scholarly journals Structural basis for receptor recognition by the novel coronavirus from Wuhan

2020 ◽  
Author(s):  
Jian Shang ◽  
Gang Ye ◽  
Ke Shi ◽  
Yushun Wan ◽  
Chuming Luo ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Intervention Strategies ◽  
Structural Basis ◽  
The Novel ◽  
Recognition Mechanism ◽  
Future Evolution ◽  
Receptor Recognition ◽  
Novel Coronavirus

Abstract A novel SARS-like coronavirus (2019-nCoV) recently emerged from Wuhan, China and is quickly spreading in humans. A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infection, pathogenesis, and host range. 2019-nCoV and SARS-CoV recognize the same host receptor ACE2. Here we determined the crystal structure of 2019-nCoV receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex of human ACE2.Compared with SARS-CoV, an ACE2-binding ridge in 2019-nCoV RBD takes more compact conformations, causing structural changes at the RBD/ACE2 interface. Adaptive to these structural changes, several mutations in 2019-nCoV RBD enhance ACE2- binding affinity, contributing to the high infectivity of 2019-CoV. These mutations also reveal the molecular mechanisms of the animal-to-human transmission of 2019-nCoV. Alarmingly, a single N439R mutation in 2019-nCoV RBD further enhances its ACE2- binding affinity, indicating possible future evolution of 2019-nCoV in humans. This study sheds light on the epidemiology and evolution of 2019-nCoV, and provides guidance for intervention strategies targeting receptor recognition by 2019-nCoV.

scholarly journals SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development

2020 ◽  
Vol 10 ◽  
Author(s):  
Mei-Yue Wang ◽  
Rong Zhao ◽  
Li-Juan Gao ◽  
Xue-Fei Gao ◽  
De-Ping Wang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Protein Structures ◽  
The Novel ◽  
Recognition Mechanism ◽  
Antiviral Compounds ◽  
The World ◽  
Receptor Recognition ◽  
Epidemiological Characteristics ◽  
Therapeutics Development

The pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing great threats to the world in many aspects. Effective therapeutic and preventive approaches including drugs and vaccines are still unavailable although they are in development. Comprehensive understandings on the life logic of SARS-CoV-2 and the interaction of the virus with hosts are fundamentally important in the fight against SARS-CoV-2. In this review, we briefly summarized the current advances in SARS-CoV-2 research, including the epidemic situation and epidemiological characteristics of the caused disease COVID-19. We further discussed the biology of SARS-CoV-2, including the origin, evolution, and receptor recognition mechanism of SARS-CoV-2. And particularly, we introduced the protein structures of SARS-CoV-2 and structure-based therapeutics development including antibodies, antiviral compounds, and vaccines, and indicated the limitations and perspectives of SARS-CoV-2 research. We wish the information provided by this review may be helpful to the global battle against SARS-CoV-2 infection.

Online Synchronous Teaching during a Pandemic

2022 ◽  
Vol 17 (6) ◽  
pp. 0-0
Keyword(s):  
Online Learning ◽  
Structural Changes ◽  
Private University ◽  
Educational Institutions ◽  
The Novel ◽  
Educational Transformation ◽  
Online Mode ◽  
Novel Coronavirus ◽  
The University ◽  
Depth Interviews

As the novel Coronavirus (COVID-19) spread rapidly across the globe, most educational institutions tried to address major challenges of engaging students in a productive way and disseminating knowledge through online learning. Given this consideration, the present study qualitatively explores the observations and experiences of a private university and giant strides taken by the institution in adapting and delivering value to all the stakeholders through educational transformation during the pandemic. The data was collected using observations and in depth interviews. The findings of the study revealed that the university went through certain structural changes and modified teaching pedagogy for virtual delivery like providing support and training to the faculty before shifting completely to online mode and delivering the sessions online in both synchronous and asynchronous mode. The results of the study are likely to help transform and address the major challenges of engaging students in a productive way and disseminating knowledge through online learning during a pandemic.

Structural basis for designing an array of engrailed homeodomains

2020 ◽  
Vol 76 (9) ◽  
pp. 824-833
Author(s):  
Tomoko Sunami ◽  
Yu Hirano ◽  
Taro Tamada ◽  
Hidetoshi Kono
Keyword(s):  
Dna Binding ◽  
Binding Affinity ◽  
Binding Activity ◽  
Structural Basis ◽  
Target Sequence ◽  
Specific Interactions ◽  
Wild Type ◽  
Recognition Mechanism ◽  
Target Sites ◽  
The Individual

Small DNA-binding proteins that target desired sequences have the potential to act as a scaffold for molecular tools such as genome editing. In this study, an engrailed homeodomain (EHD) was chosen and it was evaluated whether it could be used as a molecular module that can connect to itself to recognize a longer target sequence. It was previously shown that two EHDs connected by a linker (EHD2) recognize a target sequence twice as long as that recognized by a single EHD in cells only when Arg53 in each EHD in the tandem protein is mutated to alanine {(EHD[R53A])2}. To investigate the recognition mechanism of (EHD[R53A])2, the crystal structure of the (EHD[R53A])2–DNA complex was determined at 1.6 Å resolution. The individual EHDs were found to adopt the typical homeodomain fold. Most importantly, the base-specific interactions in the major groove necessary for the affinity/specificity of wild-type EHD were preserved in (EHD[R53A])2. Bacterial assays confirmed that the base-specific interactions are retained under cellular conditions. These observations indicate that the R53A mutation only causes a loss of the arginine–phosphate interaction at the protein–DNA interface, which reduces the DNA-binding affinity compared with the wild type. It is therefore concluded that (EHD[R53A])2 precisely recognizes tandem target sites within cells, enabling the individual EHDs to concurrently bind to the target sites with modest binding affinity. This suggests that modulation of the binding activity of each EHD is vital to construct a protein array that can precisely recognize a sequence with multiple target sites.

scholarly journals Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic

2020 ◽  
Vol 146 ◽  
pp. 111805
Author(s):  
Dimitrios Vlachakis ◽  
Eleni Papakonstantinou ◽  
Thanasis Mitsis ◽  
Katerina Pierouli ◽  
Io Diakou ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
The Novel ◽  
Pharmacological Targets ◽  
Novel Coronavirus

scholarly journals Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

2020 ◽  
Author(s):  
Jinsung Yang ◽  
Simon Petitjean ◽  
Sylvie Derclaye ◽  
Melanie Koehler ◽  
Qingrong Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Binding Pocket ◽  
Host Cells ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Force Microscopy ◽  
Binding Interface ◽  
Atomic Force ◽  
Viral Glycoproteins ◽  
Novel Coronavirus

Abstract Study of virus entry into cells is of critical importance for a better understanding of the interactions established between the viral glycoproteins and their receptors at the cell surface and could help to develop novel antiviral strategies. The novel coronavirus (SARS-CoV-2) entry into host cells is mediated by the transmembrane spike glycoprotein (S-glycoprotein) and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we used atomic force microscopy to investigate the molecular mechanisms by which the S- glycoprotein binds to the ACE2 receptor. We demonstrated, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as a binding interface within the S- glycoprotein with the ACE2 receptor and we extracted the kinetic and thermodynamic properties of this binding pocket. Altogether, these results give a dynamic picture of the established interaction in physiologically relevant conditions. Finally, we identified and tested several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

scholarly journals Achieving Effective Treatment Goals against New Coronavirus (SARS-CoV-2) by Identifying the Molecular Details of the Virus Genome

2021 ◽  
Author(s):  
Khalil Khashei Varnamkhasti ◽  
Marzieh Alipour ◽  
Siros Naeimi
Keyword(s):  
Effective Treatment ◽  
Genomic Organization ◽  
Cost Effective ◽  
Virus Genome ◽  
Treatment Goals ◽  
The Novel ◽  
Future Evolution ◽  
Global Epidemic ◽  
Cost Effective Treatment ◽  
Novel Coronavirus

Introduction: We are currently faced with a global epidemic of a new coronavirus (SARS-CoV-2) that It affects not only thousands of people in China, but all over the world. The rapid increase in cases appears to be related to the active genome of the virus, which may affect its pathogenesis. An understanding of the novel coronavirus genomic organization will help us in understanding their origins and likely course of future evolution and identify novel cost-effective treatment.

scholarly journals In Silico Identification of Potent COVID-19 Main Protease Inhibitors from FDA Approved Antiviral Compounds and Active Phytochemicals through Molecular Docking: A Drug Repurposing Approach

2020 ◽  
Author(s):  
Vaishali Chandel ◽  
Sibi Raj ◽  
Brijesh Rathi ◽  
Dhruv Kumar
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Binding Affinity ◽  
Drug Repurposing ◽  
The Novel ◽  
Antiviral Compounds ◽  
Ssrna Virus ◽  
Main Protease ◽  
Adme Properties ◽  
Novel Coronavirus

The Novel Coronavirus (COVID-19) is a positive-sense single-stranded RNA ((+)ssRNA) virus. The COVID-19 Main Proteases play very important role in the propagation of the Novel Coronavirus (COVID-19). It has already killed more than 8000 people around the world and thousands of people are getting infected every day. Therefore, it is very important to identify a potential inhibitor against COVID-19 Main Proteases to inhibit the propagation of the Novel Coronavirus (COVID-19). We have applied a drug repurposing approach of computational methodology, depending on the synergy of molecular docking and virtual screening techniques, aimed to identify possible potent inhibitors against Novel Coronavirus (COVID-19) from FDA approved antiviral compounds and from the library of active phytochemicals. On the basis of recently resolved COVID-19 Main Protease crystal structure (PDB:6LU7), the library of 100 FDA approved antiviral compounds and 1000 active components of Indian Medicinal Plants extracted for screening against COVID-19 Main Protease. The compounds were further screened using Pyrex virtual screening tool and then best inhibitors, top 19 compounds optimally docked to the COVID-19 Main Protease structure to understand the participation of specific amino acids with inhibitors at active sites. Total 19 best compounds were identified after screening based on their highest binding affinity with respect to the other screened compounds. Out of 19, 6 best compounds were further screened based on their binding affinity and best ADME properties. Nelfinavir exhibited highest binding energy -8.4 kcal/mol and strong stability with the TRP207, ILE281, LEU282, PHE3, PHE291, GLN127, ARG4, GLY283, GLU288, LYS5, LYS137, TYR126, GLY138, TYR126, SER139 and VAL135 amino acid residues of COVID-19 Main Protease participating in the interaction at the binding pocket. In addition to Nelfinavir (-8.4), Rhein (-8.1), Withanolide D (-7.8), Withaferin A (-7.7), Enoxacin (-7.4), and Aloe-emodin (-7.4) also showed good binding affinity and best ADME properties. Our findings suggest that these compounds can be used as potential inhibitors against COVID-19 Main Protease, which could be helpful in inhibiting the propagation of the Novel Coronavirus (COVID-19). Moreover, further in vitro and in vivo validation of these findings would be very helpful to bring these inhibitors to next level study.

scholarly journals Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection

2020 ◽  
pp. 107385842095690 ◽  
Author(s):  
Rafal Butowt ◽  
Christopher S. von Bartheld
Keyword(s):  
Olfactory Epithelium ◽  
Molecular Mechanisms ◽  
Large Fraction ◽  
Current Evidence ◽  
The Novel ◽  
Brain Infection ◽  
Sustentacular Cells ◽  
Underlying Mechanisms ◽  
Novel Coronavirus ◽  
Taste Dysfunction

In recent months it has emerged that the novel coronavirus—responsible for the COVID-19 pandemic—causes reduction of smell and taste in a large fraction of patients. The chemosensory deficits are often the earliest, and sometimes the only signs in otherwise asymptomatic carriers of the SARS-CoV-2 virus. The reasons for the surprisingly early and specific chemosensory dysfunction in COVID-19 are now beginning to be elucidated. In this hypothesis review, we discuss implications of the recent finding that the prevalence of smell and taste dysfunction in COVID-19 patients differs between populations, possibly because of differences in the spike protein of different virus strains or because of differences in the host proteins that enable virus entry, thus modifying infectivity. We review recent progress in defining underlying cellular and molecular mechanisms of the virus-induced anosmia, with a focus on the emerging crucial role of sustentacular cells in the olfactory epithelium. We critically examine the current evidence whether and how the SARS-CoV-2 virus can follow a route from the olfactory epithelium in the nose to the brain to achieve brain infection, and we discuss the prospects for using the smell and taste dysfunctions seen in COVID-19 as an early and rapid diagnostic screening tool.

scholarly journals Assessing potential inhibitors of SARS-CoV-2 main protease from available drugs using free energy perturbation simulations

RSC Advances ◽  
2020 ◽  
Vol 10 (66) ◽  
pp. 40284-40290
Author(s):  
Son Tung Ngo ◽  
Hung Minh Nguyen ◽  
Le Thi Thuy Huong ◽  
Pham Minh Quan ◽  
Vi Khanh Truong ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Affinity ◽  
Free Energy Perturbation ◽  
The Novel ◽  
Main Protease ◽  
Energy Perturbation ◽  
Novel Coronavirus ◽  
Potential Inhibitors

Free Energy Pertubation (FEP) can be used to accurately predict the binding affinity of a ligand to the main protease (Mpro) of the novel coronavirus SARS-CoV-2.

scholarly journals The Molecular Basis of Gender Variations in Mortality Rates Associated With the Novel Coronavirus (COVID-19) Outbreak

2021 ◽  
Vol 8 ◽  
Author(s):  
Ibrahim Y. Hachim ◽  
Mahmood Y. Hachim ◽  
Iman Mamdouh Talaat ◽  
Vanessa M. López-Ozuna ◽  
Narjes Saheb Sharif-Askari ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Mortality Rates ◽  
Pathway Enrichment Analysis ◽  
The Novel ◽  
Differential Outcomes ◽  
Novel Coronavirus ◽  
Gender Variations ◽  
Epidemiological Characteristics

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact among different subpopulations. Emerging evidence from different parts of the world showed that male patients usually had a longer disease course as well as worse outcome compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for more effective and personalized response to this disease outbreak. For that reason, here we investigate the molecular basis of gender variations in mortality rates related to COVID-19 infection. To achieve this, we used publicly available lung transcriptomic data from 141 females and compare it to 286 male lung tissues. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Further analysis using pathway enrichment analysis revealed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (CHM, DDX3X, FGFR3, SFRP2, and NLRP2) in males lungs compared to females. This pathway is believed to be essential for immune response and antimicrobial activity in the lung tissues. In contrast, our results showed an increased upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation in male lungs compared to females. Finally, our results showed a differential expression of genes involved in the immune response including the NLRP2 and PTGDR2 in lung tissues of both genders, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed in both genders during the COVID-19 outbreak. This maybe essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

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