scholarly journals Repurposing the Natural Compound for Antiviral During an Epidemic -a Case Study on the Drug Repurpose of Natural Compounds to Treat COVID-19

2020 ◽  
Author(s):  
Zhihao Wang ◽  
Chi Xu ◽  
Bing Liu ◽  
Nan Qiao
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Natural Compound ◽  
Early Stage ◽  
Drug Repurposing ◽  
The United States ◽  
Natural Compounds ◽  
Global Scale ◽  
Novel Coronavirus ◽  
Approved Drugs

<p>The pandemic caused by the novel coronavirus SARS-CoV-2 is rapidly spreading and infecting the population on the global scale, it is a global health threat due to its high infection rate, high mortality and the lack of clinically approved drugs and vaccines for treating the disease (COVID-19). Utilising the published structures and homologue remodelling for proteins from SARS-CoV-2, an <i>in silico</i> molecular docking based screening was conducted and deposited in the Shennong project database. The results from the screening could be used to explain the clinical observation of repurposing the Ritonavir and Lopinavir to treat patients in the early stage of COVID-19 infection, and the prescription of Remdisivir in the United States as the therapy. Additionally, this molecular docking identified natural compound candidates for drug repurposing. This <i>in silico </i>molecular docking screen may be used for the initatial evaluation and rationalisation for drug repurposing of other potential candidates, especially other natural compounds from traditional Chinese medicines.</p>

scholarly journals Repurposing the Natural Compound for Antiviral During an Epidemic -a Case Study on the Drug Repurpose of Natural Compounds to Treat COVID-19

2020 ◽  
Author(s):  
Zhihao Wang ◽  
Chi Xu ◽  
Bing Liu ◽  
Nan Qiao
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Natural Compound ◽  
Early Stage ◽  
Drug Repurposing ◽  
The United States ◽  
Natural Compounds ◽  
Global Scale ◽  
Novel Coronavirus ◽  
Approved Drugs

<p>The pandemic caused by the novel coronavirus SARS-CoV-2 is rapidly spreading and infecting the population on the global scale, it is a global health threat due to its high infection rate, high mortality and the lack of clinically approved drugs and vaccines for treating the disease (COVID-19). Utilising the published structures and homologue remodelling for proteins from SARS-CoV-2, an <i>in silico</i> molecular docking based screening was conducted and deposited in the Shennong project database. The results from the screening could be used to explain the clinical observation of repurposing the Ritonavir and Lopinavir to treat patients in the early stage of COVID-19 infection, and the prescription of Remdisivir in the United States as the therapy. Additionally, this molecular docking identified natural compound candidates for drug repurposing. This <i>in silico </i>molecular docking screen may be used for the initatial evaluation and rationalisation for drug repurposing of other potential candidates, especially other natural compounds from traditional Chinese medicines.</p>

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Potential 2019-nCoV 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches

2020 ◽  
Author(s):  
Alex Zhavoronkov ◽  
Vladimir Aladinskiy ◽  
Alexander Zhebrak ◽  
Bogdan Zagribelnyy ◽  
Victor Terentiev ◽  
...  
Keyword(s):  
Homology Modelling ◽  
Drug Repurposing ◽  
Hiv Protease ◽  
Learning Approaches ◽  
Protein Targets ◽  
Chemical Libraries ◽  
Internal Resources ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Novel Drug

<div> <div> <div> <p>The emergence of the 2019 novel coronavirus (2019-nCoV), for which there is no vaccine or any known effective treatment created a sense of urgency for novel drug discovery approaches. One of the most important 2019-nCoV protein targets is the 3C-like protease for which the crystal structure is known. Most of the immediate efforts are focused on drug repurposing of known clinically-approved drugs and virtual screening for the molecules available from chemical libraries that may not work well. For example, the IC50 of lopinavir, an HIV protease inhibitor, against the 3C-like protease is approximately 50 micromolar. In an attempt to address this challenge, on January 28th, 2020 Insilico Medicine decided to utilize a part of its generative chemistry pipeline to design novel drug-like inhibitors of 2019-nCoV and started generation on January 30th. It utilized three of its previously validated generative chemistry approaches: crystal-derived pocked- based generator, homology modelling-based generation, and ligand-based generation. Novel druglike compounds generated using these approaches are being published at www.insilico.com/ncov-sprint/ and will be continuously updated. Several molecules will be synthesized and tested using the internal resources; however, the team is seeking collaborations to synthesize, test, and, if needed, optimize the published molecules. </p> </div> </div> </div>

scholarly journals Indicator Regularized Non-Negative Matrix Factorization Method-Based Drug Repurposing for COVID-19

2021 ◽  
Vol 11 ◽  
Author(s):  
Xianfang Tang ◽  
Lijun Cai ◽  
Yajie Meng ◽  
JunLin Xu ◽  
Changcheng Lu ◽  
...  
Keyword(s):  
Matrix Factorization ◽  
De Novo ◽  
Characteristic Curve ◽  
Drug Repurposing ◽  
Factorization Method ◽  
Therapeutic Drugs ◽  
Indicator Matrix ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Non Negative Matrix Factorization

A novel coronavirus, named COVID-19, has become one of the most prevalent and severe infectious diseases in human history. Currently, there are only very few vaccines and therapeutic drugs against COVID-19, and their efficacies are yet to be tested. Drug repurposing aims to explore new applications of approved drugs, which can significantly reduce time and cost compared with de novo drug discovery. In this study, we built a virus-drug dataset, which included 34 viruses, 210 drugs, and 437 confirmed related virus-drug pairs from existing literature. Besides, we developed an Indicator Regularized non-negative Matrix Factorization (IRNMF) method, which introduced the indicator matrix and Karush-Kuhn-Tucker condition into the non-negative matrix factorization algorithm. According to the 5-fold cross-validation on the virus-drug dataset, the performance of IRNMF was better than other methods, and its Area Under receiver operating characteristic Curve (AUC) value was 0.8127. Additionally, we analyzed the case on COVID-19 infection, and our results suggested that the IRNMF algorithm could prioritize unknown virus-drug associations.

scholarly journals Drug Repurposing Commonly Against Dengue Virus Capsid and SARS-CoV-2 Nucleocapsid: An in Silico Approach

2020 ◽  
Author(s):  
Debica Mukherjee ◽  
Rupesh Roy ◽  
UPASANA RAY
Keyword(s):  
Dengue Virus ◽  
Capsid Protein ◽  
In Silico ◽  
Rna Binding ◽  
Drug Repurposing ◽  
Virus Capsid ◽  
Approved Drugs ◽  
Full Swing ◽  
Fda Approved Drugs ◽  
Virus Capsid Protein

<p></p><p>In the middle of SARS-CoV-2 pandemic, dengue virus (DENV) is giving a silent warning as the season approaches nearer. There is no specific antiviral against DENV for use in the clinics. Thus, considering these facts we can potentially face both these viruses together increasing the clinical burden. The search for anti-viral drugs against SARS-CoV-2 is in full swing and repurposing of already ‘in-use’ drugs against other diseases or COVID-19 has drawn significant attention. Earlier we had reported few FDA approved anti-viral and anti-microbial drugs that could be tested for binding with SARS-CoV-2 nucleocapsid N terminal domain. We explored the possibility of interactions of the drugs screened for SARS-CoV2 with Dengue virus capsid protein. We report five FDA approved drugs that were seen to be docking onto the SARS-CoV-2 nucleocapsid RNA binding domain, also docking well with DENV capsid protein on the RNA binding site and/or the capsid’s membrane fusion domain. Thus, the present study proposes these five drugs as common antiviral candidates against both SARS-CoV-2 and DENV although the <i>in silico</i> study is subject to further validations.</p><br><p></p>

scholarly journals In silico characterization of the NiRAN domain of RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV2

2020 ◽  
Author(s):  
Abhisek Dwivedy ◽  
Richard Mariadasse ◽  
Mohammed Ahmed ◽  
Deepsikha Kar ◽  
Jeyaraman Jeyakanthan ◽  
...  
Keyword(s):  
Active Site ◽  
In Silico ◽  
3D Structure ◽  
Drug Repurposing ◽  
The Novel ◽  
Lead Compounds ◽  
Nucleotidyl Transferase ◽  
Domain Organisation ◽  
Novel Coronavirus ◽  
In Silico Characterization

Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of the RdRp from the novel coronavirus – SARS-CoV2, provided the first ever insights into the domain organisation and possible functional characteristics of the NiRAN domain. Using in silico tools, this study predicts that the NiRAN domain assumes a kinase or phosphotransferase like fold and binds GTP and UTP at its proposed active site. Additionally, using molecular docking this study predicts the binding of five well characterized anti-microbial compounds at the NiRAN domain active site and their drug-likeliness and DFT properties. In line with the current global COVID-19 pandemic urgency, this study provides a new target and potential lead compounds for drug repurposing against SARS-CoV2.

Sign in / Sign up

Export Citation Format

Share Document