scholarly journals Insights on cross-species transmission of SARS-CoV-2 from structural modeling

2020 ◽  
Author(s):  
João PGLM Rodrigues ◽  
Susana Barrera-Vilarmau ◽  
João MC Teixeira ◽  
Elizabeth Seckel ◽  
Panagiotis Kastritis ◽  
...  
Keyword(s):  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Protein Interactions ◽  
Animal Species ◽  
Host Protein ◽  
Spike Protein ◽  
Computational Studies ◽  
Wild Animals ◽  
Amino Acid Residues ◽  
Global Pandemic

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 14 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.

scholarly journals Insights on cross-species transmission of SARS-CoV-2 from structural modeling

2020 ◽  
Vol 16 (12) ◽  
pp. e1008449
Author(s):  
João P. G. L. M. Rodrigues ◽  
Susana Barrera-Vilarmau ◽  
João M. C. Teixeira ◽  
Marija Sorokina ◽  
Elizabeth Seckel ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Animal Species ◽  
Host Protein ◽  
Spike Protein ◽  
Computational Studies ◽  
Wild Animals ◽  
Amino Acid Residues ◽  
Susceptible Animal ◽  
Molecular Features ◽  
Global Pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 31 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic and confirmed cases of cross-species transmission, the question of the extent to which this transmission is possible emerges, as well as what molecular features distinguish susceptible from non-susceptible animal species. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also allow us to predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.

ReaxFF-based molecular dynamics simulation of the interaction between plasma ROS and the receptor-binding domain of the spike protein in the capsid protein of SARS-CoV-2

2021 ◽  
Author(s):  
Huichao Wang ◽  
Tong Zhao ◽  
Shuhui Yang ◽  
Liang Zou ◽  
Xiaolong Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Capsid Protein ◽  
Receptor Binding ◽  
Hydrogen Abstraction ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Amino Acid Residues ◽  
Global Epidemic

Abstract Under the severe situation of the current global epidemic, researchers have been working hard to find a reliable way to suppress the infection of the virus and prevent the spread of the epidemic. Studies have shown that the recognition and binding of human angiotensin-converting enzyme 2 (ACE2) by the receptor-binding domain (BRD) of spike protein on the surface of SARS-CoV-2 is a crucial step for SARS-CoV-2 to invade human receptor cells, and blocking this process can inhibit the virus from invading human normal cells. Plasma treatment can disrupt the structure of the RBD and effectively block the binding process. However, the mechanism by which plasma blocks the recognition and binding between the two is not clear. In this study, reaction process between reactive oxygen species (ROS) in plasma and the molecular model of RBD was simulated using a reactive molecular dynamics method. The results showed that the destruction of RBD molecule by ROS was triggered by hydrogen abstraction reactions. O and OH abstracted H atoms from RBD, while the H atoms of H2O2 and HO2 were abstracted by RBD. The hydrogen abstraction resulted in the breakage of C-H, N-H, O-H and C=O bonds and the formation of C=C, C=N bonds. The addition reaction of OH increased the number of O-H bonds and caused the formation of C-O, N-O and O-H bonds. The dissociation of N-H bonds led to the destruction of the original structure of peptide bonds and amino acid residues, change the type of amino acid residues, and caused the conversion of N-C and N=C, C=O and C-O. The simulation partially elucidated the microscopic mechanism of the interaction between ROS in plasma and the capsid protein of SARS-CoV-2, providing theoretical support for the control of SARS-CoV-2 infection by plasma, a contribution to overcoming the global epidemic problem.

scholarly journals Whole-Genome Sequence of SARS-CoV-2 Isolate Siena-1/2020

2020 ◽  
Vol 9 (39) ◽  
Author(s):  
Maria Grazia Cusi ◽  
David Pinzauti ◽  
Claudia Gandolfo ◽  
Gabriele Anichini ◽  
Gianni Pozzi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Genome Sequence ◽  
Amino Acid Change ◽  
Amplicon Sequencing ◽  
Spike Protein ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Nanopore Sequencing ◽  
Protein Coding

ABSTRACT The complete genome sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate Siena-1/2020 was obtained by Nanopore sequencing, combining the direct RNA sequencing and amplicon sequencing approaches. The isolate belongs to the B1.1 lineage, which is prevalent in Europe, and contains a mutation in the spike protein coding sequence leading to the D614G amino acid change.

scholarly journals Peptide recognition and dephosphorylation by the vaccinia VH1 phosphatase

2020 ◽  
Author(s):  
Bryan M. Zhao ◽  
Megan Hogan ◽  
Michael S Lee ◽  
Beverly K. Dyas ◽  
Robert G. Ulrich
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Catalytic Site ◽  
Site Directed Mutagenesis ◽  
Amino Acid Residues ◽  
Protein Protein Interactions ◽  
Host Cell Proteins ◽  
Enzyme Substrate ◽  
Dual Specificity ◽  
Contact Residues

ABSTRACTThe VH1 protein encoded by the highly conserved H1 locus of orthopoxviruses is a dual-specificity phosphatase (DUSPs) that hydrolyzes phosphate groups from phosphorylated tyrosine, serine, and threonine residues of viral and host cell proteins. Because the DUSP activities are required for virus replication, VH1 is a prime target for the development of therapeutic inhibitors. However, the presentation of a shallow catalytic site has thwarted all drug development efforts. As an alternative to direct targeting of catalytic pockets, we describe surface contacts between VH1 and substrates that are essential for full activity and provide a new pathway for developing inhibitors of protein-protein interactions. Critical amino acid residues were manipulated by site-directed mutagenesis of VH1, and perturbation of peptide substrate interactions based on these mutations were assessed by high-throughput assays that employed surface plasmon resonance and phosphatase activities. Two positively-charged residues (Lys-20 and Lys-22) and the hydrophobic side chain of Met-60 appear to orient the polarity of the pTyr peptide on the VH1 surface, while additional amino acid residues that flank the catalytic site contribute to substrate recognition and productive dephosphorylation. We propose that the enzyme-substrate contact residues described here may serve as molecular targets for the development of inhibitors that specifically block VH1 catalytic activity and thus poxvirus replication.

Defining Amino Acid Residues Involved in DNA−Protein Interactions and Revelation of 3‘-Exonuclease Activity in Endonuclease V†

Biochemistry ◽  
2005 ◽  
Vol 44 (34) ◽  
pp. 11486-11495 ◽  
Author(s):  
Hong Feng ◽  
Liang Dong ◽  
Athena M. Klutz ◽  
Nima Aghaebrahim ◽  
Weiguo Cao
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Exonuclease Activity ◽  
Amino Acid Residues ◽  
Endonuclease V ◽  
Dna Protein Interactions

Molecular Cloning of TSARG6 Gene Related to Apoptosis in Human Spermatogenic Cells

2004 ◽  
Vol 36 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Gang Liu ◽  
Guang-Xiu Lu ◽  
Xiao-Wei Xing
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Critical Role ◽  
Human Testis ◽  
Amino Acid Residues ◽  
Spermatogenic Cells ◽  
Protein Protein Interactions ◽  
New Gene ◽  
Pcr Technology ◽  
Dnak Protein

Abstract Beginning from a mouse EST (GenBank accession No. BE644537) which was significantly up-regulated in cryptorchidism and represented a novel gene, we cloned a new gene (GenBank accession No. AY138810) which is related to apoptosis in human spermatogenic cells by means of GeneScan program and PCR technology. The gene whose full cDNA length is 1875 bp containing 8 exons and 7 introns is located in human chromosome 11q13.3. Its protein containing 316 amino acid residues is a new member of HSP40 protein family because the sequence contains the highly conserved J domain which is present in all DnaJ-like proteins and is considered to have a critical role in DnaJ-DnaK protein-protein interactions. TSARG6 protein displays a 45% identity in a 348-amino acid overlap with DJB5_HUMAN protein. The result of RT-PCR and Northern blot analysis showed that TSARG6 is specifically expressed in adult testis and the transcript is 1.8 kb. Based upon all these observations, it is considered that we cloned a new gene which probably inhibited human testis spermatogenesis apoptosis.

scholarly journals Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein

2021 ◽  
Author(s):  
Jan-Philipp Mallm ◽  
Christian Bundschuh ◽  
Heeyoung Kim ◽  
Niklas Weidner ◽  
Simon Steiger ◽  
...  
Keyword(s):  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Type Strain ◽  
Wild Type Strain ◽  
Population Level ◽  
Spike Protein ◽  
Whole Genome ◽  
Wild Type ◽  
Spike Gene ◽  
Mutational Pattern

SummaryVariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are replacing the initial wild-type strain, jeopardizing current efforts to contain the pandemic. Amino acid exchanges in the spike protein are of particular concern as they can render the virus more transmissible or reduce vaccine efficacy. Here, we conducted whole genome sequencing of SARS-CoV-2 positive samples from the Rhine-Neckar district in Germany during January-March 2021. We detected a total of 166 samples positive for a variant with a distinct mutational pattern in the spike gene comprising L18F, L452R, N501Y, A653V, H655Y, D796Y and G1219V with a later gain of A222V. This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. These observations strongly argue for continuous and comprehensive monitoring of SARS-CoV-2 evolution on a population level.

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