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

In Silico Screening ◽

Main Protease ◽

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.

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 ◽

In Silico Screening ◽

Main Protease ◽

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 ◽

In Silico Screening ◽

Main Protease ◽

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.

FDA Approved Drugs and Herbal Based Inhibitors Target SARS CoV-2 RNA Dependent RNA Polymerase

Letters in Applied NanoBioScience ◽

10.33263/lianbs113.38113821 ◽

2021 ◽

Vol 11 (3) ◽

pp. 3811-3821

Keyword(s):

Rna Polymerase ◽

Drug Repurposing ◽

World Health ◽

In Vivo Studies ◽

Novel Coronavirus ◽

Health Organization ◽

Approved Drugs

The recent outburst of COVID-19 started as an epidemic in Wuhan city, China, in December 2019. It was declared a pandemic by World Health Organization on 30 January 2020. The rapid spread of the novel coronavirus leads to more deaths worldwide. Also, it has spared many lives in its second wave of disease in many countries. Although scientists had produced vaccines, it does not suit every human being, and they are getting infected again, which is due to a lack of extensive clinical trials. Also, drug repurposing is ineffective. There is a need for more research; using in silico methods may be the better option in the current situation to save the lives of virus-affected individuals. The drugs used for other diseases and herbal compounds might help target the coronavirus. In this study, a protein, RNA-dependent RNA polymerase (RdRp), was chosen as a target from the virus for molecular docking. It was docked against several drugs on the market and also several herbal compounds. This study will help further in vitro and in vivo studies with new lead compounds, new horizons for drugs in trials, and a new approach for Insilco analysis to treat COVID-19.

In silico SCREENING OF Ziziphus spina-christi (L.) Desf. AND Strychnos ligustrine COMPOUNDS AS A PROTEASE INHIBITOR OF SARS-COV-2

Journal of Experimental Biology and Agricultural Sciences ◽

10.18006/2021.9(spl-2-icopmes_2020).s208.s214 ◽

2021 ◽

Vol 9 (Spl-2-ICOPMES_2020) ◽

pp. S208-S214

Author(s):

Novi Yantih ◽

◽

Uthami Syabillawati ◽

Esti Mulatsari ◽

Wahono Sumaryono ◽

...

Keyword(s):

In Silico ◽

Data Bank ◽

Binding Pocket ◽

In Vivo Studies ◽

In Silico Screening ◽

Main Protease ◽

Docking Method ◽

Inhibitory Site

Diseases caused by the coronavirus have become an important concern in early 2020. The coronavirus is a new type of virus that is included in the SARS-CoV-2 group. One of the possible mechanisms of SARS-CoV-2 inhibition involves protease receptors inhibition. This research was aimed to in silico screening of Ziziphus spina-christi (L.) Desf., and Strychnos ligustrine active ingredients as the main protease inhibitors of SARS-CoV-2 by assessing the ligand-binding affinity in the binding pocket of SARS-CoV-2 main protease protein. The molecular docking method is generally used to predict the inhibitory site and bonds formation. In the current study, some generally used antiviral compounds from the PDB (Protein Data Bank) were also used to compare the affinity strength of the test compound against the protease receptor (code of 5R7Y). The inhibitory activity against the main protease receptor proven by the ChemPLP score is more negative than the receptor’s native ligand and the comparison compounds. Jubanine B, a compound of Z. spina-christi has the most robust inhibition activity on the SARS-CoV-2 protease receptor. Results of this study can be concluded that this can be used to develop as a candidate for traditional medicine against SARS-CoV-2 but still it required some more in vitro and in vivo studies.

Potential Candidates against COVID-19 Targeting RNA-Dependent RNA Polymerase: A Comprehensive Review

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210421102513 ◽

2021 ◽

Vol 22 ◽

Author(s):

Neetu Agrawal ◽

Ahsas Goyal

Keyword(s):

Rna Polymerase ◽

In Silico ◽

Host Cells ◽

In Vivo Experiments ◽

Contagious Nature ◽

In Silico Studies ◽

Viral Enzyme

: Due to the extremely contagious nature of SARS-COV-2, it presents a significant threat to humans worldwide. A plethora of studies are going on all over the world to discover the drug to fight SARS-COV-2. One of the most promising targets is RNA-dependent RNA polymerase (RdRp), responsible for viral RNA replication in host cells. Since RdRp is a viral enzyme with no host cell homologs, it allows the development of selective SARS-COV-2 RdRp inhibitors. A variety of studies used in silico approaches for virtual screening, molecular docking, and repurposing of already existing drugs and phytochemicals against SARS-COV-2 RdRp. This review focuses on collating compounds possessing the potential to inhibit SARS-COV-2 RdRp based on in silico studies to give medicinal chemists food for thought so that the existing drugs can be repurposed for the control and treatment of ongoing COVID-19 pandemic after performing in vitro and in vivo experiments.

Flavonoids and Nucleotide Analogs Show High Affinity for Viral Proteins of SARS-CoV-2 by in silico Analysis: New Candidates for the Treatment of COVID-19.

10.21203/rs.3.rs-67272/v1 ◽

2020 ◽

Author(s):

Luis Adrián De Jesús-González ◽

Juan Fidel Osuna-Ramos ◽

José Manuel Reyes-Ruiz ◽

Carlos Noe Farfan-Morales ◽

Selvin Noé Palacios-Rápalo ◽

...

Keyword(s):

Rna Polymerase ◽

Inhibitory Activity ◽

In Silico ◽

Antiviral Drug ◽

World Health ◽

Nucleotide Analogs ◽

High Affinity ◽

Uridine Nucleotide

Abstract The recent epidemic of COVID-19 caused by SARS-CoV-2 was declared by the World Health Organization as a public health emergency of international concern. The absence of an approved vaccine or a specific antiviral drug has made bioinformatic tools crucial for the identification of potential therapeutic targets and drugs for its control. As in other RNA viruses, the protease 3C-like and the RNA-polymerase are two of the SARS-CoV-2 targets to test drugs that can be analyzed in silico. In the present study, compounds derived from plants, fungi, and nucleoside 5'-triphosphate or uridine nucleotide analogs, with anti-DENV activity in vitro or in vivo, were analyzed by molecular docking as potential anti-SARS-CoV-2 drugs. Anthraquinone, with a DENV NS3 protease inhibitory activity; Balapiravir, Fisetin, Hyperoside, and Sofosbuvir, with a DENV NS5 RNA-polymerase inhibitory activity; and Quercetin, with both anti-NS3-NS5 activities, were tested against 3C-like protease and RNA-polymerase of SARS-CoV-2. All these drugs demonstrated a high affinity for the corresponding SARS-CoV-2 proteins, representing excellent candidates for the treatment of COVID-19. Therefore, in vitro or in vivo studies should be carried out using these compounds on models for SARS-CoV-2 infection.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

Current Pharmaceutical Design ◽

10.2174/1381612824666180327162357 ◽

2018 ◽

Vol 24 (10) ◽

pp. 1138-1147

Author(s):

Bruno Rivas-Santiago ◽

Flor Torres-Juarez

Keyword(s):

Pulmonary Tuberculosis ◽

Antimicrobial Peptides ◽

Experimental Models ◽

New Drugs ◽

World Health ◽

Public Health Issue ◽

Health Organization ◽

Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

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 ◽

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.

Virtual Screening and Statistical Analysis in the Design of New Caffeine Analogues Molecules with Potential Epithelial Anticancer Activity

Current Pharmaceutical Design ◽

10.2174/1381612823666170711112510 ◽

2018 ◽

Vol 24 (5) ◽

pp. 576-594 ◽

Cited By ~ 12

Author(s):

Josivan da Silva Costa ◽

Karina da Silva Lopes Costa ◽

Josiane Viana Cruz ◽

Ryan da Silva Ramos ◽

Luciane Barros Silva ◽

...

Keyword(s):

Anticancer Activity ◽

Binding Free Energy ◽

Inhibitory Effect ◽

Parametric Models ◽

World Health ◽

Pharmacokinetic Properties ◽

Clinically Significant ◽

About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the World Health Organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes.