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.

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 Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

2020 ◽  
Author(s):  
Houcemeddine Othman ◽  
Zied Bouslama ◽  
Jean-Tristan Brandenburg ◽  
Jorge da Rocha ◽  
Yosr Hamdi ◽  
...  
Keyword(s):  
Hot Spot ◽  
Evolutionary Process ◽  
Cell Receptor ◽  
Host Protein ◽  
Spike Protein ◽  
Amino Acid Residues ◽  
Binding Assays ◽  
Angiotensin Converting Enzyme 2 ◽  
The Stability ◽  
The Impact

AbstractThe spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.

scholarly journals Semi-quantitative risk assessment of peste des petits ruminants introduction with wild animals into Russian Federation

2021 ◽  
pp. 277-284
Author(s):  
S. V. Shcherbinin ◽  
F. I. Korennoy ◽  
T. P. Akimova ◽  
A. K. Karaulov
Keyword(s):  
Russian Federation ◽  
Animal Species ◽  
Small Ruminant ◽  
Small Ruminants ◽  
Quantitative Risk Assessment ◽  
Disease Spread ◽  
Wild Animals ◽  
Susceptible Animal ◽  
Animal Populations ◽  
The Russian Federation

The Russian Federation was officially recognized free from peste des petitts ruminants (PPR). As far as the disease infects both domestic and wild small ruminants, it is important to identify the level of the threat associated with the wild fauna diversity in the neighboring countries, where PPR outbreaks were reported. For that reason, habitats of various disease susceptible animal species were examined. Habitats of the wild susceptible animals were mapped for further examination of the interactions between different animal species using zoological research data; PPR outbreaks in wild animals were also designated in the map thus allowing for the detection of the potential routes of the infection spread in the population and introduction to the country. Analysis of the PPR epidemic situation in the country demonstrated that the disease cases were reported in wild mountain animals (ibices and moufflons) and migratory steppe animals (gazelles and saigas). Risk of this highly contagious viral disease spread in wild small ruminants in Mongolia was reported (probability 0.77). Expert survey was carried out for the determination of possible trends and factors of the infection introduction with the wild susceptible animals, through which small ruminant epizootologists assessed the risk probability. During the survey it was determined that PPR was expected to be introduced from Mongolia (probability 0.81), and of major significance were seasonal migrations of wild animal populations. The resulted semi-quantitative parameters of the potential risk can be recommended for the arrangement and implementation of measures aimed at prevention of PPR introduction and spread in the intact domestic and wild small ruminant populations inhabiting the territory of the Russian Federation.

scholarly journals Current Status of Putative Animal Sources of SARS-CoV-2 Infection in Humans: Wildlife, Domestic Animals and Pets

2021 ◽  
Vol 9 (4) ◽  
pp. 868
Author(s):  
Max Maurin ◽  
Florence Fenollar ◽  
Oleg Mediannikov ◽  
Bernard Davoust ◽  
Christian Devaux ◽  
...  
Keyword(s):  
Animal Species ◽  
Biological Properties ◽  
Experimental Models ◽  
Current Data ◽  
The Body ◽  
Receptor Expression ◽  
Current Status ◽  
Susceptible Animal

SARS-CoV-2 is currently considered to have emerged from a bat coronavirus reservoir. However, the real natural cycle of this virus remains to be elucidated. Moreover, the COVID-19 pandemic has led to novel opportunities for SARS-CoV-2 transmission between humans and susceptible animal species. In silico and in vitro evaluation of the interactions between the SARS-CoV-2 spike protein and eucaryotic angiotensin-converting enzyme 2 (ACE2) receptor have tentatively predicted susceptibility to SARS-CoV-2 infection of several animal species. Although useful, these data do not always correlate with in vivo data obtained in experimental models or during natural infections. Other host biological properties may intervene such as the body temperature, level of receptor expression, co-receptor, restriction factors, and genetic background. The spread of SARS-CoV-2 also depends on the extent and duration of viral shedding in the infected host as well as population density and behaviour (group living and grooming). Overall, current data indicate that the most at-risk interactions between humans and animals for COVID-19 infection are those involving certain mustelids (such as minks and ferrets), rodents (such as hamsters), lagomorphs (especially rabbits), and felines (including cats). Therefore, special attention should be paid to the risk of SARS-CoV-2 infection associated with pets.

scholarly journals Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2157
Author(s):  
Norbert Odolczyk ◽  
Ewa Marzec ◽  
Maria Winiewska-Szajewska ◽  
Jarosław Poznański ◽  
Piotr Zielenkiewicz
Keyword(s):  
Drug Development ◽  
Protein Interactions ◽  
Rna Virus ◽  
Antiviral Drug ◽  
Host Protein ◽  
Host Cells ◽  
Cell Surface Receptor ◽  
Short Peptides ◽  
Virus Protein ◽  
Positive Strand Rna

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein–protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development.

scholarly journals Therapeutic development by repurposing drugs targeting SARS-CoV-2 spike protein interactions by simulation studies

2021 ◽  
Author(s):  
Qazi Mohammad Sajid Jamal ◽  
Varish Ahmad ◽  
Ali H Alharbi ◽  
Mohammad Azam Ansari ◽  
Mohammad A Alzohairy ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Spike Protein ◽  
Simulation Studies ◽  
Therapeutic Development

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.

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