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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP5 (412)

ProteinS (63)

NSP3 (57)

ComplexRdRp (51)

ProteinN (11)


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SARS-CoV-2 Proteins
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    Virtual Screening and Molecular Dynamics on Blockage of Key Drug Targets as Treatment for COVID-19 MESHD Caused by SARS-CoV-2

    Authors: Ailan Huang; Xue Tang; Huimin Wu; Jun Zhang; Wanqi Wang; Zhiwei Wang; Li Song; Min-an Zhai; Lihui Zhao; Hailong Yang; Xiaohui Ma; Shuiping Zhou; Jinyong Cai

    id:202003.0239/v1 Date: 2020-03-15 Source: Preprints.org

    The current outbreak of coronavirus disease MESHD ( COVID-19 MESHD) caused by SARS-CoV-2 in Wuhan, China has killed more than 2600 people since December 2019. Currently there is no effective treatment for this epidemic. Drug for anti SARS-CoV-2 are urgently needed. In this study we evaluated two compound libraries containing launched drugs and compounds from 300 kinds of Traditional Chinese Medicine in order to find anti SARS-CoV-2 drugs. Docking and then calculating binding free energy were performed as workflow against four key anti-SARS-CoV-2 drug targets, 3CLpro PROTEIN, PLpro PROTEIN and RdRp PROTEIN from SARSCoV-2, and AAK1 HGNC from human as well. As a result, drugs launched with potential for antiviral usage were selected in the hope of providing some knowledge for future drug discovery.

    Potential Inhibitor of COVID-19 MESHD Main Protease PROTEIN ( Mpro PROTEIN) From Several Medicinal Plant Compounds by Molecular Docking Study

    Authors: Siti Khaerunnisa; Hendra Kurniawan; Rizki Awaluddin; Suhartati Suhartati; Soetjipto Soetjipto

    id:10.20944/preprints202003.0226.v1 Date: 2020-03-13 Source: Preprints.org

    COVID-19 MESHD, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 MESHD treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 MESHD main protease PROTEIN ( Mpro PROTEIN), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 MESHD Mpro PROTEIN inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 MESHD Mpro PROTEIN was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 MESHD Mpro PROTEIN inhibitors. However, further research is necessary to investigate their potential medicinal use.

    In Silico Fight Against Novel Coronavirus by Finding Chromone Derivatives as Inhibitor of Coronavirus Main Proteases PROTEIN Enzyme

    Authors: Nayim Sepay; Nadir Sepay; Ashique Al Hoque; Rina Mondal; Umesh Chandra Halder; Mohd. Muddassir

    doi:10.21203/rs.3.rs-17437/v1 Date: 2020-03-12 Source: ResearchSquare

    Novel coronavirus, 2019-nCoV is a danger to the world and is spreading rapidly. Very little structural information about 2019-nCoV make this situation more difficult for drug designing. Benzylidenechromanones, naturally occurring oxygen heterocyclic compounds, having capability to inhibit various protein and receptors, have been designed here to block mutant variety of coronavirus main protease PROTEIN enzyme (CoV Mpro PROTEIN ) isolated from 2019-nCoV with the assistance of molecular docking, bioinformatics and DFT. ( Z )-3-(4’-chlorobenzylidene)-thiochroman-4-one showed highest binding affinity to the protein. Binding of a compound to this protein actually inhibit the replication and transcription of the virus and ultimately, stop the virus multiplication. Incorporation of any functional groups to the basic benzylidenechromanones enhance their binding ability. Chloro and bromo substitution amplify the binding affinity. ADME studies of all these compounds indicates they are lipophilic, high gastro intestine absorbable and blood-brain barrier permeable. The outcome reveal that the investigated benzylidenechromanones can be examine in the case of 2019-nCoV as potent inhibitory drug of CoV M pro , for their strong inhibition ability, high reactivity, and effective pharmacological properties.

    Virtual Screening Based Prediction of Potential Drugs for COVID-19 MESHD

    Authors: Sekhar Talluri

    id:10.20944/preprints202002.0418.v2 Date: 2020-03-09 Source: Preprints.org

    SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 MESHD COVID-19 MESHD pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19 MESHD. The genomic sequence of the virus responsible for COVID-19 MESHD, as well as the experimentally determined three dimensional structure of the Main protease PROTEIN ( Mpro PROTEIN) are available. The reported structure of the target Mpro PROTEIN was utilized in this study to identify potential drugs for COVID-19 MESHD using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19 MESHD. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19 MESHD, based on predicted binding energy to the target Mpro of SARS-CoV-2 PROTEIN, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

    Virtual Screening of Approved Clinic Drugs with Main Protease PROTEIN ( 3CLpro PROTEIN) Reveals Potential Inhibitory Effects on SARS-CoV-2

    Authors: Qiang Wang; Ying Zhao; Xiaojia Chen; An Hong

    id:202003.0144/v1 Date: 2020-03-08 Source: Preprints.org

    3CLpro PROTEIN is the main protease PROTEIN of the novel coronavirus (SARS-CoV-2) responsible for their intracellular duplication. Based on virtual screening technology, we found 23 approved clinical drugs such as Carfilzomib, Saquinavir, Thymopentin and etc., which showed high affinity with the 3CLpro PROTEIN active sites. These findings suggest that 3CLpro PROTEIN inhibitors might be potential candidates for further activity detection and molecular modification.

    Substrate specificity profiling of SARS-CoV-2 Mpro PROTEIN protease provides basis for anti- COVID-19 MESHD drug design

    Authors: Wioletta Rut; Katarzyna Groborz; Linlin Zhang; Xinyuanyuan Sun; Mikolaj Zmudzinski; Bartlomiej Pawlik; Wojciech Mlynarski; Rolf Hilgenfeld; Marcin Drag

    doi:10.1101/2020.03.07.981928 Date: 2020-03-08 Source: bioRxiv

    In December 2019, the first cases of infection with a novel coronavirus, SARS-CoV-2, were diagnosed in Wuhan, China. Due to international travel and human-to-human transmission, the virus spread rapidly inside and outside of China. Currently, there is no effective antiviral treatment for coronavirus disease 2019 MESHD ( COVID-19 MESHD); therefore, research efforts are focused on the rapid development of vaccines and antiviral drugs. The SARS-CoV-2 main protease PROTEIN constitutes one of the most attractive antiviral drug targets. To address this emerging problem, we have synthesized a combinatorial library of fluorogenic substrates with glutamine in the P1 position. We used it to determine the substrate preferences of the SARS-CoV MESHD and SARS-CoV-2 main proteases PROTEIN, using natural and a large panel of unnatural amino acids. On the basis of these findings, we designed and synthesized an inhibitor and two activity-based probes, for one of which we determined the crystal structure of its complex with the SARS-CoV-2 Mpro PROTEIN. Using this approach we visualized SARS-CoV-2 active Mpro PROTEIN within nasopharyngeal epithelial cells of a patient with active COVID-19 MESHD infection. The results of our work provide a structural framework for the design of inhibitors as antiviral agents or diagnostic tests.

    AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2

    Authors: Bowen Tang; Fengming He; Dongpeng Liu; Meijuan Fang; Zhen Wu; Dong Xu

    doi:10.1101/2020.03.03.972133 Date: 2020-03-08 Source: bioRxiv

    The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected MESHD patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease PROTEIN ( 3CLpro PROTEIN or Mpro PROTEIN) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro PROTEIN. We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov. These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.

    Structural Elucidation of SARS-CoV-2 Vital Proteins: Computational Methods Reveal Potential Drug Candidates Against Main Protease PROTEIN, Nsp12 RNA-dependent RNA Polymerase PROTEIN and Nsp13 Helicase

    Authors: Muhammad Usman Mirza; Matheus Froeyen

    id:10.20944/preprints202003.0085.v1 Date: 2020-03-05 Source: Preprints.org

    The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a major outbreak of coronavirus disease 2019 MESHD ( COVID-19 MESHD) and instigated a widespread fear and has threatened global health security. Although phenomenal efforts are in progress to effectively combat this COVID-19 MESHD outbreak. Still, no licensed antiviral drugs or vaccines are available, and treatment is limited to supportive care and few repurposed drugs. In this urgency situation, computational drug discovery methods provide both an alternative and a supplement to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has shown the most successful strategy in antiviral drug discovery. The present study deals with the identification of potential compounds that specifically interact with SARS-CoV-2 vital proteins, including main protease PROTEIN ( Mpro PROTEIN), Nsp12 RNA-dependent-RNA-polymerase PROTEIN ( RdRp PROTEIN) and Nsp13 helicase. A constructive and integrated virtual screening efforts together with molecular dynamics simulations identified potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, structurally important binding site residues in conserved motifs located inside the active site are elucidated, which displayed relative importance in ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study paved the way to identify and design specific targeted inhibitors to combat COVID-19 MESHD outbreak.

    Targeted Oxidation Strategy (TOS) for Potential Inhibition of Coronaviruses by Disulfiram — a 70-Year Old Anti-Alcoholism Drug

    Authors: Luyan Xu; Jiahui Tong; Yiran Wu; Suwen Zhao; Bo-Lin Lin

    doi:10.26434/chemrxiv.11936292.v1 Date: 2020-03-05 Source: ChemRxiv

    In the new millennium, the outbreak of new coronavirus has happened three times: SARS-CoV, MERS-CoV, and 2019-nCoV. Unfortunately, we still have no pharmaceutical weapons against the diseases caused by these viruses. The pandemic of 2019-nCoV reminds us of the urgency to search new drugs with totally different mechanism that may target the weaknesses specific to coronaviruses. Herein, we disclose a new targeted oxidation strategy (TOS II) leveraging non-covalent interactions potentially to oxidize and inhibit the activities of cytosolic thiol proteins via thiol/thiolate oxidation to disulfide (TOD). Quantum mechanical calculations show encouraging results supporting the feasibility to selectively oxidize thiol of targeted proteins via TOS II even in relatively reducing cytosolic microenvironments. Molecular docking against the two thiol proteases Mpro PROTEIN and PLpro PROTEIN of 2019-nCoV provide evidence to support a TOS II mechanism for two experimentally identified anti-2019-nCoV disulfide oxidants: disulfiram and PX-12. Remarkably, disulfiram is an anti-alcoholism drug approved by FDA 70 years ago, thus it can be immediately used in phase III clinical trial for anti-2019-nCoV treatment. Finally, a preliminary list of promising TOS II drug candidates targeting the two thiol proteases of 2019-nCoV are proposed upon virtual screening of 32143 disulfides.

    Molecular Dynamics Simulations Indicate the COVID-19 MESHD Mpro PROTEIN Is Not a Viable Target for Small-Molecule Inhibitors Design

    Authors: Maria Bzowka; Karolina Mitusinska; Agata Raczynska; Aleksandra Samol; Jack Adam Tuszynski; Artur Gora

    doi:10.1101/2020.02.27.968008 Date: 2020-03-02 Source: bioRxiv

    The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mix-solvent molecular dynamics simulations of the main protease PROTEIN ( Mpro PROTEIN) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar SARS Mpro PROTEIN protein. In spite of a high level of sequence similarity, the active sites in both proteins show major differences in both shape and size indicating that repurposing SARS drugs for COVID-19 MESHD may be futile. Furthermore, analysis of the binding sites conformational changes during the simulation time indicates its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicates that the virus mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro PROTEIN inhibitor design.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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