scholarly journals Molecular dynamics simulations of the delta and omicron SARS-CoV-2 spike – ACE2 complexes reveal distinct changes between both variants

Author(s):  
Eileen Socher ◽  
Lukas Heger ◽  
Friedrich Paulsen ◽  
Friederike Zunke ◽  
Philipp Arnold

Abstract SARS-CoV-2, the virus which causes the COVID-19 pandemic, changes frequently through the ap-pearance of mutations constantly leading to new variants. However, only few variants evolve as dominating and will be considered as “Variants of Concern” (VOCs) by the world health organization (WHO). At the end of 2020 the alpha (B.1.1.7) variant appeared in the United Kingdom and domi-nated the pandemic situation until mid of 2021 when it was substituted by the delta variant (B.1.617.2) that first appeared in India as predominant variant. At the end of 2021, SARS-CoV-2 omi-cron (B.1.1.529) evolved as the dominating variant. Here, we use in silico modeling and molecular dynamics (MD) simulations of the receptor-binding domain of the viral spike protein and the host cell surface receptor ACE2 to analyze and compare the interaction pattern between the wild type, delta and omicron variants. We identified residue 493 in delta (glutamine) and omicron (arginine) with altered binding properties towards ACE2.

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11590
Author(s):  
Aweke Mulu ◽  
Mulugeta Gajaa ◽  
Haregewoin Bezu Woldekidan ◽  
Jerusalem Fekadu W/mariam

The newly occurred SARS-CoV-2 caused a leading pandemic of coronavirus disease (COVID-19). Up to now it has infected more than one hundred sixty million and killed more than three million people according to 14 May 2021 World Health Organization report. So far, different types of studies have been conducted to develop an anti-viral drug for COVID-19 with no success yet. As part of this, silico were studied to discover and introduce COVID-19 antiviral drugs and results showed that protease inhibitors could be very effective in controlling. This study aims to investigate the binding affinity of three curcumin derived polyphenols against COVID-19 the main protease (Mpro), binding pocket, and identification of important residues for interaction. In this study, molecular modeling, auto-dock coupled with molecular dynamics simulations were performed to analyze the conformational, and stability of COVID-19 binding pocket with diferuloylmethane, demethoxycurcumin, and bisdemethoxycurcumin. All three compounds have shown binding affinity −39, −89 and −169.7, respectively. Demethoxycurcumin and bisdemethoxycurcumin showed an optimum binding affinity with target molecule and these could be one of potential ligands for COVID-19 therapy. And also, COVID-19 main protease binding pocket binds with the interface region by one hydrogen bond. Moreover, the MD simulation parameters indicated that demethoxycurcumin and bisdemethoxycurcumin were stable during the simulation run. These findings can be used as a baseline to develop therapeutics with curcumin derived polyphenols against COVID-19.


Author(s):  
M. Ibrahim Hossain ◽  
Esha Binte Shahriar ◽  
Anamika Sarker ◽  
Nafisa Lubna ◽  
Mehjabeen Haque ◽  
...  

The world is now facing one of the most devastating public health concern where the 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is spreading all over the world initiating from Wuhan, China, started from December, 2019. The World Health Organization (WHO) already announced the situation as pandemic all over the world. According to the webpage of WHO, this SARS-CoV-2 has been spreading all over the world (223 countries, areas or territories) with 126,890,643 of confirmed cases and 2,778,619 of confirmed deaths(as time of March 30, 2021). Accumulated published documents indicate that the SARS-CoV-2 virus primarily affects the lungs causing hypoxia which is the leading cause of death. There are many reports describing that with the progress of this disease, many other organs (such as heart, kidney, liver, brain) of the affected person start to malfunction. Though SARS-CoV-2 uses the cell surface receptor angiotensin-converting enzyme 2 (ACE-2) expressed by lungs, cardiovascular system, kidneys but it is still not clear except lungs all these other organs are directly affected by this virus or not. Therefore, the aim of this review is to gather information about the affected/damaged organs or tissues and the consequences of this damage in the COVID-19 patients.                    Peer Review History: Received 11 March 2021; Revised 8 April; Accepted 23 April, Available online 15 May 2021 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.  Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Vanina Doris Edo’o, University of Yaounde I, Yaounde, Cameroun, [email protected] Idoko Alexander, Caritas University, Enugu, Nigeria, [email protected] Similar Articles: COVID-19: PHARMACOLOGICAL AND THERAPEUTIC APPROACHES USE OF COLCHICINE TO COUNTERACT THE STRONG HYPERINFLAMMATORY STATE INDUCED BY SARS-COV-2 THE RISKS AND ADVANTAGES OF ANTI-DIABETES THERAPY IN THE POSITIVE COVID-19 PATIENT


2019 ◽  
Vol 16 (3) ◽  
pp. 291-300
Author(s):  
Saumya K. Patel ◽  
Mohd Athar ◽  
Prakash C. Jha ◽  
Vijay M. Khedkar ◽  
Yogesh Jasrai ◽  
...  

Background: Combined in-silico and in-vitro approaches were adopted to investigate the antiplasmodial activity of Catharanthus roseus and Tylophora indica plant extracts as well as their isolated components (vinblastine, vincristine and tylophorine). </P><P> Methods: We employed molecular docking to prioritize phytochemicals from a library of 26 compounds against Plasmodium falciparum multidrug-resistance protein 1 (PfMDR1). Furthermore, Molecular Dynamics (MD) simulations were performed for a duration of 10 ns to estimate the dynamical structural integrity of ligand-receptor complexes. </P><P> Results: The retrieved bioactive compounds viz. tylophorine, vinblastin and vincristine were found to exhibit significant interacting behaviour; as validated by in-vitro studies on chloroquine sensitive (3D7) as well as chloroquine resistant (RKL9) strain. Moreover, they also displayed stable trajectory (RMSD, RMSF) and molecular properties with consistent interaction profile in molecular dynamics simulations. </P><P> Conclusion: We anticipate that the retrieved phytochemicals can serve as the potential hits and presented findings would be helpful for the designing of malarial therapeutics.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1711
Author(s):  
Mohamed Ahmed Khaireh ◽  
Marie Angot ◽  
Clara Cilindre ◽  
Gérard Liger-Belair ◽  
David A. Bonhommeau

The diffusion of carbon dioxide (CO2) and ethanol (EtOH) is a fundamental transport process behind the formation and growth of CO2 bubbles in sparkling beverages and the release of organoleptic compounds at the liquid free surface. In the present study, CO2 and EtOH diffusion coefficients are computed from molecular dynamics (MD) simulations and compared with experimental values derived from the Stokes-Einstein (SE) relation on the basis of viscometry experiments and hydrodynamic radii deduced from former nuclear magnetic resonance (NMR) measurements. These diffusion coefficients steadily increase with temperature and decrease as the concentration of ethanol rises. The agreement between theory and experiment is suitable for CO2. Theoretical EtOH diffusion coefficients tend to overestimate slightly experimental values, although the agreement can be improved by changing the hydrodynamic radius used to evaluate experimental diffusion coefficients. This apparent disagreement should not rely on limitations of the MD simulations nor on the approximations made to evaluate theoretical diffusion coefficients. Improvement of the molecular models, as well as additional NMR measurements on sparkling beverages at several temperatures and ethanol concentrations, would help solve this issue.


CrystEngComm ◽  
2021 ◽  
Author(s):  
Andrey Sarikov ◽  
Anna Marzegalli ◽  
Luca Barbisan ◽  
Massimo Zimbone ◽  
Corrado Bongiorno ◽  
...  

In this work, annihilation mechanism of stacking faults (SFs) in epitaxial 3C-SiC layers grown on Si(001) substrates is studied by molecular dynamics (MD) simulations. The evolution of SFs located in...


Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 347
Author(s):  
Wenlin Zhang ◽  
Lingyi Zou

We apply molecular dynamics (MD) simulations to investigate crystal nucleation in incompatible polymer blends under deep supercooling conditions. Simulations of isothermal nucleation are performed for phase-separated blends with different degrees of incompatibility. In weakly segregated blends, slow and incompatible chains in crystallizable polymer domains can significantly hinder the crystal nucleation and growth. When a crystallizable polymer is blended with a more mobile species in interfacial regions, enhanced molecular mobility leads to the fast growth of crystalline order. However, the incubation time remains the same as that in pure samples. By inducing anisotropic alignment near the interfaces of strongly segregated blends, phase separation also promotes crystalline order to grow near interfaces between different polymer domains.


2020 ◽  
Vol 30 (1) ◽  
pp. 38030 ◽  
Author(s):  
Deivendran Kalirathinam ◽  
Raj Guruchandran ◽  
Prabhakar Subramani

The 2019 novel coronavirus officially named as coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization, has spread to more than 180 countries. The ongoing global pandemic of severe acute respiratory syndrome coronavirus, which causes COVID-19, spread to the United Kingdom (UK) in January 2020. Transmission within the UK was confirmed in February, leading to an epidemic with a rapid increase in cases in March. As on April 25- 2020, there have been 148,377 confirmed cases of COVID-19 in the UK and 20,319 people with confirmed infection have died. Survival of critically ill patients is frequently associated with significant functional impairment and reduced health-related quality of life. Early physiotherapy and community rehabilitation of COVID-19 patients has recently been identified as an essential therapeutic tool and has become a crucial evidence-based component in the management of these patients. This comprehensive narrative review aims to describe recent progress in the application of physiotherapy management in COVID 19 patients. Assessment and evidence- based treatment of these patients should include prevention, reduction of adverse consequences in immobilization, and long-term impairment sequelae. A variety of techniques and modalities of early physiotherapy in intensive care unit are suggested by clinical research. They should be applied according to the stage of the disease, comorbidities, and patient’s level of cooperation.


2016 ◽  
Vol 18 (37) ◽  
pp. 25806-25816 ◽  
Author(s):  
Carlos Navarro-Retamal ◽  
Anne Bremer ◽  
Jans Alzate-Morales ◽  
Julio Caballero ◽  
Dirk K. Hincha ◽  
...  

Unfolding of intrinsically unstructured full-length LEA proteins in a differentially crowded environment can be modeled by 30 ns MD simulations in accordance with experimental data.


Symmetry ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1259
Author(s):  
Maksymilian Dziura ◽  
Basel Mansour ◽  
Mitchell DiPasquale ◽  
P. Charukeshi Chandrasekera ◽  
James W. Gauld ◽  
...  

In this review, we delve into the topic of the pulmonary surfactant (PS) system, which is present in the respiratory system. The total composition of the PS has been presented and explored, from the types of cells involved in its synthesis and secretion, down to the specific building blocks used, such as the various lipid and protein components. The lipid and protein composition varies across species and between individuals, but ultimately produces a PS monolayer with the same role. As such, the composition has been investigated for the ways in which it imposes function and confers peculiar biophysical characteristics to the system as a whole. Moreover, a couple of theories/models that are associated with the functions of PS have been addressed. Finally, molecular dynamic (MD) simulations of pulmonary surfactant have been emphasized to not only showcase various group’s findings, but also to demonstrate the validity and importance that MD simulations can have in future research exploring the PS monolayer system.


2005 ◽  
Vol 1 (4) ◽  
pp. 204-209
Author(s):  
O.B. Malcıoğlu ◽  
Ş. Erkoç

The minimum energy structures of CmTin microclusters and nanoparticles have been investigated theoretically by performing molecular–dynamics (MD) simulations. Selected crystalline and completely random initial geometries are considered. The potential energy function (PEF) used in the calculations includes two– and three–body atomic interactions for C-Ti binary systems. Molecular–dynamics simulations have been performed at 1 K and 300 K. It has been found that initial geometry has a very strong influence on relaxed geometry


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