Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.Objective: This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention

Complete genome sequence of Streptococcus pyogenes emm14 JS95, a necrotizing fasciitis strain isolated in Israel

10.1128/genomeA.00025-17Genome Announcements511e00025-1

Induction of endoplasmic reticulum stress and unfolded protein response constitutes a pathogenic strategy of group A streptococcus

10.3389/fcimb.2014.00105Frontiers in Cellular and Infection Microbiology4AUG10

An extracellular bacterial pathogen modulates host metabolism to regulate its own sensing and proliferation

10.1016/j.cell.2013.12.007Cell1561-297-108CELL

BA9 lineage of respiratory syncytial virus from across the globe and its evolutionary dynamics

<div><p>Respiratory syncytial virus (RSV) is an important pathogen of global significance. The BA9 is one of the most predominant lineages of the BA genotype of group B RSV that has acquired a 60bp duplication in its G protein gene. We describe the local and global evolutionary dynamics of the second hyper variable region in the C- terminal of the G protein gene of the BA9 lineage. A total of 418 sequences (including 31 study and 387 GenBank strains) from 29 different countries were used for phylogenetic analysis. This analysis showed that the study strains clustered with BA (BA9 and BA8) and SAB4 genotype of group B RSV. We performed time-scaled evolutionary clock analyses using Bayesian Markov chain Monte Carlo methods. We also carried out glycosylation, selection pressure, mutational, entropy and Network analyses of the BA9 lineage. The time to the most recent common ancestor (tMRCA) of the BA genotype and BA9 lineage were estimated to be the years 1995 (95% HPD; 1987–1997) and 2000 (95% HPD; 1998–2001), respectively. The nucleotide substitution rate of the BA genotype [(4.58×10⁻³ (95% HPD; 3.89–5.29×10⁻³) substitution/site/year] was slightly faster than the BA9 lineage [4.03×10⁻³ (95% HPD; 4.65–5.2492×10⁻³)]. The BA9 lineage was categorized into 3 sub lineages (I, II and III) based on the Bayesian and Network analyses. The local transmission pattern suggested that BA9 is the predominant lineage of BA viruses that has been circulating in India since 2002 though showing fluctuations in its effective population size. The BA9 lineage established its global distribution with report from 23 different countries over the past 16 years. The present study augments our understanding of RSV infection, its epidemiological dynamics warranting steps towards its overall global surveillance.</p></div

Amino acid mutations identified in positively selected sites of the BA9 lineage.

<p>Amino acid mutations identified in positively selected sites of the BA9 lineage.</p

Graphical representation of worldwide distribution of BA9 lineage of group B RSV; Color code bar in left side of the figure is used to represent the countries.

<p>The free available editable world map was downloaded from <a href="http://www.powerpointslides.net/fileadmin/user_upload/worldmap.ppt" target="_blank">http://www.powerpointslides.net</a> (<a href="http://www.powerpointslides.net/powerpointgraphics/powerpointmaps.html" target="_blank">http://www.powerpointslides.net/powerpointgraphics/powerpointmaps.html</a>). The map was created with PowerPoint and Adobe Photoshop.</p