  
Transmission Rate ◽  
Antiviral Drug ◽  
Respiratory Illness ◽  
World Health ◽  
Pubmed Central ◽  
Genomic Studies ◽  
Extensive Information ◽  
Health Organization ◽  
Specific Antiviral Therapy

Background: SARS CoV2 is a newly emerged animal beta coronavirus that causes respiratory illness. This infection has affected 212 countries to date and has been declared a pandemic by the World Health Organization. Due to the high transmission rate and lack of availability of any approved antiviral drug, the formulation of a specific antiviral therapy has now become a global emergency. Genomic studies have revealed 79% identity of SARS CoV2 with SARS CoV and 50% identity with MERS CoV, which has given a clue point to test the drugs that were efficient against previously encountered beta coronaviruses. For this purpose, several clinical trials based on the knowledge of existing drugs are moving ahead. These therapies include chloroquine and hydroxychloroquine, remdesivir, corticosteroids therapy, favipiravir, ribavirin, lopinavir/ritonavir, anti-cytokine therapy, and convalescent sera. Aim of the study: The purpose of this review is to give a pointer of contributions conducted globally including strategies utilized for treatments, the pattern of dosage, adverse reactions, and effective outcomes from different drugs. Methodology: Literature has been retrieved from PubMed, PubMed Central, ResearchGate, ScienceDirect, and Google Scholar, using a combination of keywords for extensive information. Conclusion: Among all the drug options, Remdesivir and the use of Convalescent Sera have been considered as the safest option for treatment against COVID19. Data from the ongoing clinical trials will be required for the formulation of a specific and approved antiviral drug.

scholarly journals FDA Approved Drugs and Herbal Based Inhibitors Target SARS CoV-2 RNA Dependent RNA Polymerase

2021 ◽  
Vol 11 (3) ◽  
pp. 3811-3821
Keyword(s):  
Rna Polymerase ◽  
Drug Repurposing ◽  
World Health ◽  
In Vivo Studies ◽  
Rna Dependent Rna Polymerase ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Approved Drugs

The recent outburst of COVID-19 started as an epidemic in Wuhan city, China, in December 2019. It was declared a pandemic by World Health Organization on 30 January 2020. The rapid spread of the novel coronavirus leads to more deaths worldwide. Also, it has spared many lives in its second wave of disease in many countries. Although scientists had produced vaccines, it does not suit every human being, and they are getting infected again, which is due to a lack of extensive clinical trials. Also, drug repurposing is ineffective. There is a need for more research; using in silico methods may be the better option in the current situation to save the lives of virus-affected individuals. The drugs used for other diseases and herbal compounds might help target the coronavirus. In this study, a protein, RNA-dependent RNA polymerase (RdRp), was chosen as a target from the virus for molecular docking. It was docked against several drugs on the market and also several herbal compounds. This study will help further in vitro and in vivo studies with new lead compounds, new horizons for drugs in trials, and a new approach for Insilco analysis to treat COVID-19.

Outbreak of coronavirus disease 2019 (COVID-19) and its manifestation

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Bikash Debnath ◽  
Waikhom Somraj Singh ◽  
Kuntal Manna
Keyword(s):  
Antiviral Drug ◽  
World Health ◽  
Family Welfare ◽  
Pregnant Mother ◽  
Vaccine Candidates ◽  
The World ◽  
Mode Of Transmission ◽  
Health Organization ◽  
Effective Drugs ◽  
Respiratory Droplets

: The coronavirus disease 2019 (COVID-19) first outbreak in Wuhan, China, and the infection is intense worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for COVID-19. The World Health Organization (WHO) confirmed total deaths had noted 4.20% globally (March 21, 2020). Between the intervals of four months (July 21, 2020), confirmed total deaths had recorded 4.17%, globally. In India, 909 confirmed cases and 19 deaths were reported by Health and Family Welfare, Government of India, March 28, 2020. Between the intervals of 123 days In India, 1638870 confirmed cases and 35684 deaths. COVID-19 can potentially spread from person to person through direct contact or respiratory droplets from coughing and sneezing. The most common symptoms are fever, dry cough, difficulty in breathing, and fatigue. A pregnant mother with COVID-19 has fewer chances to transfer this infection of her newborn babies. Children have less affected than an adult. A specific antiviral drug or vaccine has not been developed to cure the disease. Chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, nitazoxanide, and remdesivir have effective drugs to treat COVID-19. Many vaccine candidates are under pre-clinical and clinical studies. In this review, we highlight the epidemiology, sign-symptoms, pathogenesis, mode of transmission, and effects of a pregnant mother with newborns, children, prevention, and drugs affective to COVID-19.

Reflections on FDA and WHO recommendations concerning clinical trials

1989 ◽  
Vol 4 (2) ◽  
pp. 117-122 ◽  
Author(s):  
J.-F. Dreyfus ◽  
D. Cremniter ◽  
J.D. Guelfi
Keyword(s):  
Clinical Trials ◽  
Drug Users ◽  
Objective Evaluation ◽  
World Health ◽  
Measuring Instruments ◽  
New Techniques ◽  
The Usa ◽  
The One ◽  
Health Organization

SummaryWe are still confronted by numerous different nosographic models and problems concerning the objective evaluation of patients progress during treatment. It is interesting to consider the consequences of this situation in psychiatry which still involves a relative diversity of practical methods used in clinical trials. The recommendations of the USA Food and Drug Administration, on the one hand, constitute a highly structured and precise reference. The World Health Organization, on the other hand, promulgates general recommendations resulting from a compromise designed to satisfy the greatest number of clinicians.Despite the apparently diverse principles and the different practical methods they propose, both those sets of recommendations have been useful in inspiring clinicians to reflect upon these different methodological approaches. The qualities of the inclusion criteria used in the study of patients and the sensitivity of the different measuring instruments have allowed psychotropic drug users as well as producers to recognize the need for a certain rigour in clinical trials.The FDA and WHO guidelines have certainly improved the quality of clinical trials in psychopharmacology. However, they also represent a source of resistance to innovation.A series of consensus meetings to first reconcile US and European points of view and later to include new techniques in the recognized sets of methods would therefore be helpful.

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