scholarly journals Favipiravir May Acts as COVID-19 Main Protease PDB ID 6LU7 Inhibitor: Docking Analysis

2020 ◽  
Vol 10 (6) ◽  
pp. 6821-6828 ◽  
Keyword(s):  
Amino Acids ◽  
Protease Inhibitor ◽  
Essential Amino Acids ◽  
Antiviral Drugs ◽  
Binding Pattern ◽  
Protease Inhibition ◽  
Docking Analysis ◽  
Protease Enzyme ◽  
Main Protease ◽  
Polymerase Inhibitor

Coronavirus is a well-known threat to the human being in the form of COVID-19. Virus replication may be controlled by inhibition of protease enzyme. Hence, well known 13 antiviral drugs have been observed by docking analysis for understanding the binding pattern of drugs with COVID-19 main protease PDB ID: 6LU7 for any possibilities of protease inhibition. For docking analysis PyRx- Python Prescription 0.8 was used. This analysis reveals that the essential amino acids involved in binding of antiviral drugs to COVID-19 main protease PDB ID: 6LU7 are Glycine (Gly), Serine (Ser), Cysteine (Cys), Leucine (Leu), Asparagine (Asn), Glutamine (Gln), Glutamic acid (Glu) and Threonine (Thr). After docking analysis, it was observed that Favipiravir maybe act as COVID-19 main protease inhibitor despite being vRNA polymerase inhibitor and may further be used in the treatment of COVID-19 infection.

scholarly journals Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir

2021 ◽  
Vol 102 (7) ◽  
Author(s):  
Marie O. Pohl ◽  
Idoia Busnadiego ◽  
Francesco Marrafino ◽  
Lars Wiedmer ◽  
Annika Hunziker ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Therapeutic Option ◽  
Cell Entry ◽  
Protease Inhibition ◽  
Antiviral Compounds ◽  
Main Protease ◽  
Anti Cancer ◽  
Synergistic Mechanism ◽  
Host Cell Entry

Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3 CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallel in vitro fluorescence-based protease-inhibition assays and Vero-CCL81 cell-based SARS-CoV-2 replication-inhibition assays were performed. One hit, diclazuril (an investigational anti-protozoal compound), was validated as a SARS-CoV-2 3 CL main protease inhibitor in vitro (IC50 value of 29 µM) and modestly inhibited SARS-CoV-2 replication in Vero-CCL81 cells. Another hit, lenvatinib (approved for use in humans as an anti-cancer treatment), could not be validated as a SARS-CoV-2 3 CL main protease inhibitor in vitro, but serendipitously exhibited a striking functional synergy with the approved nucleoside analogue remdesivir to inhibit SARS-CoV-2 replication, albeit this was specific to Vero-CCL81 cells. Lenvatinib is a broadly-acting host receptor tyrosine kinase (RTK) inhibitor, but the synergistic effect with remdesivir was not observed with other approved RTK inhibitors (such as pazopanib or sunitinib), suggesting that the mechanism-of-action is independent of host RTKs. Furthermore, time-of-addition studies revealed that lenvatinib/remdesivir synergy probably targets SARS-CoV-2 replication subsequent to host-cell entry. Our work shows that combining computational and cellular screening is a means to identify existing drugs with repurposing potential as antiviral compounds. Future studies could be aimed at understanding and optimizing the lenvatinib/remdesivir synergistic mechanism as a therapeutic option.

Virtual screening assisted identification of small molecule against 2019 novel coronavirus protease enzyme

2020 ◽  
Vol 7 ◽  
Author(s):  
Arkadeep Sarkar ◽  
Deepak Shilkar ◽  
Arindam Maity ◽  
Sarmi Sardar ◽  
Sudhan Debnath ◽  
...  
Keyword(s):  
Essential Amino Acids ◽  
Dynamics Simulation ◽  
Design Studies ◽  
Structure Based Drug Design ◽  
Protease Enzyme ◽  
Main Protease ◽  
Coronavirus Infection ◽  
The Stability ◽  
Novel Coronavirus ◽  
Global Threat

The 2019 novel coronavirus infection or COVID-19 can be designated as a global threat. Till date, there is a lack of dedicated therapeutics available against this fatal infection. In the present work, we performed structure-based drug design studies in order to identify clinically used molecules exhibiting crucial binding with 2019-coronavirus main protease enzyme. Based on ligand binding energy and interaction with essential amino acids, two molecules were selected. The stability of the complexed molecules with main protease enzyme was further studied by performing molecular dynamics simulation.

scholarly journals Structure-Based Virtual Screening: Identification of a Novel NS2B-NS3 Protease Inhibitor with Potent Antiviral Activity against Zika and Dengue Viruses

2021 ◽  
Vol 9 (3) ◽  
pp. 545
Author(s):  
Hye Jin Shin ◽  
Mi-Hwa Kim ◽  
Joo-Youn Lee ◽  
Insu Hwang ◽  
Gun Young Yoon ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Protease Activity ◽  
Therapeutic Option ◽  
Denv Infection ◽  
Antiviral Drugs ◽  
Protease Inhibition ◽  
Docking Analysis ◽  
Ns3 Protease ◽  
Protease Inhibition Assay

Zika virus (ZIKV), which is associated with severe diseases in humans, has spread rapidly and globally since its emergence. ZIKV and dengue virus (DENV) are closely related, and antibody-dependent enhancement (ADE) of infection between cocirculating ZIKV and DENV may exacerbate disease. Despite these serious threats, there are currently no approved antiviral drugs against ZIKV and DENV. The NS2B-NS3 viral protease is an attractive antiviral target because it plays a pivotal role in polyprotein cleavage, which is required for viral replication. Thus, we sought to identify novel inhibitors of the NS2B-NS3 protease. To that aim, we performed structure-based virtual screening using 467,000 structurally diverse chemical compounds. Then, a fluorescence-based protease inhibition assay was used to test whether the selected candidates inhibited ZIKV protease activity. Among the 123 candidate inhibitors selected from virtual screening, compound 1 significantly inhibited ZIKV NS2B-NS3 protease activity in vitro. In addition, compound 1 effectively inhibited ZIKV and DENV infection of human cells. Molecular docking analysis suggested that compound 1 binds to the NS2B-NS3 protease of ZIKV and DENV. Thus, compound 1 could be used as a new therapeutic option for the development of more potent antiviral drugs against both ZIKV and DENV, reducing the risks of ADE.

scholarly journals Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir

2021 ◽  
Author(s):  
Marie O. Pohl ◽  
Idoia Busnadiego ◽  
Francesco Marrafino ◽  
Lars Wiedmer ◽  
Annika Hunziker ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Therapeutic Option ◽  
Protease Inhibition ◽  
Antiviral Compounds ◽  
Main Protease ◽  
Ic50 Value ◽  
Anti Cancer ◽  
Synergistic Mechanism ◽  
Host Cell Entry

Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we screened by high-throughput docking 6,000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallel in vitro fluorescence-based protease-inhibition assays and Vero-CCL81 cell-based SARS-CoV-2 replication-inhibition assays were performed. One hit, diclazuril (an investigational anti-protozoal compound), was validated as a SARS-CoV-2 3CL main protease inhibitor in vitro (IC50 value of 29 μM) and modestly inhibited SARS-CoV-2 replication in Vero-CCL81 cells. Another hit, lenvatinib (approved for use in humans as an anti-cancer treatment), could not be validated as a SARS-CoV-2 3CL main protease inhibitor in vitro, but serendipitously exhibited a striking functional synergy with the approved nucleoside analogue remdesivir to inhibit SARS-CoV-2 replication in Vero-CCL81 cells. Lenvatinib is a broadly-acting host receptor tyrosine kinase (RTK) inhibitor, but the synergistic effect with remdesivir was not observed with other approved RTK inhibitors (such as pazopanib or sunitinib), suggesting that the mechanism-of-action is independent of host RTKs. Furthermore, time-of-addition studies revealed that lenvatinib/remdesivir synergy probably targets SARS-CoV-2 replication subsequent to host-cell entry. Our study shows that combining computational and cellular screening is an efficient means to identify existing drugs with repurposing potential as antiviral compounds. Future studies should aim at understanding and optimizing the lenvatinib/remdesivir synergistic mechanism as a therapeutic option.

scholarly journals Molecular Basis for ADP-ribose Binding to the Macro-X Domain of SARS-CoV-2 Nsp3

2020 ◽  
Author(s):  
David N. Frick ◽  
Rajdeep S. Virdi ◽  
Nemanja Vuksanovic ◽  
Narayan Dahal ◽  
Nicholas R. Silvaggi
Keyword(s):  
Amino Acids ◽  
Therapeutic Target ◽  
Molecular Basis ◽  
Nonstructural Protein ◽  
Structural Data ◽  
Antiviral Drugs ◽  
Potential Therapeutic Target ◽  
Main Protease ◽  
Rna Genome ◽  
Nonstructural Protein 3

ABSTRACTThe virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous proteins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymers, helicase and main protease, are well conserved between SARS-CoV-2 and the original SARS virus, but several others are not. This study examines one of the proteins encoded by SARS-CoV-2 that is most different, a macrodomain of nonstructural protein 3 (nsp3). Although 26% of the amino acids in this SARS-CoV-2 macrodomain differ from those seen in other coronaviruses, biochemical and structural data reveal that the protein retains the ability to bind ADP-ribose, which is an important characteristic of beta coronaviruses, and potential therapeutic target.

scholarly journals In Silico Docking Analysis of Poly Herbal Formulation Aadathodai Kudineer used in Siddha medicine in inhibiting Main Protease and ACE2 Receptor Spike protein SARS-CoV-2

2020 ◽  
Vol 11 (4) ◽  
pp. 765-772
Author(s):  
Nikil Niva J ◽  
Sasirekha R ◽  
Anbu N ◽  
Shree Devi M S ◽  
Sathiyarajeswaran P
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Specific Treatment ◽  
Spike Protein ◽  
World Health ◽  
Protease Inhibition ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Corona Virus ◽  
Main Protease

Corona virus disease (COVID-19) is an infectious pandemic disease caused by the newly discovered novel corona virus. World Health Organization has declared the global health emergency due to COVID19 outbreak. Currently, there is no specific treatment or vaccine for fighting against this infectious disease. Aadathodai Kudineer is a drug indicated for Iya Erumal, Kozhai Kattu, Kabasuram. Upon the mortality and severity of the disease COVID19, we tried to identify the possible inhibition of phytocomponents of Aadathodai Kudineer in inhibiting Main Protease and ACE2 Receptor Spike protein SARS-CoV-2 through molecular docking studies. Methodology: In Silico molecular docking analysis was performed for phytocomponents present in the Aadathodai Kudineer formulation for targets main protease and ACE2 Receptor Spike protein, PDB ID: 6LU7 and PDB ID: 2AJF using Autodock tool. ADME properties was also predicted for all the above compounds. Results: Among the 9 active Phytocompounds present in the Aadathodai Kudineer formulation, Lupeol showed high binding affinity with COVID19 main protease and ACE2 receptor which shows the promising contrivance of protease inhibition. The ADME suggested that the formulation is free from toxic. Conclusion: The phytocomponents showed possible affinity towards these targets and has the lead molecules that inhibits COVID19 main protease and ACE2 receptor. 

scholarly journals Interactions mechanism of commonly used drugs for the treatment of Covid-19

2021 ◽  
Vol 34 (3) ◽  
pp. 613-623
Author(s):  
S. Celik ◽  
A. D. Demirag ◽  
A. E. Ozel ◽  
S. Akyuz
Keyword(s):  
Binding Free Energy ◽  
Autodock Vina ◽  
Spike Glycoprotein ◽  
Docking Analysis ◽  
Drug Molecules ◽  
Protease Enzyme ◽  
Main Protease ◽  
Poisson Boltzmann ◽  
Approved Drugs ◽  
Fda Approved Drugs

In this study conformation analysis of seven drugs commonly used in the treatment of COVID-19 was performed. The most stable conformers of the drug molecules were used as initial data for docking analysis. Using the Cavityplus program, the probable most active binding sites of both apo and holo forms of COVID-19 main protease enzyme (Mpro) and spike glycoprotein of SARSCoV-2 receptors were determined. The interaction mechanisms of the 7 FDA approved drugs (arbidol, colchicine, dexamethasone, favipiravir, galidesivir, hydroxychloroquine, remdesivir) were examined using the AutoDock Vina program. The six of the seven drugs were found to be more stable in binding to apo form of COVID-19 Mpro and spike glycoprotein. Moreover, a set of molecular mechanics (MM) Poisson-Boltzmann (PB) surface area (SA) calculations on the investigated drugs-protein systems were performed and the estimated binding free energy of remdesivir and the apo form of Mpro system was found to be the best. The interaction results of FDA drugs with the apo form of COVID-19 Mpro and spike glycoprotein can play an important role for the treatment of COVID-19.                     KEY WORDS: COVID-19, Drugs, Molecular modelling, Conformational analysis, Molecular docking   Bull. Chem. Soc. Ethiop. 2020, 34(3), 613-623. DOI: https://dx.doi.org/10.4314/bcse.v34i3.16

Pengoptimalan Air Leri dalam Pembuatan Sabun Pembersih Wajah Alami yang Ekonomis

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Rahmawati Rahmawati ◽  
Trimayasari Trimayasari ◽  
Ghozali Akhmad Mustaqim ◽  
Wening Dwi Prastiwi ◽  
Emas Agus Prastyo Wibowo
Keyword(s):  
Amino Acids ◽  
Fine Particles ◽  
Hard Water ◽  
Essential Amino Acids ◽  
Ultraviolet Rays ◽  
Starch Granules ◽  
Facial Skin ◽  
Skin Cells ◽  
The Face ◽  
Made In

AbstractSoap facial cleanser is needed to keep the facial skin to keep them clean and healthy. The purpose of this study to make soap cleanser with natural materials such as hard water deposits leri. This is because the use of leri water starch or starch granules of fine particles contained in water leri dansel dust can shed the dead skin on the face because of the essential amino acids contained can regenerate skin cells. In addition, water leri can brighten the face because the leri water oryzanol contain substances that can update the development and formation of the pigment melanin, which is effectively to ward off ultraviolet rays. The process of making soap using the principle of saponification reaction, namely the reaction between the oil and the KOH/NaOH. Facial cleansing soap made in this study is solid soap. Based on the results of quality test, soap solid leri water has a pH of 11.1, saponification number is 33, the water content of 46% as well as respondents to the test aspects of aroma and foam shows good results so this water leri treatment can be an alternative solution to prevent the use of soap facial cleansers that contain harmful chemicals. Keywords: air leri, soap cleanser, saponification  AbstrakSabun pembersih wajah sangat diperlukan untuk menjaga kulit wajah agar tetap bersih dan sehat. Tujuan dari penelitian ini untuk membuat sabun pembersih wajah dengan bahan alami berupa endapan air leri. Penggunaan air leri ini dikarenakan butiran partikel starch atau pati halus yang terdapat dalam air leri dapat merontokkan debu dansel kulit mati pada wajah karena asam amino esensial yang terkandung dapat meregenerasi sel-sel kulit. Selain itu, air leri dapat mencerahkan wajah karena air leri mengandung zat oryzanol yang dapat memperbarui perkembangan dan pembentukan pigmen melanin, yang efektif guna menangkal sinar ultraviolet. Proses pembuatan sabun menggunakan prinsip reaksi saponifikasi, yaitu reaksi antara minyak dan KOH/NaOH. Sabun pembersih wajah yang dibuat dalam penelitian ini ialah sabun padat. Berdasarkan hasil uji mutu, sabun air leri padat memiliki pH 11,1, angka penyabunan sebesar 33 kadar air 46 kadar air 46 % serta uji responden terhadap aspek aroma dan busa yang menunjukkan hasil cukup baik sehingga pengolahan air leri ini dapat menjadi solusi alternative untuk mencegah penggunaan sabun pembersih wajah yang mengandung bahan kimia berbahaya. Kata kunci: air leri, sabun pembersih wajah, saponifikasi 

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