scholarly journals COV-Drug Target interaction server for Covid-19 Drug Repurposing

2021 ◽  
Author(s):  
Kamal Rawal ◽  
Prashant Singh ◽  
Robin Sinha ◽  
Priya Kumari ◽  
Swarsat Kaushik Nath ◽  
...  
Keyword(s):  
Drug Targets ◽  
Cathepsin L ◽  
Drug Repurposing ◽  
New Drugs ◽  
Pore Channel ◽  
Target Interaction ◽  
Viral Virulence ◽  
Cyclin G ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

The outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus has killed over 5 million people to date. So, there is an urgent requirement for new and effective medications that can treat the disease caused by SARS-CoV-2. To find new drugs, identification of drug targets is necessary (Chen et al., 2016). Number of research studies have identified therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis. Here we present a web enabled tool which helps in ranking the COVID-19 drugs based upon underlying molecular targets. The users are allowed to give drugs in SMILE format and the tools will provide the list of relevant targets related to COVID-19.

Interfering with Host Proteases in SARS-CoV-2 Entry as a Promising Therapeutic Strategy

2021 ◽  
Vol 28 ◽  
Author(s):  
Patrick Müller ◽  
Hannah Maus ◽  
Stefan Josef Hammerschmidt ◽  
Philip Knaff ◽  
Volker Mailänder ◽  
...  
Keyword(s):  
Cathepsin L ◽  
Cell Entry ◽  
New Drugs ◽  
Host Cells ◽  
S Protein ◽  
Cell Receptors ◽  
Current State ◽  
Causative Drug ◽  
Transmembrane Serine Protease ◽  
Global Threat

: Due to its fast international spread and substantial mortality, the coronavirus disease COVID-19 evolved to a global threat. Since currently, there is no causative drug against this viral infection available, science is striving for new drugs and approaches to treat the new disease. Studies have shown that the cell entry of coronaviruses into host cells takes place through the binding of the viral spike (S) protein to cell receptors. Priming of the S protein occurs via hydrolysis by different host proteases. The inhibition of these proteases could impair the processing of the S protein, thereby affecting the interaction with the host-cell receptors and preventing virus cell entry. Hence, inhibition of these proteases could be a promising strategy for treatment against SARS-CoV-2. In this review, we discuss the current state of the art of developing inhibitors against the entry proteases furin, the transmembrane serine protease type-II (TMPRSS2), trypsin, and cathepsin L.

scholarly journals Revealing new therapeutic opportunities through drug target prediction: a class imbalance-tolerant machine learning approach

2020 ◽  
Vol 36 (16) ◽  
pp. 4490-4497
Author(s):  
Siqi Liang ◽  
Haiyuan Yu
Keyword(s):  
Machine Learning ◽  
Drug Target ◽  
Drug Targets ◽  
Class Imbalance ◽  
Target Prediction ◽  
Drug Repurposing ◽  
New Drugs ◽  
Supplementary Information ◽  
Training Scheme ◽  
Drug Target Prediction

Abstract Motivation In silico drug target prediction provides valuable information for drug repurposing, understanding of side effects as well as expansion of the druggable genome. In particular, discovery of actionable drug targets is critical to developing targeted therapies for diseases. Results Here, we develop a robust method for drug target prediction by leveraging a class imbalance-tolerant machine learning framework with a novel training scheme. We incorporate novel features, including drug–gene phenotype similarity and gene expression profile similarity that capture information orthogonal to other features. We show that our classifier achieves robust performance and is able to predict gene targets for new drugs as well as drugs that potentially target unexplored genes. By providing newly predicted drug–target associations, we uncover novel opportunities of drug repurposing that may benefit cancer treatment through action on either known drug targets or currently undrugged genes. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals A network biology approach for identifying crucial host targets for COVID-19

2020 ◽  
Author(s):  
Ranjan Kumar Barman ◽  
Anirban Mukhopadhyay ◽  
Ujjwal Maulik ◽  
Santasabuj Das
Keyword(s):  
Drug Targets ◽  
Rna Synthesis ◽  
Interaction Network ◽  
Drug Repurposing ◽  
Adenosine Monophosphate ◽  
Network Biology ◽  
Centrality Measures ◽  
Potential Candidate ◽  
Human Proteins ◽  
Novel Coronavirus

In late December 2019, an outbreak of novel coronavirus SARS-CoV-2 originated in Wuhan city of china, has infected over 30,00,000 people worldwide. SARS-CoV-2 is a causative agent of COVID-19 that has killed over 2,11,000 people and created social and financial crisis globally. Currently, there is no effective antiviral drugs and vaccine available for the prevention of COVID-19. Therefore, the scientific community is more focused on drug repurposing for the treatment of COVID-19. Here, we propose a network biology approach to identify candidate biomarkers for COVID-19. We critically analyze SARS-CoV-2 targeted human proteins and their interaction network. We utilize a combination of essential network centrality measures and functional properties of human proteins to find the critical human targets for SARS-CoV-2 infection. From the candidate pool of 301 human proteins, interestingly we found that PRKACA, RHOA, CDK5RAP2, and CEP250 are candidates for therapeutic targets for COVID-19. PRKACA and CEP250 have also been found by another group for potential candidates for drug targets in treating COVID-19. We found that potential candidate drugs/compounds such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride for COVID-19. Most of the therapeutics development studies for COVID-19 are tried to block RNA synthesis through RNA dependent RNA Polymerase (RdRP). Our findings also suggest for blocking RNA synthesis in treating COVID-19.

scholarly journals Fighting COVID-19

2020 ◽  
Vol 80 (3) ◽  
pp. 698-701 ◽  
Author(s):  
D. M. O. Campos ◽  
C. B. S. Oliveira ◽  
J. M. A. Andrade ◽  
J. I. N. Oliveira
Keyword(s):  
Drug Targets ◽  
Vaccine Development ◽  
High Rate ◽  
The Novel ◽  
Rate Of Spread ◽  
Specific Effects ◽  
Main Protease ◽  
Clinical Strategies ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

Abstract The current COVID-19 pandemic caused by the novel coronavirus (SARS-CoV2) poses a threat to global health owing to its high rate of spread and severe forms of respiratory infection. The lack of vaccines and antivirals prevents clinical strategies against the disease, creating an emerging need for the development of safe and effective treatments. Strategies for vaccine development include complete vaccines against viruses, subunits, and nucleic acids, but are still in their early stages. Studies carried out to date on possible SARS-CoV2 drug targets highlight glycoprotein S, Mpro (main protease or protease type 3C), and a member of the transmembrane serine protease II families (TMPRSS2). However, due to the pandemic state, priority is given to marketed drugs. These include chloroquine (CQ), hydroxychloroquine (HCQ), nitazoxanide, remdesivir, Lopinavir/ritonavir (LPV / r), in addition to treatment with convalescent plasma. But, therapeutic specific effects against SARS-CoV2 have not yet been verified. Most of the information obtained about treatment is based on preliminary and limited studies. We conclude that, at this time of emergency, the search for new therapies is more urgent due to the need to save lives. Thus, we point out as interesting targets for future more specific research: glycoprotein S, Mpro, and TMPRSS2.

scholarly journals Characterization of structural and energetic differences between conformations of the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Rodrigo A. Moreira ◽  
Horacio V. Guzman ◽  
Subramanian Boopathi ◽  
Joseph L. Baker ◽  
Adolfo B. Poma
Keyword(s):  
Structural Stability ◽  
Drug Targets ◽  
Dynamic Contact ◽  
Cell Entry ◽  
New Drugs ◽  
Spike Protein ◽  
The Novel ◽  
Poisson Boltzmann ◽  
Novel Coronavirus

AbstractThe novel coronavirus disease 2019 (COVID-19) pandemic has disrupted modern societies and their economies. The resurgence in COVID-19 cases as part of the second wave is observed across Europe and the Americas. The scientific response has enabled a complete structural characterization of the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-CoV-2). Among the most relevant proteins required by the novel coronavirus to facilitate the cell entry mechanism is the spike protein trimer. This protein possesses a receptor-binding domain (RBD) that binds the cellular angiotensin-converting enzyme 2 (ACE2) and then triggers the fusion of viral and host cell membranes. In this regard, a comprehensive characterization of the structural stability of the spike protein is a crucial step to find new therapeutics to interrupt the process of recognition. On the other hand, it has been suggested the participation of more than one RBD as a possible mechanism to enhance cell entry. Here we discuss the protein structural stability based on the computational determination of the dynamic contact map and the energetic difference of the spike protein conformations via the mapping of the hydration free energy by the Poisson-Boltzmann method. We expect our result to foster the discussion of the number of RBD involved during recognition and the repurposing of new drugs to disable the recognition by discovering new hotspots for drug targets apart from the flexible loop in the RBD that binds the ACE2.

scholarly journals Characterization of Structural and Energetic Differences between Conformations of the SARS-CoV-2 Spike Protein

Materials ◽  
2020 ◽  
Vol 13 (23) ◽  
pp. 5362
Author(s):  
Rodrigo A. Moreira ◽  
Horacio V. Guzman ◽  
Subramanian Boopathi ◽  
Joseph L. Baker ◽  
Adolfo B. Poma
Keyword(s):  
Structural Stability ◽  
Drug Targets ◽  
Dynamic Contact ◽  
Cell Entry ◽  
New Drugs ◽  
Spike Protein ◽  
The Novel ◽  
Poisson Boltzmann ◽  
Novel Coronavirus

The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted modern societies and their economies. The resurgence in COVID-19 cases as part of the second wave is observed across Europe and the Americas. The scientific response has enabled a complete structural characterization of the Severe Acute Respiratory Syndrome—novel Coronavirus 2 (SARS-CoV-2). Among the most relevant proteins required by the novel coronavirus to facilitate the cell entry mechanism is the spike protein. This protein possesses a receptor-binding domain (RBD) that binds the cellular angiotensin-converting enzyme 2 (ACE2) and then triggers the fusion of viral and host cell membranes. In this regard, a comprehensive characterization of the structural stability of the spike protein is a crucial step to find new therapeutics to interrupt the process of recognition. On the other hand, it has been suggested that the participation of more than one RBD is a possible mechanism to enhance cell entry. Here, we discuss the protein structural stability based on the computational determination of the dynamic contact map and the energetic difference of the spike protein conformations via the mapping of the hydration free energy by the Poisson–Boltzmann method. We expect our result to foster the discussion of the number of RBD involved during recognition and the repurposing of new drugs to disable the recognition by discovering new hotspots for drug targets apart from the flexible loop in the RBD that binds the ACE2.

scholarly journals A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

2020 ◽  
Author(s):  
David E. Gordon ◽  
Gwendolyn M. Jang ◽  
Mehdi Bouhaddou ◽  
Jiewei Xu ◽  
Kirsten Obernier ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Affinity Purification ◽  
Drug Repurposing ◽  
Human Protein ◽  
Protein Protein Interaction ◽  
Human Proteins ◽  
Interaction Map ◽  
Novel Coronavirus ◽  
Approved Drugs

ABSTRACTAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

Understanding Membrane Protein Drug Targets in Computational Perspective

2019 ◽  
Vol 20 (5) ◽  
pp. 551-564 ◽  
Author(s):  
Jianting Gong ◽  
Yongbing Chen ◽  
Feng Pu ◽  
Pingping Sun ◽  
Fei He ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Membrane Protein ◽  
Drug Target ◽  
Drug Targets ◽  
Computational Models ◽  
Drug Repurposing ◽  
Protein Targets ◽  
Target Interaction ◽  
Alternative Understanding

Membrane proteins play crucial physiological roles in vivo and are the major category of drug targets for pharmaceuticals. The research on membrane protein is a significant part in the drug discovery. The biological process is a cycled network, and the membrane protein is a vital hub in the network since most drugs achieve the therapeutic effect via interacting with the membrane protein. In this review, typical membrane protein targets are described, including GPCRs, transporters and ion channels. Also, we conclude network servers and databases that are referring to the drug, drug-target information and their relevant data. Furthermore, we chiefly introduce the development and practice of modern medicines, particularly demonstrating a series of state-of-the-art computational models for the prediction of drug-target interaction containing network-based approach and machine-learningbased approach as well as showing current achievements. Finally, we discuss the prospective orientation of drug repurposing and drug discovery as well as propose some improved framework in bioactivity data, created or improved predicted approaches, alternative understanding approaches of drugs bioactivity and their biological processes.

scholarly journals Discovery of Anti-2019-nCoV Agents from 38 Chinese Patent Drugs toward Respiratory Diseases via Docking Screening

2020 ◽  
Author(s):  
Yong-Ming Yan ◽  
Xin Shen ◽  
Yong-Kai Cao ◽  
Jiao-Jiao Zhang ◽  
Yan Wang ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Drug Targets ◽  
Respiratory Diseases ◽  
Drug Repurposing ◽  
Botanical Knowledge ◽  
Main Protease ◽  
Common Strategy ◽  
Chinese Patent ◽  
Novel Coronavirus ◽  
Approved Drugs

The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

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