scholarly journals Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

2020 ◽  
Author(s):  
Ashish Patel ◽  
Malathi Rajendran ◽  
Suresh B Pakala ◽  
Ashish Shah ◽  
Harnisha Patel ◽  
...  
Keyword(s):  
Binding Energy ◽  
Viral Entry ◽  
Curcuma Longa ◽  
Docking Studies ◽  
Binding Energies ◽  
Surface Glycoprotein ◽  
Spike Protein ◽  
Pharmacokinetic Parameters ◽  
Angiotensin Converting Enzyme 2 ◽  
Potential Inhibitors

COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74 % identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle. Potential inhibitors of SARS-CoV and SARS-CoV-2 Spike proteins was determined using molecular docking studies. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry. The curcumin and its derivatives displayed binding energies, ΔG, ranging from -14.18 to -4.04 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J). The least binding energy was seen in bis-desmethoxycurcumin with: ΔG = -14.18 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors.<br>

scholarly journals Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

2020 ◽  
Author(s):  
Ashish Patel ◽  
Malathi Rajendran ◽  
Suresh B Pakala ◽  
Ashish Shah ◽  
Harnisha Patel ◽  
...  
Keyword(s):  
Binding Energy ◽  
Viral Entry ◽  
Curcuma Longa ◽  
Binding Energies ◽  
Surface Glycoprotein ◽  
Spike Protein ◽  
Pharmacokinetic Parameters ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Entry Inhibitors

COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74 % identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle. The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J: Receptor binding domain, RBD) was used to determine potential small molecule inhibitors. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry. The curcumin and its derivatives displayed binding energies, ΔG, ranging from -10.98 to -5.12 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J). The least binding energy was seen in bis-demethoxycurcumin with: ΔG = -10.98 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors. However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.<br>

scholarly journals Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

2020 ◽  
Author(s):  
Ashish Patel ◽  
Malathi Rajendran ◽  
Suresh B Pakala ◽  
Ashish Shah ◽  
Harnisha Patel ◽  
...  
Keyword(s):  
Binding Energy ◽  
Viral Entry ◽  
Curcuma Longa ◽  
Binding Energies ◽  
Surface Glycoprotein ◽  
Spike Protein ◽  
Pharmacokinetic Parameters ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Entry Inhibitors

COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74 % identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle. The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J: Receptor binding domain, RBD) was used to determine potential small molecule inhibitors. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry. The curcumin and its derivatives displayed binding energies, ΔG, ranging from -10.98 to -5.12 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J). The least binding energy was seen in bis-demethoxycurcumin with: ΔG = -10.98 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors. However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.<br>

Molecular modeling and docking calculations of 4-acyloxy-biphenyl-4′-N-butylcarbamates as potential inhibitors of human butyrylcholinesterase

2016 ◽  
Vol 94 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Yu-Fang Shen ◽  
Gan-Hong Chen ◽  
Shu-Hsien Lin ◽  
Gialih Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Binding Energy ◽  
Linear Correlation ◽  
Kinetic Studies ◽  
Docking Studies ◽  
Binding Energies ◽  
Binding Modes ◽  
Docking Calculations ◽  
Potential Inhibitors

The kinetic studies and drug designs of butyrylcholinesterase play an important role in the development of Alzheimer’s disease therapeutics. In this research, automated docking studies were performed to provide useful insights into butyrylcholinesterase inhibition binding modes with designed 4-acyloxy-biphenyl-4′-N-butylcarbamates (compounds 1–8). Moreover, several significant linear correlations between experimental and calculated docking results are observed. Among compounds 1–7, compound 3, which exhibits the strongest hydrophobicity and has four carbonyl hydrogen bindings, shows the highest binding affinity (Ki = 1.4 μmol/L) with a binding energy of −7.99 kcal/mol. The observed linear correlation of experimental and calculated inhibition constants (Ki) indicates that the molecular docking results are reliable. Moreover, a good linear correlation is observed between calculated binding energies and experimental pKi. The experimental Hansch hydrophobicity constants (π values) are also correlated with the docked binding energy. This study reveals important correlations between butyrylcholinesterase experimental and docking results that contribute to the kinetic based identification of antagonists for the treatment of Alzheimer’s disease. Furthermore, these docked models provide important insights into a potential series of 4,4′-biphenol-based inhibitors of butyrylcholinesterase.

Molecular Docking Studies for Protein-Targeted Drug Development in SARS-CoV-2

2021 ◽  
Vol 18 ◽  
Author(s):  
Ahmad Dzulfikri Nurhan ◽  
Maria Apriliani Gani ◽  
Saipul Maulana ◽  
Siswandono Siswandono ◽  
Chrismawan Ardianto ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Docking Studies ◽  
Binding Energies ◽  
Spike Glycoprotein ◽  
Protein Targets ◽  
Lipinski’S Rule ◽  
Global Pandemic ◽  
Potential Inhibitors ◽  
3Cl Protease

Background: The SARS-CoV-2/COVID-19 infection has resulted in a global pandemic and emergency. Currently, there is no therapeutic agent that has been proven to be effective and selective to deal with this pandemic. Objective: In this study, we explored and screened 401 compounds-related viruses that may inhibit one or more of the three protein targets in SARS-CoV-2 (3CL protease, RdRp, and spike glycoprotein) using in-silico approach. Methods: Lipinski's rule of five was used as an initial screening for these compounds. Ligand preparation was carried out using JChem software and Schrödinger's LigPrep module, while protein elucidation used AutoDockTools-1.5.6. Molecular docking was analyzed using AutoDockVina. Results: A total of five compounds-related viruses were obtained from each SARS-CoV-2 protein with ideal and potential binding energy as a candidate for target protein inhibitor on SARS-CoV-2. At the protein 3CL protease imatinib, TAK-981, lopinavir, mefloquine, and sitagliptin were found to be potential inhibitors of this protein. In the protein RdRp tetrandrine, relacatib, AZD7986, imatinib, and TAK-981 revealed potential as an inhibitor of this protein. At the protein spike, glycoprotein AZD7986, selinexor, imatinib, lopinavir, and ciclesonide, were found to have potential as inhibitors of these proteins. All these compounds have better binding energy than the three comparator drugs (remdesivir, chloroquine, and hydroxychloroquine). Conclusion: We have obtained several compounds-related viruses with reliable binding energies to the SARS-CoV-2 proteins and potentially better than the three comparator drugs. Furthermore, this research will pave the way for accelerating the development of Covid-19 drugs.

scholarly journals The Effects of Aβ1-42 Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2

2021 ◽  
Vol 22 (15) ◽  
pp. 8226
Author(s):  
John Tsu-An Hsu ◽  
Chih-Feng Tien ◽  
Guann-Yi Yu ◽  
Santai Shen ◽  
Yi-Hsuan Lee ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Viral Entry ◽  
Negative Impact ◽  
Spike Protein ◽  
Infection Model ◽  
Converting Enzyme ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
People With Dementia ◽  
The Impact

Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer’s disease (AD), the major form of dementia, β-amyloid (Aβ) levels in the blood are increased; however, the impact of elevated Aβ levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aβ1-42, but not Aβ1-40, bound to various viral proteins with a preferentially high affinity for the spike protein S1 subunit (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the viral receptor, angiotensin-converting enzyme 2 (ACE2). These bindings were mainly through the C-terminal residues of Aβ1-42. Furthermore, Aβ1-42 strengthened the binding of the S1 of SARS-CoV-2 to ACE2 and increased the viral entry and production of IL-6 in a SARS-CoV-2 pseudovirus infection model. Intriguingly, data from a surrogate mouse model with intravenous inoculation of Aβ1-42 show that the clearance of Aβ1-42 in the blood was dampened in the presence of the extracellular domain of the spike protein trimers of SARS-CoV-2, whose effects can be prevented by a novel anti-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ1-42 to the S1 of SARS-CoV-2 and ACE2 may have a negative impact on the course and severity of SARS-CoV-2 infection. Further investigations are warranted to elucidate the underlying mechanisms and examine whether reducing the level of Aβ1-42 in the blood is beneficial to the fight against COVID-19 and AD.

scholarly journals Combinatorial Library Designing and Virtual Screening of Cryptolepine Derivatives against Topoisomerase II by Molecular Docking

2020 ◽  
Author(s):  
Maria ◽  
Zahid Khan
Keyword(s):  
Molecular Docking ◽  
Cell Division ◽  
Binding Energy ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Combinatorial Library ◽  
Topoisomerase Ii ◽  
Computational Study ◽  
Binding Energies ◽  
Potential Inhibitors

AbstractComputational approaches have emerging role for designing potential inhibitors against topoisomerase 2 for treatment of cancer. TOP2A plays a key role in DNA replication before cell division and thus facilitates the growth of cells. This function of TOP2A can be suppressed by targeting with potential inhibitors in cancer cells to stop the uncontrolled cell division. Among potential inhibitors cryptolepine is more selective and has the ability to intercalate into DNA, effectively block TOP2A and cease cell division in cancer cells. However, cryptolepine is non-specific and have low affinity, therefore, a combinatorial library was designed and virtually screened for identification of its derivatives with greater TOP2A binding affinities.A combinatorial library of 31114 derivatives of cryptolepine was formed and the library was virtually screened by molecular docking to predict the molecular interactions between cryptolepine derivatives and TOP2A taking cryptolepine as standard. The overall screening and docking approach explored all the binding poses of cryptolepine for TOP2A to calculate binding energy. The compounds are given database number 8618, 907, 147, 16755, and 8186 scored lowest binding energies of −9.88kcal/mol, −9.76kcal/mol, −9.75kcal/mol, −9.73kcal/mol, and −9.72kcal/mol respectively and highest binding affinity while cryptolepine binding energy is −6.09kcal/mol. The good binding interactions of the derivatives showed that they can be used as potent TOP2A inhibitors and act as more effective anticancer agents than cryptolepine itself. The interactions of derivatives with different amino acid residues were also observed. A comprehensive understanding of the interactions of proposed derivatives with TOP2A helped for searching more novel and potent drug-like molecules for anticancer therapy. This Computational study suggests useful references to understand inhibition mechanisms that will help in the modification of TOP2A inhibitors.

scholarly journals MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE

2020 ◽  
pp. 174-178
Author(s):  
SHAILENDRA SANJAY SURYAWANSHI ◽  
POOJA BHAVAKANA JAYANNACHE ◽  
RAJKUMAR SANJAY PATIL ◽  
PALLED MS ◽  
ALEGAON SG
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Studies ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Main Protease ◽  
Potential Inhibitors ◽  
Binding Energy Calculations ◽  
Native Ligand

Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease.

scholarly journals Cell-Mimicking Nanodecoys Protect Lung Cells by Neutralization of SARS-CoV-2 Spike Proteins

2020 ◽  
Author(s):  
Zhenhua Li ◽  
Phuong-Uyen C. Dinh ◽  
Kristen D. Popowski ◽  
Halle Lutz ◽  
Zhenzhen Wang ◽  
...  
Keyword(s):  
Viral Entry ◽  
Human Lung ◽  
Spike Protein ◽  
Inhalation Therapy ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Non Invasive ◽  
Global Pandemic ◽  
Integral Role

Abstract Coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has grown into a global pandemic, with no specific antiviral treatments or vaccines are yet approved. The viral receptor, angiotensin-converting enzyme 2 (ACE2), has been demonstrated to play an integral role in the pathogenesis of SARS-CoV-2, necessary for host cell viral entry. Inspired by this, we synthesized ACE2 nanodecoys from human lung spheroid cells (LSCs) capable of binding the Spike protein as a potential neutralization agent for SARS-CoV-2. Our results show LSC-nanodecoys has a high affinity and neutralization efficiency to both spike protein and chemically synthesized SARS-CoV-2 mimics. In addition, non-invasive inhalation therapy in mice showed successful delivery of the nanodecoy to the lungs, as well as in-vivo retention of the nanodecoys over 72 hours after a single administration. Furthermore, inhalation of nanodecoy accelerated the clearance of SARS-CoV-2 mimics from the lung and did not cause toxicity.

scholarly journals Evaluation of Yashtimadhu (Glycyrrhiza glabra) active Phytochemicals Against Novel Coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Dharmendra Kumar Maurya
Keyword(s):  
Viral Entry ◽  
Virus Disease ◽  
Scientific Basis ◽  
Docking Studies ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Protease ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract Corona Virus Disease 2019 (COVID-19) caused by a novel coronavirus emerged from Wuhan, China in December 2019. It has spread to more than 205 countries and become pandemic now. Currently, there are no FDA approved drugs or vaccines available and hence several studies are going on in search of suitable drug that can target viral proteins or host receptor for the prevention and management of COVID-19. The search for plant-based anti-viral agents against the SARS-CoV-2 is promising because several of plants have been shown to possess anti-viral activities against different viruses. Here, we used molecular docking approach to explore the use of Indian Ayurvedic herbs, Yashtimadhu in prevention and management of COVID-19. In the present study we have evaluated the effectiveness of phytochemicals found in Yashtimadhu against Main Protease (Mpro), Spike (S) protein and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 (ACE2) receptor and furin protease. Apart from this, we have also performed in-silico drug-likeness and predicted pharmacokinetics of the selected phytochemicals found in the Yashtimadhu. Our study shows that several phytochemicals found in this plant have potential to bind with important proteins of SARS-CoV-2 which are essential for viral infection and replication. Overall our study provides scientific basis in terms of binding of active ingredients present in Yashtimadhu with SARS-CoV-2 target proteins. Our docking studies reveal that Yashtimadhu may inhibit the viral severity by interfering with viral entry as well as its multiplication in the infected persons. Thus Yashtimadhu may be helpful in the prevention and management of the COVID-19.

scholarly journals A SARS-CoV-2 serological assay to determine the presence of blocking antibodies that compete for human ACE2 binding

2020 ◽  
Author(s):  
James R. Byrnes ◽  
Xin X. Zhou ◽  
Irene Lui ◽  
Susanna K. Elledge ◽  
Jeff E. Glasgow ◽  
...  
Keyword(s):  
Viral Entry ◽  
Humoral Response ◽  
Spike Protein ◽  
Block Interaction ◽  
Serological Assay ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Receptor ◽  
Neutralizing Capacity ◽  
High Throughput Method ◽  
Blocking Antibodies

ABSTRACTAs SARS-CoV-2 continues to spread around the world, there is an urgent need for new assay formats to characterize the humoral response to infection. Convalescent serum is being used for treatment and for isolation of patient-derived antibodies. However, currently there is not a simple means to estimate serum bulk neutralizing capability. Here we present an efficient competitive serological assay that can simultaneously determine an individual’s seropositivity against the SARS-CoV-2 Spike protein and estimate the neutralizing capacity of anti-Spike antibodies to block interaction with the human angiotensin converting enzyme 2 (ACE2) required for viral entry. In this ELISA-based assay, we present natively-folded viral Spike protein receptor binding domain (RBD)-containing antigens via avidin-biotin interactions. Sera are then supplemented with soluble ACE2-Fc to compete for RBD-binding serum antibodies, and antibody binding quantified. Comparison of signal from untreated serum and ACE2-Fc-treated serum reveals the presence of antibodies that compete with ACE2 for RBD binding, as evidenced by loss of signal with ACE2-Fc treatment. In our test cohort of nine convalescent SARS-CoV-2 patients, we found all patients had developed anti-RBD antibodies targeting the epitope responsible for ACE2 engagement. This assay provides a simple and high-throughput method to screen patient sera for potentially neutralizing anti-Spike antibodies to enable identification of candidate sera for therapeutic use.

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