Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein.

The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild-type molecule. Most ACE2 variants showed a similar binding affinity for SARS-CoV-2 spike protein as observed in the complex structure of wild-type ACE2 and SARS-CoV-2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS-CoV-2 infection driven by ACE2 allelic variants.

Molecular docking between human TMPRSS2 and SARS-CoV-2 spike protein: conformation and intermolecular interactions.

Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. The present study aims to investigate the conformational attributes of the molecular complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike protein. Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. In summary, the present study provides structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.

Dataset for homologous proteins in Drosophila melanogaster for SARS-CoV-2/human interactome.

Animal modelling for infectious diseases is critical to understand the biology of the pathogens including viruses and to develop therapeutic strategies against it. Herein, we present the sequence homology and expression data analysis of proteins found in Drosophila melanogaster that are orthologous to human proteins, reported as components of SARS-CoV-2/Human interactome. The dataset enlists sequence homology, query coverage, domain conservation, OrthoMCL and Ensembl Genome Browser support of 326 proteins in D.melanogaster that are potentially orthologous to 417 human proteins reported for their direct physical interactions with 28 proteins encoded by SARS-CoV-2 genome. Expression of these D.melanogaster orthologous genes in 26 anatomical positions are also plotted as heat maps in 27 sets, corresponding to the potential protein interactors for each viral protein. The data could be used to direct experiments and potentially predict their phenotypic and molecular outcome in order to dissect the biological roles and molecular functionality of SARS-CoV-2 proteins in a convenient animal model system like D.melanogaster.

Torture in Egypt.

This article is concerned with the increasing prevalence of torture in Egypt. Torture is a widespread problem in Egypt, being practiced in the majority of police stations and state security places. It has become a routine practice and is seen daily on a systematic basis. The number of people who are subjected every month to torture is unimaginable. In addition, there are deaths that occur as a result of the torture. However, the Egyptian government does not give clear answers about the issue. Everyone could be exposed to torture, and for different, illogical reasons. The case of Bany Mazar is a horribly clarifying one. The unclear political situation and the absence of democracy play the main role in the highly increasing rate of torture in Egypt.