In-Silico Screening of Phytochemicals in Febrifuges Used in Siddha Medicine for SARS-CoV-2 RNA Dependent RNA polymerase Inhibitory Activity

In an attempt to find potential antiviral agents, a series of pyrazolones (PA1-PA6& PC1-PC6) were designed and evaluated for their DENVNS5 (RNA-dependent RNA polymerase) inhibitory activity. Molecular docking studies of all the designed compounds into the binding site of DENVNS5 (PDB Code: 4C11) were performed to gain a comprehensive understanding into rational binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue PA6showed superior inhibitory activity against RNA dependent RNA polymerase. SAR study indicated that the presence of an electron withdrawing substitution on pyrazolone derivatives significantly improves its binding interaction with the protein.Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness.

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In silico Screening of Food Bioactive Compounds to Predict Potential Inhibitors of COVID-19 Main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

10.26434/chemrxiv.12051927.v2 ◽

2020 ◽

Cited By ~ 4

Author(s):

Brahmaiah Pendyala ◽

Ankit Patras

Keyword(s):

Rna Polymerase ◽

Bioactive Compounds ◽

In Silico ◽

World Health ◽

Rna Dependent Rna Polymerase ◽

In Silico Screening ◽

Main Protease ◽

Health Organization

As novel corona virus (COVID-19) infections has spread throughout the world, world health organization (WHO) has announced COVID-19 as a pandemic infection. Henceforth investigators are conducting extensive research to find possible therapeutic agents against COVID-19. Main protease (Mpro) that plays an essential role in processing the polyproteins that are translated from the 2019-nCOV RNA and RNA-dependent RNA polymerase (RdRp) that catalyzes the replication of RNA from RNA template becomes as a potential targets for in silico screening of effective therapeutic compounds to COVID-19. In this study we used COVID-19 Docking Server to predict potential food bioactive compounds to inhibit Mpro and RdRp. The results showed that Phycocyanobilin, Riboflavin, Cyanidin, Daidzein, Genistein are potent inhibitor bioactive compounds to Mpro and RdRp in comparison to antiviral drugs. Though, further in vitro and/or in vivo research is required to validate the docking results.

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In silico Screening of Food Bioactive Compounds to Predict Potential Inhibitors of COVID-19 Main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

10.26434/chemrxiv.12051927 ◽

2020 ◽

Cited By ~ 1

Author(s):

Brahmaiah Pendyala ◽

Ankit Patras

Keyword(s):

Rna Polymerase ◽

Bioactive Compounds ◽

In Silico ◽

World Health ◽

Rna Dependent Rna Polymerase ◽

In Silico Screening ◽

Main Protease ◽

Health Organization

As novel corona virus (COVID-19) infections has spread throughout the world, world health organization (WHO) has announced COVID-19 as a pandemic infection. Henceforth investigators are conducting extensive research to find possible therapeutic agents against COVID-19. Main protease (Mpro) that plays an essential role in processing the polyproteins that are translated from the 2019-nCOV RNA and RNA-dependent RNA polymerase (RdRp) that catalyzes the replication of RNA from RNA template becomes as a potential targets for in silico screening of effective therapeutic compounds to COVID-19. In this study we used COVID-19 Docking Server to predict potential food bioactive compounds to inhibit Mpro and RdRp. The results showed that Phycocyanobilin, Riboflavin, Cyanidin, Daidzein, Genistein are potent inhibitor bioactive compounds to Mpro and RdRp in comparison to antiviral drugs. Though, further in vitro and/or in vivo research is required to validate the docking results.

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In silico Screening of Food Bioactive Compounds to Predict Potential Inhibitors of COVID-19 Main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

10.26434/chemrxiv.12051927.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Brahmaiah Pendyala ◽

Ankit Patras

Keyword(s):

Rna Polymerase ◽

Bioactive Compounds ◽

In Silico ◽

World Health ◽

Rna Dependent Rna Polymerase ◽

In Silico Screening ◽

Main Protease ◽

Health Organization

As novel corona virus (COVID-19) infections has spread throughout the world, world health organization (WHO) has announced COVID-19 as a pandemic infection. Henceforth investigators are conducting extensive research to find possible therapeutic agents against COVID-19. Main protease (Mpro) that plays an essential role in processing the polyproteins that are translated from the COVID-19 RNA becomes and RNA-dependent RNA polymerase (RdRp) that catalyzes the replication of RNA from RNA template as a potential targets for in silico screening of effective therapeutic compounds to COVID-19. In this study we used COVID-19 Docking Server to predict potential food bioactive compounds to inhibit Mpro and RdRp. The results showed that Phycocyanobilin, Riboflavin, Cyanidin, Daidzein, Genistein are potent inhibitor bioactive compounds to Mpro and RdRp in comparison to antiviral drugs. Though, further in vitro and/or in vivo research is required to validate the docking results.

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Molecular Mechanisms of Several Novel Dipeptides with Angiotensin-Iconverting Enzyme Inhibitory Activity from In-silico Screening of Silkworm Pupae Protein

Current Pharmaceutical Biotechnology ◽

10.2174/138920101508140930153336 ◽

2014 ◽

Vol 15 (8) ◽

pp. 691-699 ◽

Cited By ~ 2

Author(s):

Wei Wang ◽

Yu Zhang ◽

Nan Wang ◽

Zuoyi Zhu

Keyword(s):

Inhibitory Activity ◽

In Silico ◽

Molecular Mechanisms ◽

In Silico Screening ◽

Silkworm Pupae

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In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases

Infectious Disorders - Drug Targets ◽

10.2174/1871526520666200727153643 ◽

2020 ◽

Vol 20 ◽

Cited By ~ 1

Author(s):

Trinath Chowdhury ◽

Gourisankar Roymahapatra ◽

Santi M. Mandal

Keyword(s):

Rna Polymerase ◽

Viral Entry ◽

In Silico ◽

Rna Dependent Rna Polymerase ◽

Replication Complex ◽

In Silico Study ◽

Life Threatening ◽

In Vivo Analysis ◽

3Cl Protease

Background: COVID-19 is a life threatening novel corona viral infection to our civilization and spreading rapidly. Terrific efforts are generous by the researchers to search for a drug to control SARS-CoV-2. Methods: Here, a series of arsenical derivatives were optimized and analyzed with in silico study to search the inhibitor of RNA dependent RNA polymerase (RdRp), the major replication factor of SARS-CoV-2. All the optimized derivatives were blindly docked with RdRp of SARS-CoV-2 using iGEMDOCK v2.1. Results: Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/mol) revealed most effective among them. Darinaparsin strongly binds with both Nsp9 replicase protein (-8.77 kcal/mol) and Nsp15 endoribonuclease (-8.3 kcal/mol) of SARS-CoV-2 as confirmed from the AutoDock analysis. During infection, the ssRNA of SARS-CoV2 is translated into large polyproteins forming viral replication complex by specific proteases like 3CL protease and papain protease. This is also another target to control the virus infection where darinaparsin also perform the inhibitory role to proteases of 3CL protease (-7.69 kcal/mol) and papain protease (-8.43 kcal/mol). Conclusion: In host cell, the furin protease serves as a gateway to the viral entry and darinaparsin docked with furin protease which revealed a strong binding affinity. Thus, screening of potential arsenic drugs would help in providing the fast invitro to in-vivo analysis towards development of therapeutics against SARS-CoV-2.

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