Sequence difference of angiotensin-converting enzyme 2 between nonhuman primates affects its binding-affinity with SARS-CoV-2 S receptor binding domain

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused many deaths and contributed to a tremendous public health concern worldwide since 2020.Angiotensin-converting enzyme 2(ACE2)binds to the SARS-CoV-2 virus as a receptor.The challenge of different nonhuman primate(NHP)species by SARSCoV-2 virus demonstrated different effects on virus replication and disease pathology.This study characterizes differences between host ACE2 sequences of three NHP species:Macaca mulatta,Macaca fascicularis,and Chlorocebus sabaeus.In addition,the binding affinity between the ACE2 ectodomain and the SARS-CoV-2 S receptor-binding domain(RBD)was analyzed.Variation of ACE2 sequence among NHP species and the binding affinity may account for different susceptibility and responses to SARS-CoV-2 infection.

Clinical and genetic characteristics of a child with Sotos syndrome and attention-deficit/hyperactivity disorder:A case report

BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty.CASE SUMMARY The patient presented with accelerated growth and advanced skeletal maturation;however,she lacked any distinct facial characteristics related to specific genetic disorders.Genetic analyses revealed a paternally inherited heterozygous synonymous mutation[c.4605C>T(p.Arg1535Arg)].Functional analyses suggested that this mutation may disrupt splicing,and bioinformatics analyses predicted that this mutation was likely pathogenic.After an initial diagnosis of Sotos syndrome,the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months.CONCLUSION The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.

Molecular dynamics-driven exploration of peptides targeting SARS-CoV-2,with special attention on ACE2,S protein,M^(pro),and PL^(pro):A review

Molecular dynamics(MD)simulation is a computational technique that analyzes the movement of a system of particles over a given period.MD can provide detailed information about the fluctuations and conformational changes of biomolecules at the atomic level over time.In recent years,MD has been widely applied to the discovery of peptides and peptide-like molecules that may serve as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inhibitors.This review summarizes recent advances in such explorations,focusing on four protein targets:angiotensin-converting enzyme 2(ACE2),spike protein(S protein),main protease(M^(pro)),and papain-like protease(PL^(pro)).These four proteins are important druggable targets of SARS-CoV-2 because of their roles in viral entry,maturation,and infectivity of the virus.A review of the literature revealed that ACE2,S protein,and M^(pro) have received more attention in MD research than PL^(pro).Inhibitors of the four targets identified by MD simulations included peptides derived from food and other bioresources,peptides designed using the targets as templates,and peptide-like molecules retrieved from databases.Many of the inhibitors have yet to be validated in experimental assays for potency.Nevertheless,the role of MD simulation as an efficient tool in the early stages of anti-SARS-CoV-2 drug discovery agents has been demonstrated.

Prediction of Proteins Associated with COVID-19 Based Ligand Designing and Molecular Modeling

Current understanding about how the virus that causes COVID-19 spreads is largely based on what is known about similar coronaviruses.Some of the Natural products are suitable drugs against SARS-CoV-2 main protease.For recognizing a strong inhibitor,we have accomplished dock-ing studies on the major virus protease with 4 natural product species as anti COVID-19(SARS-CoV-2),namely“Vidarabine”,“Cytarabine”,“Gem-citabine”and“Matrine”which have been extracted fromGillan’s leaves plants.These are known as Chuchaq,Trshvash,Cote-Couto and Khlvash in Iran.Among these four studied compounds,Cytarabine appears as a suitable com-pound with high effectiveness inhibitors to this protease.Finally by this work we present a method on the Computational Prediction of Protein Structure Associated with COVID-19 Based Ligand Design and Molecular Modeling.By this investigation,auto dock software(iGEM-DOCK)has been used and via this tool,the suitable receptors can be distinguished in whole COVID-19 component structures for forming a complex.“iGEMDOCK”is suitable to define the binding site quickly.With docking simulation and NMR inves-tigation,we have demonstrated these compounds exhibit a suitable binding energy around 9 Kcal/mol with various ligand proteins modes in the bind-ing to COVID-19 viruses.However,these data need further evaluation for repurposing these drugs against COVID-19 viruses,in both vivo&vitro.

The S190R mutation in the hemagglutinin protein of pandemic H1N1 2009 influenza virus increased its pathogenicity in mice

Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients’ respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus.

Inactivating SARS-CoV-2 by electrochemical oxidation

Fully inactivating SARS-Co V-2, the virus causing coronavirus disease 2019, is of key importance for interrupting virus transmission but is currently performed by using biologically or environmentally hazardous disinfectants. Herein, we report an eco-friendly and efficient electrochemical strategy for inactivating the SARS-Co V-2 using in-situ formed nickel oxide hydroxide as anode catalyst and sodium carbonate as electrolyte. At a voltage of 5 V, the SARS-Co V-2 viruses can be rapidly inactivated with disinfection efficiency reaching 95% in only 30 s and 99.99% in 5 min. Mass spectrometry analysis and theoretical calculations indicate that the reactive oxygen species generated on the anode can oxidize the peptide chains and induce cleavage of the peptide backbone of the receptor binding domain of the SARS-Co V-2 spike glycoprotein, and thereby disables the virus. This strategy provides a sustainable and highly efficient approach for the disinfection of the SARS-CoV-2 viruliferous aerosols and wastewater.