Discovery of Some Antiviral Natural products to fight against Novel Corona Virus (SARS-CoV-2) using Insilico approach

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

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Harnessing the Sars-cov-2 Spike Protein Binding Affinity to Ace2 Receptor Through Narcotinic Compounds Combined With Adjuvants: an in Silico Insight

10.21203/rs.3.rs-254891/v1 ◽

2021 ◽

Author(s):

Saeedeh Mohammadi ◽

Esmail Doustkhah ◽

Nader Sakhaee ◽

Ayoub Esmailpour ◽

Mohammad Esmailpour

Keyword(s):

Binding Affinity ◽

In Silico ◽

Muramyl Dipeptide ◽

Docking Studies ◽

Spike Protein ◽

Binding Affinities ◽

Narcotic Analgesics ◽

S Protein ◽

Suitable Combination ◽

Spike Proteins

Abstract Protein products of SARS-CoV-2 spike (S) coding gene sequence, were all analyzed and compared to other SARS-CoV S proteins to elucidate structural similarities of spike proteins. A homology modeling of SARS-CoV-2 S protein was obtained and used in molecular docking studies to find binding affinities of spike protein for angiotensin-converting enzyme 2 (ACE2). The two most important binding sites of S protein, namely, RBD and CTD, critically responsible for binding interactions, were identified. Finally, binding affinity of RBD and CTD domains of S protein with narcotic analgesics are studied. Moreover, interactions of ACE2 receptor- S protein with narcotic compounds when mixed with small molecule adjuvants to improve the immune response and increase the efficacy of potential vaccines, were taken into consideration. In-silico results suggest that the combination of narcotine hemiacetal with mannide monooleate shows a stronger binding affinity with CTD, while carprofen-muramyl dipeptide and squalene have stronger binding affinities for the RBD portion of S protein. Thus, a suitable combination of these narcotic is proposed to yield potent site-blocking efficacy for ACE2 receptor against SARS-CoV-2 spike proteins.

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Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification

Acta Pharmaceutica ◽

10.2478/acph-2022-0020 ◽

2021 ◽

Vol 72 (2) ◽

pp. 159-169

Author(s):

OLUWAKEMI EBENEZER ◽

MICHAEL SHAPI

Keyword(s):

Medicinal Plants ◽

Binding Affinity ◽

In Silico ◽

Complex Analysis ◽

Docking Studies ◽

Lipinski’S Rule ◽

Main Protease ◽

Pharmacokinetic Properties ◽

Lipinski’S Rule Of Five ◽

In Silico Identification

Abstract Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (–10.1 kcal mol–1), isotheaflavin-3’-gallate (–9.8 kcal mol–1), tomentin A and D (–8.0 and –8.8 kcal mol–1), theaflavin-3,3’-digallate (–8.6 kcal mol–1), papyriflavonol A (–8.4 kcal mol–1), iguesterin (–8.0 kcal mol–1) and savinin (–8.3 kcal mol–1) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski’s rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity may lead to discovering of anti-SARS CoV agents with promising safety profiles.

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

Jurnal e-Biomedik ◽

10.35790/ebm.v9i2.31888 ◽

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.

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Phytomolecules having flavone and napthofuran nucleus exhibited better binding G-score against protease and SPIKE protein of novel corona virus COVID-19

10.21203/rs.3.rs-27206/v1 ◽

2020 ◽

Author(s):

Karthik Aravinda Rajan A ◽

Muthusamy VS ◽

Ramanathan M

Keyword(s):

Virtual Screening ◽

Binding Affinity ◽

Disease Transmission ◽

Spike Protein ◽

Microbial Infection ◽

Human Immune System ◽

Ligand Interaction ◽

Corona Virus ◽

Specific Protease ◽

Justicia Adhatoda

Abstract The present study aims to screen the different phytoconstituents and drugs for potential treatment of the corona virus COVID-19 and for specificity through virtual screening. The plant molecules selected were based upon traditional knowledge and are prescribed in the Indian system of medicine for infectious/ respiratory conditions. The three target proteins selected for the study are 3CLpro, PLpro, and SPIKE. These proteins have defined pathological roles in disease transmission. The virtual screening was carried out in these proteins using the GLIDE Schrödinger Maestro software version 11.9.011. The efficacy was assessed by the calculated G-score of the ligand interaction with the amino acid side chains of the ligand binding domain. Molecules such as saponarin, mangiferin, and hesperidin exhibited better G-score with 3CLpro and PLpro. Similarly, diphyllin and tuberculatin exhibited better G-score for SPIKE protein. The reference anti malarial drug hydroxychloroquine showed better interactions with 3CLpro and PLpro. Similarly, protease inhibitors and antiviral drugs have shown interaction with 3CLpro specific protease protein. Interestingly, SPIKE protein ligands, diphyllin and tuberculatin from Justicia adhatoda (vasaka), were found to be unique and did not show affinity to protease inhibitor. It can be concluded, that the molecules having flavone scaffolds show better binding affinity with protease proteins 3CLpro and PLpro. SPIKE protein scaffold is different and showed better binding affinity with molecules having naptho-furan ring. The traditionally used plant phytoconstituents did not exhibit good binding affinity; however, we believe that a combination of these herbs might induce human immune system against microbial infection.

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Hydroxychloroquine (HCQ) exhibits better binding to the main protease (Mpro) compared to spike protein (S protein) of SARS-CoV-2: An in-silico analysis

Clinical Cancer Drugs ◽

10.2174/2212697x08666211210103711 ◽

2021 ◽

Vol 08 ◽

Author(s):

Deepa R. Bandi ◽

SubbaRao V. Tulimilli ◽

Durai Ananda Kumar T. ◽

Chandi Kumari Chitturi ◽

Anjalidevi S. Bettadapura ◽

...

Keyword(s):

Molecular Docking ◽

In Silico Analysis ◽

Protein S ◽

Data Bank ◽

Docking Studies ◽

Surface Glycoprotein ◽

Spike Glycoprotein ◽

S Protein ◽

Discovery Studio ◽

Main Protease

Background: Despite various efforts in preventing and treating SARS-CoV-2 infections; transmission and mortality have been increasing at alarming rates globally. Since its first occurrence in Wuhan, China, in December 2019, the number of cases and deaths due to SARS-CoV-2 infection continues to increase across 220 countries. Currently, there are about 228 million cases and 4.6 million deaths recorded globally. Although several vaccines/drugs have been reported to prevent or treat SARS-CoV-2, their efficacy to protect against emerging variants and duration of protection are not fully known. Hence, more emphasis is given to repurpose the existing pharmacological agents to manage the infected individuals. One such agent is hydroxychloroquine (HCQ), which is a more soluble derivative of antimalarial drug chloroquine. HCQ has been tested in clinical trials to mitigate SARS-CoV-2 infection-induced complications while reducing the time to clinical recovery (TTCR). However, several concerns and questions about the utility and efficacy of HCQ for treating SARS-CoV-2 infected individuals still persist. Identifying key proteins regulated by HCQ is likely to provide vital clues required to address these concerns. Objective: The objective of this study is to identify the ability of HCQ for binding to the most widely studied molecular targets of SARS-CoV-2 viz., spike glycoprotein (S protein), and main protease (Mpro, also referred as chymotrypsin like protease) using molecular docking approaches and correlate the results with reported mechanisms of actions of HCQ. Methods: X-ray crystallographic structures of spike glycoprotein and main protease of SARS-CoV-2 were retrieved from Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). The structure of Hydroxychloroquine was retrieved from the PubChem compound database. The binding interactions of the HCQ with target proteins were predicted using C-Docker algorithm, and visualized using Discovery studio visualizer. Results: Data from molecular docking studies showed very strong binding of HCQ to the main protease compared to spike glycoprotein. Conclusion: The antiviral activity of HCQ is attributed to its ability to bind to the main protease compared to surface glycoprotein. Therefore, future studies should focus more on developing a combination agent/strategy for targeting surface glycoprotein and main protease together.

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Docking Studies of Usnic Acid and Sodium Usnate on SARS CoV-2 Main Protease and Spike Protein RBD

10.26434/chemrxiv.12638906 ◽

2020 ◽

Author(s):

Roopa Guthappa

Keyword(s):

Infectious Disease ◽

Antiviral Agents ◽

Usnic Acid ◽

Docking Studies ◽

Spike Protein ◽

Binding Affinities ◽

Herbal Supplements ◽

Main Protease ◽

The World ◽

Mouth Wash

SARS CoV-2 a pandemic influenza like infectious disease emerged in December 2019 has spread throughout the world within few months. Scientists are trying their best to find medicine and vaccine. Usnic acid and its derivatives as herbal supplements are widely used as mouth wash, cosmetics, antiviral agents. In this study, usnic acid and its derivative-sodium usnate in comparison with favipiravir are docked with main protease and spike protein RBD 6M0J of SARS Cov-2. Usnic acid and sodium usnate exhibit better binding affinities for main protease and spike RBD. The data has been compared with favipiravir. Favipiravir, usnic acid, sodium usnate shows binding affinity of -4.25, -8.05 and -8.55 kcal/mol respectively with main protease. While favipiravir, usnic acid and sodium usnate exhibit binding affinities of -4.25, -6.02 and -6.53 kcal/mol with spike RBD respectively. One of the interesting features is that the inhibition constant values of usnic acid is 1.27 µM and sodium usnate is 539.86 nM in comparison to favipiravir (764.13 µM) with main protease.

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Compounds of Citrus medica and Zingiber officinale for COVID-19 inhibition: in silico evidence for cues from Ayurveda

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00171-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

M. Haridas ◽

Vijith Sasidhar ◽

Prajeesh Nath ◽

J. Abhithaj ◽

A. Sabu ◽

...

Keyword(s):

In Silico ◽

Active Sites ◽

Protein S ◽

Zingiber Officinale ◽

Nasal Carriage ◽

Docking Studies ◽

Spike Protein ◽

Viral Shedding ◽

In Silico Studies ◽

Citrus Medica

Abstract Background The nasal carriage of SARS-CoV-2 has been reported as the key factor transmitting COVID-19. Interventions that can reduce viral shedding from the nasopharynx could potentially mitigate the severity of the disease and its contagiousness. Herbal formulation of Citrus medica and Zingiber officinale is recommended in an Ayurvedic text as a nasal rinse in the management of contagious fevers. These herbs are also indicated in the management of respiratory illnesses and have been attributed with activity against pathogenic organisms in other texts. Molecular docking studies of the phytocompounds of C. medica and Z. officinale were done to find out whether these compounds could inhibit the receptor binding of SARS-CoV-2 spike protein (S protein) as well as the angiotensin-converting enzyme 2 (ACE-2), as evidenced from their docking into binding/active sites. Results The proteins of SARS-CoV-2, essential for its entry into human cells and highly expressed in the goblet and ciliated cells of nasal epithelium, play a significant role in contagiousness of the virus. Docking studies indicated that the specific compounds present in C. medica and Z. officinale have significant affinity in silico to spike protein of virus and ACE-2 receptor in the host. Conclusion In silico studies suggest that the phytochemical compounds in C. medica and Z. officinale may have good potential in reducing viral load and shedding of SARS-CoV-2 in the nasal passages. Further studies are recommended to test its efficacy in humans for mitigating the transmission of COVID-19.

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Virtual Screening of Novel Hybrid Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Exploring Multiple Targeted Cancer Therapy by an In Silico Approach

Current Cancer Therapy Reviews ◽

10.2174/1573394715666190618114748 ◽

2020 ◽

Vol 16 (1) ◽

pp. 70-77

Author(s):

Ashish P. Shah ◽

Chhagan N. Patel

Keyword(s):

Cancer Therapy ◽

Virtual Screening ◽

Binding Affinity ◽

Anticancer Agents ◽

In Silico ◽

Software Tool ◽

Docking Studies ◽

Targeted Cancer Therapy ◽

Bioactivity Prediction ◽

Glide Docking

Background: Dual-targeting/Multi-targeting of oncoproteins by a single drug molecule represents an efficient, logical and alternative approach to drug combinations. In silico methods are useful tool for the search and design of selective multi-target agents. Objective: The objective of the present study was to design new hybrid compounds by linking the main structural unit of the NSAIDs with the benzothiazole and thiadiazole ring and to discover new hybrid NSAIDs as multi targeted anticancer agents through in silico approach. Method: Structure-based virtual screening was performed by applying ADMET filtration and Glide docking using Virtual screening Workflow. The docking studies were performed on three different types of receptors TNF-α, COX-II and protein kinase. Bioactivity prediction of screened compounds were done using Molinspiration online software tool. Results: Out of 54 designed compounds eighteen were screened on the basis of binding affinity on various receptors and ADMET filtration. Bioactivity prediction reveals that screened compounds may act through kinase inhibition or enzyme inhibition. Compounds 2sa, 5sa, 6sa and 7sa shows higher binding affinity with all three receptors. Conclusion: The study concluded that compound 2sa, 5sa, 6sa, and 7sa could be further explored for multiple targeted cancer therapy.

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Β-SITOSTEROL: ISOLATION FROM MUNTINGIA CALABURA LINN BARK EXTRACT, STRUCTURAL ELUCIDATION AND MOLECULAR DOCKING STUDIES AS POTENTIAL INHIBITOR OF SARS-CoV-2 Mpro (COVID-19)

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i5.37909 ◽

2020 ◽

pp. 204-209

Author(s):

RAKESH N CHAUDHARI ◽

SHARUK L.KHAN ◽

RAVINDRA S CHAUDHARY ◽

SHIRISH P JAIN ◽

FALAK A SIDDUQUI

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Column Chromatography ◽

Docking Studies ◽

Bark Extract ◽

Molecular Docking Studies ◽

Ftir Characterization ◽

Main Protease ◽

Layer Chromatography ◽

Muntingia Calabura

Objecive: A novel human coronavirus (HCoV), labelled as SARS-CoV-2 (COVID-19), causing pneumonia is spreading around the world. At present, there are no specific treatments for COVID-19. β-sitosterol is well known for its multiple biological actions. The aim of this research is to isolate and study binding affinity of β-sitosterol for SARS-CoV-2 (COVID-19) main protease (Mpro). Methods: Extraction and Column chromatography was performed to isolate the β-sitosterol from n-hexane extract of Muntingia calabura bark followed by thin layer chromatography (TLC), HPTLC, FTIR and UV-Visible Spectroscopy. The molecular docking studies were performed on SARS-CoV-2 Mpro to determine the binding affinity of the β-sitosterol by using PyRx Virtual Screening Tool. Results: In present study, preliminary phytochemical screening showed presence of carbohydrate, steroid, terpenoid and flavonoid compounds. Total 115 fractions were collected from column chromatography by using benzene as solvent by isocratic elution technique. HPTLC Fingerprinting analysis showed the presence of β-sitosterol under 366 nm. FTIR characterization was performed of the same fraction which clearly gives the absorption peaks which resembles to β-sitosterol structure. Conclusion: The overall study concludes this method can be considered as a standard method for isolation of β-sitosterol from Muntingia calabura bark. Favipiravir have less binding affinity i.e. -5.7 kcal/mol than β-sitosterol which has -6.9 kcal/mol. The no. of hydrogen bonds formed by the Favipiravir is much more i.e. 04 than β-sitosterol which formed only 01 hydrogen bond with SARS-CoV-2 Mpro.

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Docking Studies of Usnic Acid and Sodium Usnate on SARS CoV-2 Main Protease and Spike Protein RBD

10.26434/chemrxiv.12638906.v1 ◽

2020 ◽

Author(s):

Roopa Guthappa

Keyword(s):

Infectious Disease ◽

Antiviral Agents ◽

Usnic Acid ◽

Docking Studies ◽

Spike Protein ◽

Binding Affinities ◽

Herbal Supplements ◽

Main Protease ◽

The World ◽

Mouth Wash

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