scholarly journals In silico screening of Moroccan medicinal plants with the ability to directly inhibit the novel coronavirus, SARS-CoV-2

2020 ◽  
Author(s):  
Reda Ben Mrid ◽  
Najat Bouchmaa ◽  
Imad Kabach ◽  
Mansour Sobeh ◽  
Abdelmajid Zyad ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
In Silico ◽  
Literature Search ◽  
Natural Compounds ◽  
The Novel ◽  
In Silico Screening ◽  
Adme Properties ◽  
Orally Bioavailable ◽  
Novel Coronavirus ◽  
Natural Inhibitors

Abstract In the present study, we investigated natural compounds contained in Moroccan medicinal plants and that might be used as natural inhibitors of the novel coronavirus, SARS-CoV-2, that causes coronavirus disease 2019 (COVID-19). We first performed a literature search for natural inhibitors of SARS or MERS coronaviruses. We then selected natural compounds that have been biologically tested and confirmed to possess anti-coronavirus activity. Subsequently, we used a molecular docking to determine whether the selected molecules could interact with the virus proteins. The compounds selected from virtual screening were then subjected to an in-silico analysis of absorption, distribution, metabolism and excretion (ADME) properties to select only natural compounds that could be orally bioavailable. Thereafter, a second search has been launched to select Moroccan medicinal plants that contain at least 3 molecules from those natural compounds. As results, among 41 natural inhibitors of SARS or MERS coronaviruses, only 13 have been successfully passed the ADME filtering. These molecules, showed abilities to interact with the novel coronavirus as it was predicted. Using these molecules and based on the data extracted from literature, 29 Moroccan medicinal plants have been found to contain at least 3 of these coronavirus inhibitors. Therefore, the medicinal plants selected in this study might contain direct anti-SARS-CoV-2 compounds.

scholarly journals In silico screening of mint leaves compound (Mentha piperita L.) as a potential inhibitor of SARS-CoV-2

2021 ◽  
pp. 81-86
Author(s):  
Diana Serlahwaty ◽  
Cindy Giovani
Keyword(s):  
Amino Acids ◽  
In Silico ◽  
Mentha Piperita ◽  
The Novel ◽  
In Silico Screening ◽  
Comparison Results ◽  
Study Results ◽  
Herbal Plants ◽  
The One ◽  
Novel Coronavirus

Introduction: The novel coronavirus in Wuhan, China, was identified at the end of December 2019 and resulted in a global outbreak. Therefore, it is necessary to perform screening of compounds in herbal plants with antiviral potential against COVID-19. Mint leaves (Mentha piperita L.) were reported as one of the proposed samples, and this study was performed in silico to evaluate the antiviral activity of the content. Methods: The proposed mechanism of action includes the inhibition of SARS-CoV-2 proteins from binding with the receptor. Subsequently, several receptors associated with SARS-CoV-2 were validated, and the one with the code PDB 5R7Y and an RMSD value of 1.9974 Å was obtained using the YASARA application. This study was performed on 15 virtual mint leaves and five previously studied comparison compounds with inhibitory capacity. Therefore, docking started with the PLANTS application, and the results were visualised using PyMol to further identify the amino acids contained in the ligand, while the statistical t-test was used for comparison. Results: The study results showed the existence of active compounds in mint leaves, including rutin, hesperidin, and isorhoifolin.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

2020 ◽  
Vol 16 ◽  
Author(s):  
Bichismita Sahu ◽  
Santosh Kumar Behera ◽  
Rudradip Das ◽  
Tanay Dalvi ◽  
Arnab Chowdhury ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Peptide Nucleic Acid ◽  
Large Set ◽  
Nonstructural Proteins ◽  
In Silico Screening ◽  
Replication Process ◽  
Enveloped Virus ◽  
Treatment Regimens ◽  
Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

Screening of phytochemicals from Curcuma longa for their inhibitory activity on SARS-CoV-2: An in-silico study

2021 ◽  
Vol 19 ◽  
Author(s):  
Preeya Negi ◽  
Lalita Das ◽  
Surya Prakash ◽  
Vaishali M. Patil
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
Curcuma Longa ◽  
Docking Studies ◽  
Primary Objective ◽  
In Silico Screening ◽  
Rational Drug ◽  
In Silico Study ◽  
Speed Up ◽  
Novel Coronavirus

Introduction: Natural products or phytochemicals have always been useful as effective therapeutics and for providing the lead for rational drug discovery approaches specific to anti-viral therapeutics. Methods: The ongoing pandemic caused by novel coronavirus has created a demand for effective therapeutics. Thus, to achieve the primary objective to search for effective anti-viral therapeutics, in silico screening of phytochemicals present in Curcuma longa extract (ex. Curcumin) has been planned. Results: The present work involves the evaluation of ADME properties and molecular docking studies. Conclusion: The application of rationalized drug discovery approaches to screen the diverse natural resources will speed up the anti-COVID drug discovery efforts and benefit the global community.

In Silico Approaches for Novel Drug Discovery Against Coronavirus by Employing the Hybrid Molecular Technique: A Review

2021 ◽  
pp. 1-8
Author(s):  
Noor ul Amin Mohsin ◽  
Muhammad Irfan ◽  
Muhammad Naeem Aamir
Keyword(s):  
In Silico ◽  
Antiviral Agent ◽  
Molecular Technique ◽  
The Novel ◽  
Hybrid Molecules ◽  
The World ◽  
Being There ◽  
Novel Coronavirus ◽  
Novel Drug ◽  
Day By Day

The coronavirus disease (COVID-19) is causing havoc all around the world. The number of active cases and deaths is increasing day by day. The novel coronavirus (CoV) is the causative agent of this disease. For the time being, there is no specific antiviral agent for the cure of COVID-19. A variety of drugs are being repurposed to counteract this disease. Scientists all over the world are striving to get some ideal molecules against this pandemic. Some hybrid molecules have been designed by coupling the privileged scaffolds of known antiviral and antimalarial drugs. This review deals with the hybrid molecules that have been designed and evaluated against the known targets of CoV by in silico techniques.

scholarly journals In silico Design of Novel N-hydrosulfonylbenzamides inhibitors of dengue RNA-dependent RNA polymerase showing favorable predicted pharmacokinetic profiles

2021 ◽  
Vol 5 (2) ◽  
pp. 561-584
Author(s):  
Kouakou Kouakou Jean-Louis ◽  
◽  
Melalie Keita ◽  
Akori Elvice Esmel ◽  
Brice Dali ◽  
...  
Keyword(s):  
Gas Phase ◽  
In Silico ◽  
Pharmacophore Model ◽  
Pharmacokinetic Profile ◽  
Qsar Model ◽  
Active Conformation ◽  
Rna Dependent Rna Polymerase ◽  
In Silico Screening ◽  
Lipinski’S Rule ◽  
Adme Properties

Background: In recent years, there has been a growing interest in Denv NS5 inhibition, with several reported RdRp inhibitors such as sulfonylbenzamides, non-nucleo-side inhibitors without any 3D-QSAR pharmacophore (PH4) available. In this context, we report here, in silico design and virtual evaluation of novel sulfonylbenzamides Denv RdRp inhibitors with favorable predicted pharmacokinetic profile. Methods: By using in situ modifications of the crystal structure of 5-(5-(3-hydroxyprop-1-yn-1-yl)thiophen-2-yl)-4- methoxy-2-methyl-N-(methylsulfonyl) benzamide (EHB)-RdRp complex (PDB entry 5HMZ), 3D models of RdRp-EHBx complexes were prepared for a training set of 18 EHBs with experimentally determined inhibitory potencies (half-maximal inhibitory concentrations IC50exp). In the search for active conformation of the EHB1-18, linear QSAR model was prepared, which correlated computed gas phase enthalpies of formation ∆∆HMM of RdRp-EHBx complexes with the IC50exp. Further, considering the solvent effect and entropy changes upon ligand binding resulted in a superior QSAR model correlating computed complexation Gibbs free energies (∆∆Gcom). The successive pharmacophore model (PH4) generated from the active conformations of EHBs served as a virtual screening tool of novel analogs included in a virtual combinatorial library (VCL) of compounds with scaffolds restricted to phenyl. The VCL filtered by the Lipinski’s rule-of-five was screened by the PH4 model to identify new EHB analogs. Results: Gas phase QSAR model: -log10(IC50exp) = p IC50exp =-0.1403 x ∆∆HMM _ 7.0879, R2 = 0.73; superior aqueous phase QSAR model: p IC50exp = -0.2036 x ∆∆Gcom + 7.4974, R2 = 0.81 and PH4 pharmacophore model: p IC50exp = 1.0001 x p IC50pre -0.0017, R2 = 0.97. The VCL of more than 30 million EHBs was filtered down to 125,915 analogs Lipinski’s rule. The five-point PH4 screening retained 329 new and potent EHBs with predicted inhibitory potencies p IC50pre up to 30 times lower than that of EHB1 (IC50exp = 23nM). Predicted pharmacokinetic profile of the new analogs showed enhanced cell membrane permeability and high human oral absorption compared to the alone drug to treat dengue virus. Conclusions: Combined use of QSAR models, which considered binding of the EHBs to RdRp, pharmacophore model and ADME properties helped to recognize bound active conformation of the sulfonylbenzamide inhibitors, permitted in silico screening of VCL of compounds sharing sulfonylbenzamide scaffold and identify new analogs with predicted high inhibitory potencies and favorable pharmacokinetic profiles. Keywords: ADME properties prediction, Dengue, 3-(5-ethynylthiophen-2-yl)-N-hydrosulfonylbenzamides, in silico screening, RNA-dependent RNA polymerase.

scholarly journals Clinical Progress Note: Point-of-Care Ultrasound Applications in COVID-19

2020 ◽  
Vol 15 (6) ◽  
pp. 353-355 ◽  
Author(s):  
Benji K Mathews ◽  
Seth Koenig ◽  
Linda Kurian ◽  
Benjamin Galen ◽  
Gregory Mints ◽  
...  
Keyword(s):  
Septic Shock ◽  
Respiratory Failure ◽  
Critical Illness ◽  
Literature Search ◽  
Point Of Care ◽  
Severe Illness ◽  
Point Of Care Ultrasound ◽  
The Novel ◽  
Novel Coronavirus ◽  
Ultrasound Applications

COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, was declared a pandemic on March 11, 2020. Although most patients (81%) develop mild illness, 14% develop severe illness, and 5% develop critical illness, including acute respiratory failure, septic shock, and multiorgan dysfunction.1 Point-of-care ultrasound (POCUS), or bedside ultrasound performed by a clinician caring for the patient, is being used to support the diagnosis and serially monitor patients with COVID-19. We performed a literature search of electronically discoverable peer-reviewed publications on POCUS use in COVID-19 from December 1, 2019, to April 10, 2020. We review key POCUS applications that are most relevant to frontline providers in the care of COVID-19 patients.

scholarly journals In silico characterization of the NiRAN domain of RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV2

2020 ◽  
Author(s):  
Abhisek Dwivedy ◽  
Richard Mariadasse ◽  
Mohammed Ahmed ◽  
Deepsikha Kar ◽  
Jeyaraman Jeyakanthan ◽  
...  
Keyword(s):  
Active Site ◽  
In Silico ◽  
3D Structure ◽  
Drug Repurposing ◽  
The Novel ◽  
Lead Compounds ◽  
Nucleotidyl Transferase ◽  
Domain Organisation ◽  
Novel Coronavirus ◽  
In Silico Characterization

Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of the RdRp from the novel coronavirus – SARS-CoV2, provided the first ever insights into the domain organisation and possible functional characteristics of the NiRAN domain. Using in silico tools, this study predicts that the NiRAN domain assumes a kinase or phosphotransferase like fold and binds GTP and UTP at its proposed active site. Additionally, using molecular docking this study predicts the binding of five well characterized anti-microbial compounds at the NiRAN domain active site and their drug-likeliness and DFT properties. In line with the current global COVID-19 pandemic urgency, this study provides a new target and potential lead compounds for drug repurposing against SARS-CoV2.

scholarly journals Application of In-Silico Reverse Vaccinology for Designing Multi-Epitope Vaccine Against Coronavirus

2020 ◽  
Author(s):  
Kumar Sharp ◽  
Dr. Shubhangi Dange
Keyword(s):  
Immune Response ◽  
In Silico ◽  
Reverse Vaccinology ◽  
Economic Losses ◽  
The Novel ◽  
Toll Like Receptor ◽  
Ramachandran Plot ◽  
Cell Mediated Immune Response ◽  
Specific Medication ◽  
Novel Coronavirus

In absence of any specific medication or vaccine till now, experimentation has reached new heights. With lockdown imposed in almost every country and huge economic losses the search for a suitable vaccine has still been unsuccessful. In this study we have approached through in-silico method or reverse vaccinology taking advantage of the genome sequence of the novel coronavirus. We created a multi-epitope model vaccine which can elicit both humoral as well as cell-mediated immune response. It is also docked with toll-like receptor 8 TLR-8. The sequence obtained is antigenic, non-allergenic and 86.3% residues are in favourable region of Ramachandran plot. This sequence might have good hope of emerging as the vaccine of the current pandemic if studied more in depth.

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