Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

2020 ◽  
Author(s):  
Vijay Kumar Vishvakarma ◽  
Kamlesh Kumari ◽  
PRASHANT SINGH
Keyword(s):  
Molecular Docking ◽  
Therapeutic Target ◽  
Antiviral Drugs ◽  
Basic Difference ◽  
Docking Result ◽  
Corona Virus ◽  
Main Protease ◽  
Positive Sense ◽  
New Form

<p>Nowadays, many people were dying due to infectious coronavirus diseases (COVID-19). It belongs to the betacoronavirus family and also known as SARS-CoV-2. However, COVID-19 is a new form that has some basic difference in the genome which makes it more lethal and infectious. In transmitted in human in late December 2019 and it infected about 20 million till date. Its genome is composed of positive-sense single-stranded RNA, which encodes for the poly-protein. This poly-protein further cleaved into various components of the virus to make the numerous copy of the virus. There are many more similarities in their genome among the SARS-CoV-2, SARS-CoV, MERS-CoV. However, protease proteins are responsible for the cleavage and hence, COVID-19 main protease is a prime therapeutic target. To date, no medicine/ vaccine can fully cure their infection. To inhibit the activity of protease of COVID-19, molecular docking and ADMET studies of 116 noscapine derivatives were performed and the result was compared with 14 reputed antiviral drugs including chloroquine and hydroxychloroquine. The molecular docking result indicates a better binding in comparison of 14 reputed drugs. Further, the top six noscapines was taken into consideration for the pose analysis and ADMET studies. Finally, the top six noscapine was refined by ADMET properties to get the most potent one.</p>

scholarly journals Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

2020 ◽  
Author(s):  
Vijay Kumar Vishvakarma ◽  
Kamlesh Kumari ◽  
PRASHANT SINGH
Keyword(s):  
Molecular Docking ◽  
Therapeutic Target ◽  
Antiviral Drugs ◽  
Basic Difference ◽  
Docking Result ◽  
Corona Virus ◽  
Main Protease ◽  
Positive Sense ◽  
New Form

<p>Nowadays, many people were dying due to infectious coronavirus diseases (COVID-19). It belongs to the betacoronavirus family and also known as SARS-CoV-2. However, COVID-19 is a new form that has some basic difference in the genome which makes it more lethal and infectious. In transmitted in human in late December 2019 and it infected about 20 million till date. Its genome is composed of positive-sense single-stranded RNA, which encodes for the poly-protein. This poly-protein further cleaved into various components of the virus to make the numerous copy of the virus. There are many more similarities in their genome among the SARS-CoV-2, SARS-CoV, MERS-CoV. However, protease proteins are responsible for the cleavage and hence, COVID-19 main protease is a prime therapeutic target. To date, no medicine/ vaccine can fully cure their infection. To inhibit the activity of protease of COVID-19, molecular docking and ADMET studies of 116 noscapine derivatives were performed and the result was compared with 14 reputed antiviral drugs including chloroquine and hydroxychloroquine. The molecular docking result indicates a better binding in comparison of 14 reputed drugs. Further, the top six noscapines was taken into consideration for the pose analysis and ADMET studies. Finally, the top six noscapine was refined by ADMET properties to get the most potent one.</p>

Computational screening of dual inhibitors from FDA approved antiviral drugs on SARS-CoV-2 spike protein and the main protease using molecular docking approach

2021 ◽  
Vol 65 (02) ◽  
pp. 160-172
Author(s):  
Shanthi Sabarimurugan ◽  
Indu Purushothaman ◽  
Rajarajan Swaminathan ◽  
Arun Dharmarajan ◽  
Sudha Warrier ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antiviral Drugs ◽  
Spike Protein ◽  
Computational Screening ◽  
Main Protease ◽  
Docking Approach ◽  
Dual Inhibitors

scholarly journals Molecular Docking Terhadap Senyawa Kurkumin dan Arturmeron pada Tumbuhan Kunyit (Curcuma Longa Linn.) yang Berpotensi Menghambat Virus Corona

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Tiara C. Pradani ◽  
. Fatimawali ◽  
Aaltje E. Manampiring ◽  
Billy J. Kepel ◽  
Fona D. Budiarso ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
In Silico ◽  
Virus Disease ◽  
Curcuma Longa ◽  
Positive Control ◽  
Tropical Plant ◽  
Corona Virus ◽  
Main Protease ◽  
Close Relationship

Abstract: At the end of 2019 the world was shocked by the emergence of a new virus, namely the corona virus (SARS-CoV 2) which is called Corona Virus Disease 2019 or COVID-19. The origin of the emergence of this virus is known to have originated in the city of Wuhan, Hubei Province, China in December 2019.1 Research shows a close relationship with the corona virus that causes Severe Acute Respitatory Syndrome (SARS) which broke out in Hong Kong in 2003, until WHO named it the novel corona virus ( nCoV19). Turmeric (Curcuma longa L.) is a tropical plant that has many benefits and is found in many parts of Indonesia. Turmeric is widely used by the community as a traditional medicine to treat several diseases, such as: anti-inflammatory, antioxidant, hepatoprotective, and others. This study aims to determine the content in several compounds in the turmeric plant that have the potential to inhibit COVID-19 by using the molecular docking method. Using the In Silico method, namely molecular docking with the compounds taken were curcumin and ar-turmerone and the main protease COVID-19 (6LU7). This study obtained the binding affinity of curcumin compounds, namely -7.2 and Ar-turmerone -5.8 compounds against Mpro COVID-19. Remdesivir, which was used as a positive control, had a binding affinity of -7.7. In conclusion, remdesivir got better results compared to curcumin and Ar-turmerone compounds.Keywords: Molecular Docking, Turmeric, COVID-19.  Abstrak: Pada akhir tahun 2019 dunia digemparkan dengan munculnya virus baru yaitu corona virus (SARS-CoV 2) yang disebut dengan Corona Virus Disease 2019 atau COVID-19. Awal mula munculnya virus ini diketahui berasal dari Kota Wuhan, Provinsi Hubei, China pada Desember 2019.1  Penelitian menunjukkan hubungan yang dekat dengan virus corona penyebab Severe Acute Respitatory Syndrome (SARS) yang mewabah di Hongkong pada tahun 2003, hingga WHO menamakannya sebagai novel corona virus (nCoV19). Kunyit (Curcuma longa L.) merupakan salah satu jenis tanaman tropis yang banyak memiliki manfaat dan banyak ditemukan di wilayah Indonesia. Kunyit banyak dimanfaatkan masyarakat sebagai obat tradisional untuk mengobati beberapa penyakit seperti: antiinflamasi, antioksidan, hepatoprotektor, dan lain-lain. Penelitian ini bertujuan untuk mengetahui kandungan dalam beberapa senyawa pada tumbuhan kunyit yang berpotensi menghambat COVID-19 dengan metode molecular docking. Menggunakan metode In Silico yaitu molecular docking dengan senyawa yang diambil adalah kurkumin dan ar-Turmerone dan main protease COVID-19 (6LU7). Penelitian ini didapatkan hasil binding affinity senyawa kurkumin yaitu -7.2 dan senyawa ar-turmeron -5.8 terhadap Mpro COVID-19. Remdesivir yang digunakan sebagai control positif mendapatkan hasil binding affinity yaitu -7.7. Sebagai simpulan, remdesivir mendapat hasil yang lebih baik dibandingkan dengan senyawa kurkumin dan ar-turmeron.Kata Kunci: Molecular Docking, Kunyit, COVID-19.

CORONAVIRUS AND ITS MAIN PROTEASE: AN INSIGHT FOR DRUGS DESIGN BY MOLECULAR DOCKING

2020 ◽  
Vol 6 (1) ◽  
pp. 73-83
Author(s):  
Simone Queiroga Brito Gonçalves ◽  
Eloi Alves Da Silva Filho ◽  
Osmair Vital De Oliveira ◽  
Arlan da Silva Gonçalves
Keyword(s):  
Molecular Docking ◽  
Structural Study ◽  
Work Motivation ◽  
Molecular Target ◽  
Antiviral Drugs ◽  
Viral Activity ◽  
Main Protease ◽  
Sulphydryl Groups ◽  
Potential Inhibitors ◽  
Interaction Between Drugs

Many virus need their sulphydryl groups to be reduced in order to be allowed to enter cells. SARS-CoV-2, which belongs to Coronaviridae family and is responsible for coronavirus disease 2019 or COVID-19, has cysteine-rich proteins in its capsid as the main CoV protease (MPRO), which must be intact and active maintaining the viral activity. Considering that MPRO is an important molecular target for development of antiviral drugs, this work motivation was the structural study of the possible ways of interaction between drugs and viral cysteines by molecular docking technique for design of new potential inhibitors of MPRO and its virulence.

Computational drug repurposing study of antiviral drugs against main protease, RNA polymerase, and spike proteins of SARS-CoV-2 using molecular docking method

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Alireza Jalalvand ◽  
Somayeh Behjat Khatouni ◽  
Zahra Bahri Najafi ◽  
Foroozan Fatahinia ◽  
Narges Ismailzadeh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
3D Structure ◽  
Drug Repurposing ◽  
Antiviral Drugs ◽  
Effective Drug ◽  
Main Protease ◽  
Docking Method ◽  
Inhibitory Potential ◽  
Molecular Docking Method

Abstract Objectives The new Coronavirus (SARS-CoV-2) created a pandemic in the world in late 2019 and early 2020. Unfortunately, despite the increasing prevalence of the disease, there is no effective drug for the treatment. A computational drug repurposing study would be an appropriate and rapid way to provide an effective drug in the treatment of the coronavirus disease of 2019 (COVID-19) pandemic. In this study, the inhibitory potential of more than 50 antiviral drugs on three important proteins of SARS-CoV-2, was investigated using the molecular docking method. Methods By literature review, three important proteins, including main protease, RNA-dependent RNA polymerase (RdRp), and spike, were selected as the drug targets. The three-dimensional (3D) structure of protease, spike, and RdRp proteins was obtained from the Protein Data Bank. Proteins were energy minimized. More than 50 antiviral drugs were considered as candidates for protein inhibition, and their 3D structure was obtained from Drug Bank. Molecular docking settings were defined using Autodock 4.2 software and the algorithm was executed. Results Based on the estimated binding energy of docking and hydrogen bond analysis and the position of drug binding, five drugs including, indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, had the highest inhibitory potential for all three proteins. Conclusions According to the results, among the mentioned drugs, saquinavir and lopinavir showed the highest inhibitory potential for all three proteins compared to the other drugs. This study suggests that saquinavir and lopinavir could be included in the laboratory phase studies as a two-drug treatment for SARS-CoV-2 inhibition.

scholarly journals Molecular docking of secondary metabolites from Indonesian marine and terrestrial organisms targeting SARS-CoV-2 ACE-2, M pro, and PL pro receptors

Pharmacia ◽  
2021 ◽  
Vol 68 (3) ◽  
pp. 533-560
Author(s):  
Gita Syahputra ◽  
Nunik Gustini ◽  
Bustanussalam Bustanussalam ◽  
Yatri Hapsari ◽  
Martha Sari ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Secondary Metabolites ◽  
Antiviral Drugs ◽  
Immunomodulatory Activity ◽  
Terrestrial Plants ◽  
Autodock Vina ◽  
Viral Proteases ◽  
Main Protease ◽  
Tremendous Importance

With the uncontrolled spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), development and distribution of antiviral drugs and vaccines have gained tremendous importance. This study focused on two viral proteases namely main protease (Mpro) and papain-like protease (PLpro) and human angiotensin-converting enzyme (ACE-2) to identify which of these are essential for viral replication. We screened 102 secondary metabolites against SARS-CoV-2 isolated from 36 terrestrial plants and 36 marine organisms from Indonesian biodiversity. These organisms are typically presumed to have antiviral effects, and some of them have been used as an immunomodulatory activity in traditional medicine. For the molecular docking procedure to obtain Gibbs free energy value (∆G), toxicity, ADME and Lipinski, AutoDock Vina was used. In this study, five secondary metabolites, namely corilagin, dieckol, phlorofucofuroeckol A, proanthocyanidins, and isovitexin, were found to inhibit ACE-2, Mpro, and PLpro receptors in SARS-CoV-2, with a high affinity to the same sites of ptilidepsin, remdesivir, and chloroquine as the control molecules. This study was delimited to molecular docking without any validation by simulations concerned with molecular dynamics. The interactions with two viral proteases and human ACE-2 may play a key role in developing antiviral drugs for five active compounds. In future, we intend to investigate antiviral drugs and the mechanisms of action by in vitro study.

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 Rapid structure-based identification of potential SARS-CoV-2 main protease inhibitors

2021 ◽  
Author(s):  
M Elizabeth Sobhia ◽  
G Siva Kumar ◽  
Srikanth Sivangula ◽  
Ketan Ghosh ◽  
Harmanpreet Singh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Natural Product ◽  
Protease Inhibitors ◽  
High Throughput ◽  
Data Bank ◽  
Antiviral Drugs ◽  
Combinatorial Structure ◽  
Main Protease ◽  
The World

The COVID-19 outbreak has thrown the world into an unprecedented crisis. It has posed a challenge to scientists around the globe who are working tirelessly to combat this pandemic. We herein report a set of molecules that may serve as possible inhibitors of the SARS-CoV-2 main protease. To identify these molecules, we followed a combinatorial structure-based strategy, which includes high-throughput virtual screening, molecular docking and WaterMap calculations. The study was carried out using Protein Data Bank structures 5R82 and 6Y2G. DrugBank, Enamine, Natural product and Specs databases, along with a few known antiviral drugs, were used for the screening. WaterMap analysis aided in the recognition of high-potential molecules that can efficiently displace binding-site waters. This study may help the discovery and development of antiviral drugs against SARS-CoV-2.

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