Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

/pdf/broad-host-range-of-sars-cov-2-predicted-by-comparative-and-2s68l6re29.pdf

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

/pdf/covid-19-associated-acute-kidney-injury-consensus-report-of-2bwe86imwi.pdf

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup.

The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

https://biorxiv.org/content/10.1101/2020.04.16.045302v1.full.pdf

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates.

Coronavirus disease (COVID-19) presents a broad spectrum of clinical manifestations ranging from an asymptomatic to a severe clinical course The host genetic background influence on the susceptibility and outcome of multiples infectious diseases has been previously reported Herein, we aimed to describe relevant identified genetic variants and those potentially related to the inter-individual variability of COVID-19 susceptibility and/or severity considering the physiopathological pathway of the disease The HLA-A*25:01, -B*15:27, -B*46:01, -C*01:02, and -C*07:29 alleles have been associated with COVID-19 susceptibility; while HLA-A*02:02, -B*15:03, and -C*12:03 have been identified as low-risk alleles Variants in cytokine genes such as IL1B, IL1R1, IL1RN, IL6, IL17A, FCGR2A, and TNF could be related to disease susceptibility and cytokine storm, and/or COVID-19 complications (eg, venous thrombosis) Several variants in ACE2 and TMPRSS2 affecting the expression of the receptors related to COVID-19 have been associated with the disease susceptibility and risk factors Finally, two GWAS have identified the loci 3p2131 (LZTFL1, SLC6A20, CCR9, FYCO1, CXCR6, and XCR1) and 9q342 (ABO) with COVID-19 severity Heterogeneous results in the association of genetic variants with COVID-19 susceptibility and severity were observed The mechanism of identified risk-genes and studies in different populations are still warranted

/pdf/genetics-insight-for-covid-19-susceptibility-and-severity-a-31rhnqt3xi.pdf

Genetics Insight for COVID-19 Susceptibility and Severity: A Review.

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.

The spread of the 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 via 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 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 the phylogeny 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 mutation accumulation. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to hACE2 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 human 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.

/pdf/interaction-of-the-spike-protein-rbd-from-sars-cov-2-with-2gdck3n0oy.pdf

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

The spread of the 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 via 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. We used homology-based protein-protein docking, binding energy estimation, and decomposition, aiming to predict both qualitative and quantitative aspects of the interaction. Using in silico structural modelling, we brought additional evidence that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than mutation accumulation. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to hACE2 and maintaining the stability of the interface. 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.

https://biorxiv.org/content/10.1101/2020.03.04.976027v1.full.pdf

In silico study of the spike protein from SARS-CoV-2 interaction with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

https://doi.org/10.1016/j.psj.2022.102253

Zied Bouslama

Papers

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.

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

In silico study of the spike protein from SARS-CoV-2 interaction with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

Phylogenetic and phylodynamic analyses of subtype-B metapneumovirus from chickens in Tunisia