Evaluation of Traditional Ayurvedic Preparation for Prevention and Management of the Novel Coronavirus (SARS-CoV-2) Using Molecular Docking Approach

10.26434/chemrxiv.12110214 ◽

2020 ◽

Author(s):

Dharmendra Kumar Maurya ◽

Deepak Sharma

Keyword(s):

Molecular Docking ◽

Transmission Rate ◽

Black Pepper ◽

Virus Multiplication ◽

New Drugs ◽

Pharmacological Agents ◽

Target Proteins ◽

Prevention And Treatment ◽

Docking Approach ◽

Novel Coronavirus

Since the emergence of novel Coronavirus (SARS-CoV-2) infection in Wuhan, China in December 2019, it has now spread to over 205 countries. The ever-growing list of globally spread corona virus-19 disease (COVID19) patients has demonstrated the high transmission rate among human population. Although 12 new drugs are being tried for management of COVID19, currently there are no FDA approved drugs or vaccines to prevent and treat the infection of the SARS-CoV-2. Considering the current state of affairs, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of COVID19 by re-evaluating the knowledge of traditional medicines and repurposing of drugs. Here, we used molecular docking approach to explore the beneficial roles of an array of phytochemicals and active pharmacological agents present in the Indian herbs (Tulsi, Haldi, Giloy, Black pepper, Ginger, Clove, Cardamom, lemon, and Ashwagandha) which are widely used in the preparation of Ayurvedic medicines in the form of Kadha to control various respiratory disorders such as cough, cold and flu. The evaluation was made based on the docking scores calculated by AutoDock Vina. Our study has identified an array of phytochemicals present in these herbs which have significant docking scores and potential to inhibit different stages of SARS-CoV-2 infection as well as other Coronavirus target proteins. Molecular docking also indicated that, the phytochemicals present in these herbs possess significant anti-inflammatory property. Overall our study provides scientific justification in terms of binding of active ingredients present in different plants used in Kadha preparation with viral proteins and target proteins for prevention and treatment of the COVID19. This preparation can boost individual’s immunity and inhibit the viral severity by interfering at different stages of virus multiplication in the infected person.

Download Full-text

Evaluation of Traditional Ayurvedic Preparation for Prevention and Management of the Novel Coronavirus (SARS-CoV-2) Using Molecular Docking Approach

10.26434/chemrxiv.12110214.v2 ◽

2020 ◽

Author(s):

Dharmendra Kumar Maurya ◽

Deepak Sharma

Keyword(s):

Molecular Docking ◽

Transmission Rate ◽

Black Pepper ◽

Virus Multiplication ◽

New Drugs ◽

Pharmacological Agents ◽

Target Proteins ◽

Prevention And Treatment ◽

Docking Approach ◽

Novel Coronavirus

Since the emergence of novel Coronavirus (SARS-CoV-2) infection in Wuhan, China in December 2019, it has now spread to over 205 countries. The ever-growing list of globally spread corona virus-19 disease (COVID19) patients has demonstrated the high transmission rate among human population. Although 12 new drugs are being tried for management of COVID19, currently there are no FDA approved drugs or vaccines to prevent and treat the infection of the SARS-CoV-2. Considering the current state of affairs, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of COVID19 by re-evaluating the knowledge of traditional medicines and repurposing of drugs. Here, we used molecular docking approach to explore the beneficial roles of an array of phytochemicals and active pharmacological agents present in the Indian herbs (Tulsi, Haldi, Giloy, Black pepper, Ginger, Clove, Cardamom, lemon, and Ashwagandha) which are widely used in the preparation of Ayurvedic medicines in the form of Kadha to control various respiratory disorders such as cough, cold and flu. The evaluation was made based on the docking scores calculated by AutoDock Vina. Our study has identified an array of phytochemicals present in these herbs which have significant docking scores and potential to inhibit different stages of SARS-CoV-2 infection as well as other Coronavirus target proteins. Molecular docking also indicated that, the phytochemicals present in these herbs possess significant anti-inflammatory property. Overall our study provides scientific justification in terms of binding of active ingredients present in different plants used in Kadha preparation with viral proteins and target proteins for prevention and treatment of the COVID19. This preparation can boost individual’s immunity and inhibit the viral severity by interfering at different stages of virus multiplication in the infected person.

Download Full-text

Herbal Compounds from Syzygium aromaticum and Cassia acutifolia as a Shield against SARS-CoV-2 Mpro: a Molecular Docking Approach

Biointerface Research in Applied Chemistry ◽

10.33263/briac116.1485314865 ◽

2021 ◽

Vol 11 (6) ◽

pp. 14853-14865

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

New Drugs ◽

In Vivo Studies ◽

Syzygium Aromaticum ◽

Amino Acid Residues ◽

Ligand Interaction ◽

Docking Approach ◽

Novel Coronavirus

Novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was first identified in China in December 2019. Currently, the novel coronavirus disease 2019 (COVID-19) is the most infectious disease worldwide. In the absence of a vaccine or drug, herbal compounds may be used to treat or control this disease. To explore novel potent inhibitors that suppress this virus's growth, we performed molecular docking studies on SARS-CoV-2 Mpro using 17 effective herbal compounds, along with three reference drugs. Docking results showed that crategolic acid from Syzygium aromaticum (clove) had the highest binding affinity with SARS-CoV-2 Mpro protease, followed by sennoside (A, B, C, and D) compounds from Cassia acutifolia (Sana Makki). Crategolic acid and sennoside (A, B, C, and D) contain amino acid residues and hydrogen bonds involved in the protein-ligand interaction. The present study confirms that crategolic acid and sennoside represent the strongest potential inhibitors of SARS-CoV-2 Mpro. This study's results may help in vivo studies validate the usefulness of compounds from clove and Sana Makki in preparing herbal medicine for the treatment of COVID-19. This analysis supports the production of new drugs for the treatment and control of COVID-19.

Download Full-text

Computational Molecular Docking and Virtual Screening Revealed Promising SARS-CoV-2 Drugs

10.26434/chemrxiv.12237995.v1 ◽

2020 ◽

Cited By ~ 3

Author(s):

Maryam Hosseini ◽

Wanqiu Chen ◽

Charles Wang

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Virtual Screening ◽

Clinical Studies ◽

Inhibitory Effect ◽

Docking Approach ◽

Novel Coronavirus ◽

Approved Drugs ◽

Potential Inhibitors ◽

Computational Molecular Docking

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies.

Download Full-text

Investigation of the Anti-TB Potential of Selected Phytochemicals of Nigella Sativa using Molecular Docking Approach

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i45b32805 ◽

2021 ◽

pp. 278-286

Author(s):

Shabir Ahmad Mir

Keyword(s):

Molecular Docking ◽

Drug Targets ◽

Nigella Sativa ◽

New Drugs ◽

Docking Score ◽

Discovery Studio ◽

Biological Studies ◽

Docking Approach ◽

Novel Drug

Background: Tuberculosis (TB) is one of the foremost causes of human mortality across the world. In general, it is a curable disease and several drugs are available in market for its treatment, however, because of the drug resistance to the currently available anti-TB drugs, the development and/or discovery of new drugs with better efficacy against TB cannot be overlooked. In the present study, we performed virtual screening of the major phytochemicals of the plant Nigella sativa for investigating their potential to inhibit some novel drug targets of Mycobacterium tuberculosis, which included- pantothenate kinase, type 1 (MtPanK), β-ketoacyl ACP synthase I (MtKasA), and decaprenylphosphoryl-β-D-ribose 2′-epimerase 1 (MtDprE1). Methods: The screening of the phytochemicals was investigated through a molecular docking approach using Auto dock vina and the molecular interactions in the protein-ligand complexes were visualized and analysed through PyMol and BioVia Discovery Studio Visualizer. Results: Our in silico observations reveal that, out of the nine selected phytochemicals screened, five compounds, namely α-hederin, dithymoquinone, nigellidine, thymoquinone and thymol binded to one or more of the selected target enzymes with significant docking scores. α-hederin binded to MtDprE1 and MtKasA with a docking score of −8.5kcal/mol and −7.9kcal/mol, respectively, dithymoquinone binded to MtKasA, MtDprE1 and MtPanK with a docking score of −6.5kcal/mol, −8.2kcal/mol and −9.2kcal/mol, respectively and nigellidine binded to MtDprE1 and MtPanK with a docking score of −8.1kcal/mol and −8.2kcal/mol, respectively. Further, thymol as well as thymoquinone were observed to bind MtKasA with a docking score of −6.6kcal/mol. Conclusions: The results of our study indicate that the five phytochemicals of N. sativa, including α-hederin, dithymoquinone, nigellidine, thymoquinone and thymol, are worth studying further for their anti-TB activity, however, additional biological studies are warranted to validate these findings.

Download Full-text

Evaluation of Lens culinaris phytochemicals in binding to the 3C-like protease of SARS-CoV-2 – A molecular docking approach

Indian Journal of Medical Sciences ◽

10.25259/ijms_219_2020 ◽

2020 ◽

Vol 72 ◽

pp. 173-176

Author(s):

Anamul Hasan ◽

Rownak Jahan ◽

Khoshnur Jannat ◽

Tohmina Afroze Bondhon ◽

Md Shahadat Hossan ◽

...

Keyword(s):

Molecular Docking ◽

Lens Culinaris ◽

Docking Studies ◽

Polyphenolic Compounds ◽

Binding Affinities ◽

The Novel ◽

Molecular Docking Studies ◽

Docking Approach ◽

Novel Coronavirus ◽

Scientific Attention

The novel coronavirus known as SARS-CoV-2 and the virus-induced disease COVID-19 has caused widespread concerns due to its contagiousness, fatality rate, and the absence of drug(s). This study investigated Lens culinaris and its phytochemicals, especially the flavonoids. The compounds were assessed through molecular docking studies for their binding abilities with the major protease of the novel coronavirus, SARS-CoV-2 (PDB: 6LU7). A total of 42 phytochemicals of Lens culinaris were analyzed through molecular docking studies for their binding affinities to COVID 3C-like protease. Of them, 23 compounds were found to have binding affinities to the protease of −7.5 kcal/mol or higher. Our study indicates that Lens culinaris contains a number of polyphenolic compounds as well as phytosterols, which can bind to the active site of the protease, and so merits further scientific attention on trials for use as potential anti-COVID-19 drugs.

Download Full-text

Molecular Docking Studies of Bioactive Nicotiflorin against 6W63 Novel Coronavirus 2019 (COVID-19)

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200820162551 ◽

2020 ◽

Vol 23 ◽

Author(s):

Raghvendra Dubey ◽

Kushagra Dubey

Keyword(s):

Molecular Docking ◽

Data Bank ◽

Docking Studies ◽

Molecular Docking Studies ◽

Molegro Virtual Docker ◽

Main Protease ◽

Docking Approach ◽

Inhibitory Potential ◽

Efficacy Parameters ◽

Novel Coronavirus

Background: COVID-19 which is known as the novel coronavirus was reported in December 2019 in Wuhan city, China and many of the patients have been contaminated by environmental contamination and transmission from one human to another. Objective: The objective of work is to establish the inhibitory potential of nicotiflorin, a Kaempferol 3-O-rutinoside flavonoid, against the deadly coronavirus (COVID-19) 6W63 (main protease 3Clpro protein) , using molecular docking approach. Method: The Molegro Virtual Docker software (MVD) with a 30 Å grid resolution was used. The structure was drawn by Chem 3D software and energy minimization was done by the MM2 force field. The protein 6W63 was downloaded from the protein data bank. Molegro modeller was used for score calculations. Result: The molecular docking studies were carried out on nicotiflorin and standard inhibitor X77, where standard inhibitor was observed in a co-crystallized state with main protease 3Clpro protein 6W63. The MolDock score, Rerank Sore and H Bond score of nicotiflorin and standard inhibitor X77 was observed as -173.058, -127.302, -21.9398 and -156.913,- 121.296,-5.7369, respectively. Conclusion: Molecular docking studies have confirmed that the affinity of flavonoid nicotiflorin with the amino acids of the viral protein 6W63 was relatively more than the standard X77. For the effective treatment of novel coronavirus COVID-19, the effectiveness of the identified flavonoid nicotiflorin can further be evaluated for safety and efficacy parameters at both preclinical and clinical stages.

Download Full-text

Computational Molecular Docking and Virtual Screening Revealed Promising SARS-CoV-2 Drugs

10.26434/chemrxiv.12237995 ◽

2020 ◽

Author(s):

Maryam Hosseini ◽

Wanqiu Chen ◽

Charles Wang

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Virtual Screening ◽

Clinical Studies ◽

Inhibitory Effect ◽

Docking Approach ◽

Novel Coronavirus ◽

Approved Drugs ◽

Potential Inhibitors ◽

Computational Molecular Docking

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies.

Download Full-text

Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs

Precision Clinical Medicine ◽

10.1093/pcmedi/pbab001 ◽

2021 ◽

Author(s):

Maryam Hosseini ◽

Wanqiu Chen ◽

Daliao Xiao ◽

Charles Wang

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Protein Complexes ◽

Inhibitory Effect ◽

Dynamics Simulation ◽

The World ◽

Docking Approach ◽

Novel Coronavirus ◽

Approved Drugs ◽

Computational Molecular Docking

Abstract The pandemic of novel coronavirus disease 2019 (COVID-19) has rampaged the world with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by November 23, 2020. There is an urgent need to identify effective drugs and vaccines to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina, Glide, and rDock. Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2, including antiemetics Rolapitant and Ondansetron for Mpro; Labetalol and Levomefolic acid for PLpro; and Leucal and antifungal Natamycin for RdRp. Molecular dynamics simulation confirmed the stability of the ligand-protein complexes. The result of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins—Mpro, PLpro, and RdRp. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.

Download Full-text

Drug Repurposing Studies Targeting SARS-nCoV2: An Ensemble Docking Approach on Drug Target 3C-like Protease (3CLpro)

10.26434/chemrxiv.12228831 ◽

2020 ◽

Author(s):

Shruti Koulgi ◽

Vinod Jani ◽

Mallikarjunachari Uppuladinne ◽

Uddhavesh Sonavane ◽

Asheet Kumar Nath ◽

...

Keyword(s):

Drug Repurposing ◽

Drug Binding ◽

Ensemble Docking ◽

Drug Molecules ◽

Drug Binding Site ◽

Main Protease ◽

Docking Approach ◽

Novel Coronavirus ◽

Markov State Modeling ◽

Viral Polyprotein

The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CLpro (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This in-silico ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.

Download Full-text