scholarly journals Differential binding of SARS-CoV-2 Spike protein variants to its cognate receptor hACE2 using molecular modeling based binding analysis

2021 ◽  
Vol 17 (2) ◽  
pp. 337-347
Author(s):  
Anuja Krishnan ◽  
Keyword(s):  
Amino Acid ◽  
Hydrophobic Interactions ◽  
Viral Envelope ◽  
Angiotensin Converting Enzyme 2 ◽  
Phylogeny Analysis ◽  
Group A ◽  
Differential Binding ◽  
Group B ◽  
Novel Coronavirus ◽  
Protein Variants

The current emergence of novel coronavirus, SARS-CoV-2 and its ceaseless expansion worldwide has posed a global health emergency that has adversely affected the humans. With the entire world striving to understand the newly emerged virus, differences in morbidity and infection rate of SARS-CoV-2 have been observed across varied geographic areas, which have been ascribed to viral mutation and evolution over time. The homotrimeric Spike (S) glycoprotein on the viral envelope surface is responsible for binding, priming, and initiating infection in the host. Our phylogeny analysis of 1947 sequences of S proteins indicated there is a change in amino acid (aa) from aspartate (Group-A) to glycine (Group-B) at position 614, near the receptor- binding domain (RBD; aa positions 331-524). The two variants are reported to be in circulation, disproportionately across the world, with Group-A dominant in Asia and Group-B in North America. The trimeric, monomeric, and RBD of S protein of both the variant groups (A & B) were modeled using the Swiss-Model server and were docked with the human receptor angiotensin-converting enzyme 2 (hACE2) employing the PatchDock server and visualized in PyMol. Group-A S protein’s RBD bound imperceptibly to the two binding clefts of the hACE2 protein, on the other hand, Group-B S protein’s RBD perfectly interacted inside the binding clefts of hACE2, with higher number of hydrogen and hydrophobic interactions. This implies that the S protein’s amino acid at position 614 near the core RBD influences its interaction with the cognate hACE2 receptor, which may induce its infectivity that should be explored further with molecular and biochemical studies.

scholarly journals Differential binding of SARS-CoV-2 Spike protein variants to its cognate receptor hACE2 using molecular modeling based binding analysising molecular modeling based binding analysis

2021 ◽  
Vol 17 (2) ◽  
pp. 337-347
Author(s):  
Anuja Krishnan ◽  
Keyword(s):  
Amino Acid ◽  
Molecular Modeling ◽  
Hydrophobic Interactions ◽  
Viral Envelope ◽  
Angiotensin Converting Enzyme 2 ◽  
Phylogeny Analysis ◽  
Group A ◽  
Group B ◽  
Novel Coronavirus ◽  
Protein Variants

The current emergence of novel coronavirus, SARS-CoV-2 and its ceaseless expansion worldwide has posed a global health emergency that has adversely affected the humans. With the entire world striving to understand the newly emerged virus, differences in morbidity and infection rate of SARS-CoV-2 have been observed across varied geographic areas, which have been ascribed to viral mutation and evolution over time. The homotrimeric Spike (S) glycoprotein on the viral envelope surface is responsible for binding, priming, and initiating infection in the host. Our phylogeny analysis of 1947 sequences of S proteins indicated there is a change in amino acid (aa) from aspartate (Group-A) to glycine (Group-B) at position 614, near the receptor- binding domain (RBD; aa positions 331-524). The two variants are reported to be in circulation, disproportionately across the world, with Group-A dominant in Asia and Group-B in North America. The trimeric, monomeric, and RBD of S protein of both the variant groups (A & B) were modeled using the Swiss-Model server and were docked with the human receptor angiotensin-converting enzyme 2 (hACE2) employing the PatchDock server and visualized in PyMol. Group-A S protein’s RBD bound imperceptibly to the two binding clefts of the hACE2 protein, on the other hand, Group-B S protein’s RBD perfectly interacted inside the binding clefts of hACE2, with higher number of hydrogen and hydrophobic interactions. This implies that the S protein’s amino acid at position 614 near the core RBD influences its interaction with the cognate hACE2 receptor, which may induce its infectivity that should be explored further with molecular and biochemical studies.

scholarly journals Genetic Variation and Evolution of the 2019 Novel Coronavirus

2021 ◽  
pp. 1-13
Author(s):  
Salvatore Dimonte ◽  
Muhammed Babakir-Mina ◽  
Taib Hama-Soor ◽  
Salar Ali
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Rapid Evolution ◽  
Single Amino Acid ◽  
Angiotensin Converting Enzyme 2 ◽  
New Type ◽  
Amino Acid Mutations ◽  
Host Infection ◽  
Human Coronaviruses ◽  
Novel Coronavirus

<b><i>Introduction:</i></b> SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. <b><i>Methods:</i></b> This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. <b><i>Results:</i></b> The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. <b><i>Discussion/Conclusion:</i></b> Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

scholarly journals Amino acid infusion in oligohydromnios and increase in AFI and impact on perinatal outcome

2019 ◽  
Vol 8 (2) ◽  
pp. 617
Author(s):  
Isha Sunil ◽  
Chejerla Sunitha ◽  
Harkirat Kaur
Keyword(s):  
Amino Acid ◽  
Perinatal Outcome ◽  
Perinatal Outcomes ◽  
Apgar Scores ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Vaginal Deliveries ◽  
Group A ◽  
One Year ◽  
Group B

Background: Decreased amniotic fluid is related to adverse maternal and perinatal outcomes. The purpose of this study was to evaluate the role of amino acid infusion in patients of oligohydromnios and compare the perinatal outcome in the two groups.Methods: This study was conducted in the Department of Obstetrics and Gynaecology, ASCOMS Hospital, Jammu for a period of one year from October 2017 to September 2018. A total of 50 women with AFI <8 cm were enrolled in the study . They were divided into two groups of 25 each. Group A were given amino acid infusion and Group B were not given any intervention. These were compared for increase in AFI and perinatal outcome.Results: In the present study, the gain in AFI in Group A was 2.32 ± 0.67 and in group B was 1.32 ± 1.03 which was statistically significant. The perinatal outcome was better Group A compared to Group B with decreased incidence of meconium stained liquor, low birth weight, low APGAR scores and NICU admissions and increase in vaginal deliveries as compared to caesarean sections.Conclusions: The present study suggests that parentral transfusion of amino acid in cases of oligohydromnios significantly increases the AFI of the patient and decreases the incidence of caesarean sections, meconium stained liquor, low APGAR scores and NICU admissions.

scholarly journals Is Novel Coronavirus Novel: Covid-19, A Pandemic or An Endemic?

2020 ◽  
Author(s):  
Sangam Banerjee
Keyword(s):  
Disease Progression ◽  
Herd Immunity ◽  
Threshold Value ◽  
Acquired Immunity ◽  
Test Results ◽  
Serological Survey ◽  
Previous Infection ◽  
Group A ◽  
Group B ◽  
Novel Coronavirus

We have analysed the death and recovery rate of Covid-19 disease progression. From the analysis, we have argued that the pandemic is over in certain countries (labelled as group-A) and for other countries (labelled as group-B) the disease appears to remain as endemic. Taking into account the serological survey (sero-survey) test results obtained by certain groups and comparing it with herd immunity threshold value one can infer that the low number of infection for group-B is either due to acquired immunity by some previous infection by other coronavirus or due to innate immunity towards this infection. This effect is stronger for group-B to slow the progress of the disease to such an extent resulting in flattening of the disease progression curve compared to group-A.

scholarly journals Purification, properties and partial amino acid sequence of the blood-group-A-gene-associated α-3-N-acetylgalactosaminyltransferase from human gut mucosal tissue

1990 ◽  
Vol 271 (1) ◽  
pp. 93-98 ◽  
Author(s):  
N Navaratnam ◽  
J B C Findlay ◽  
J N Keen ◽  
W M Watkins
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Blood Group ◽  
Specific Activity ◽  
Mucosal Tissue ◽  
Human Gut ◽  
Partial Amino Acid Sequence ◽  
Blood Group A ◽  
Group A ◽  
Group B

An alpha-3-N-acetylgalactosaminyltransferase that transfers N-acetylgalactosamine from UDP-N-acetylgalactosamine to H-active structures to form A determinants was purified to homogeneity from human gut mucosal tissue of blood-group-A subjects. The mucosa was homogenized, then treated with Triton X-100, and the solubilized enzyme was purified by affinity chromatography on UDP-hexanolamine-agarose and octyl-Sepharose CL-4B. Enzyme activity was recovered in 44% yield with a specific activity of approx. 7 mumol/min per mg. The only effective acceptor substrates for the transferase were those containing a subterminal β-galactosyl residue substituted at the O-2 position with L-fucose. The purified enzyme had a weak capacity to transfer D-galactose from UDP-D-galactose to similar acceptors to make blood-group-B determinants. H.p.l.c. and SDS/PAGE analysis indicated an Mr of 40,000 for the purified enzyme. For the first time a partial amino acid sequence Xaa-Ser-Leu-Pro-Arg-Met-Val-Tyr-Pro-Gln-Ile-Ser?-Val-Leu was obtained for the N-terminal region of the soluble alpha-3-N-acetylgalactosaminyltransferase.

scholarly journals A Single Amino Acid Change within Antigenic Domain II of the Spike Protein of Bovine Coronavirus Confers Resistance to Virus Neutralization

2001 ◽  
Vol 8 (2) ◽  
pp. 297-302 ◽  
Author(s):  
Dongwan Yoo ◽  
Dirk Deregt
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Single Point Mutation ◽  
Bovine Coronavirus ◽  
Single Amino Acid Change ◽  
Group A ◽  
Escape Mutants ◽  
Group B

ABSTRACT The spike glycoprotein is a major neutralizing antigen of bovine coronavirus (BCV). Conformational neutralizing epitopes of group A and group B monoclonal antibodies (MAbs) have previously been mapped to two domains at amino acids 351 to 403 (domain I) and amino acids 517 to 621 (domain II). To further map antigenic sites, neutralization escape mutants of BCV were selected with a group A MAb which has both in vitro and in vivo virus-neutralizing ability. The escape mutants were demonstrated to be neutralization resistant to the selecting group A MAb and remained sensitive to neutralization by a group B MAb. In radioimmunoprecipitation assays, the spike proteins of neutralization escape mutants were shown to have lost their reactivities with the selecting group A MAb. Sequence analysis of the spike protein genes of the escape mutants identified a single nucleotide substitution of C to T at position 1583, resulting in the change of alanine to valine at amino acid position 528 (A528V). The mutation occurs in domain II and in a location which corresponds to the hypervariable region of the spike protein of the coronavirus mouse hepatitis virus. Experimental introduction of the A528V mutation into the wild-type spike protein resulted in the loss of MAb binding of the mutant protein, confirming that the single point mutation was responsible for the escape of BCV from immunological selective pressure.

scholarly journals Innovation of Audio-Visual Triage system in Combating the Spread of COVID-19 Infection and its efficacy: A Novel Strategy

2020 ◽  
Author(s):  
Muhammad Mansoor Hafeez ◽  
Mohammad Azhar ◽  
Hafiz Rizwan Zafar Chudhary ◽  
Muhammad Asim Rana ◽  
Arif Malik
Keyword(s):  
Healthcare Professionals ◽  
The Novel ◽  
Current Analysis ◽  
Triage System ◽  
Group A ◽  
Anxiety Levels ◽  
Novel Strategy ◽  
Group B ◽  
Novel Coronavirus ◽  
Almost All

ABSTRACTDuring the novel coronavirus pandemic, also known as SARS-CoV-2 or COVID-19 pandemic, frontline healthcare professionals suffered psychological as well as pathological trauma due to the lack of preparation to cope with this unforeseen situation. The protocols to prevent the spread of this disease proved to be less effective than anticipated. In these circumstances, improvement of the existing triage system was felt and an AUDIO-VISUAL TRIAGE (AVT) system was introduced to enhance confidence as well as increase the safety of frontline healthcare professionals. The current analysis was performed from March 21, 2020, to April 28, 2020, until the completion of sixty response forms, at Bahria Town International Hospital, Lahore. Thirty participants (Group A) deployed on visual triage and other thirty (Group B) on AVT for screening suspected cases of COVID-19 infection. Anxiety levels were measured by using the GAD-7 scoring system and the participants of both groups were periodically tested for COVID-19 infection by PCR. Independent t-test was used to evaluate the significance of different variables at a confidence level of 95%. The result of the current study revealed the effectiveness of AVT for the screening of COVID-19 patients. There was a statistically significant increase in anxiety levels and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rate in group A as compared to group B. Almost all participants in group A wanted to shift their place of work or ready to quit the job if they were forced to perform their duties at the same visual triage. AVT system for COVID-19 screening found to be more safe and less stressful than visual triage. It is not only a simple and effective way to prevent the spread of diseases but also boosted the confidence of frontline healthcare professionals to fight against coronavirus spread.

scholarly journals The COVID-19 pandemic: a global health crisis

2020 ◽  
Vol 52 (11) ◽  
pp. 549-557
Author(s):  
Casey A. Pollard ◽  
Michael P. Morran ◽  
Andrea L. Nestor-Kalinoski
Keyword(s):  
Pulmonary Fibrosis ◽  
Geographic Location ◽  
The United States ◽  
Viral Envelope ◽  
Lung Epithelial Cells ◽  
World Health ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Health Organization

The novel coronavirus SARS-CoV-2 was identified as the causative agent for a series of atypical respiratory diseases in the Hubei Province of Wuhan, China in December of 2019. The disease SARS-CoV-2, termed COVID-19, was officially declared a pandemic by the World Health Organization on March 11, 2020. SARS-CoV-2 contains a single-stranded, positive-sense RNA genome surrounded by an extracellular membrane containing a series of spike glycoproteins resembling a crown. COVID-19 infection results in diverse symptoms and morbidity depending on individual genetics, ethnicity, age, and geographic location. In severe cases, COVID-19 pathophysiology includes destruction of lung epithelial cells, thrombosis, hypercoagulation, and vascular leak leading to sepsis. These events lead to acute respiratory distress syndrome (ARDS) and subsequent pulmonary fibrosis in patients. COVID-19 risk factors include cardiovascular disease, hypertension, and diabetes, which are highly prevalent in the United States. This population has upregulation of the angiotensin converting enzyme-2 (ACE2) receptor, which is exploited by COVID-19 as the route of entry and infection. Viral envelope proteins bind to and degrade ACE2 receptors, thus preventing normal ACE2 function. COVID-19 infection causes imbalances in ACE2 and induces an inflammatory immune response, known as a cytokine storm, both of which amplify comorbidities within the host. Herein, we discuss the genetics, pathogenesis, and possible therapeutics of COVID-19 infection along with secondary complications associated with disease progression, including ARDS and pulmonary fibrosis. Understanding the mechanisms of COVID-19 infection will allow the development of vaccines or other novel therapeutic approaches to prevent transmission or reduce the severity of infection.

scholarly journals The clinical characteristics of hip fracture: during the novel coronavirus disease (COVID-19) epidemic

2020 ◽  
Author(s):  
Hongjie Zhang ◽  
Zengping Lin ◽  
Jiping Zhong ◽  
Darong Nie ◽  
Hongmei Song ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Medical Treatment ◽  
Exposure Time ◽  
Light Exposure ◽  
The Novel ◽  
Hospitalization Cost ◽  
Epidemic Period ◽  
Group A ◽  
Group B ◽  
Novel Coronavirus

Abstract Background The aim of this study was to assess the characteristics of hip fracture during the novel coronavirus (COVID-19) epidemic.Method Hip-facture patients undergoing surgery from January 26 to March 31, 2020 (group A) and from January 26 to March 31, 2019 (group B) were retrospectively included. The durations from injury onset to hospital discharge, hospitalization cost, comorbidity, and complications of patients in the two groups were collected. The daily activity and light exposure time, and medical treatment interruption of patients in group A before and during their self-quarantine were also collected. In addition, the reasons for those with hospital admission delay were inquired.Results During the COVID-19 epidemic, patients with hip fracture was increased by 9 cases (69.23%). Patients in group A underwent an over 20-hour longer duration from the injury onset to hospital, an over 3-day longer hospitalization stay, and more hospitalization cost of over 4-thousand yuan compared with those for patients in group B (P < 0.05). The self-quarantine led to reduced daily activities (P <0.001), reduced light exposure time (P <0.001) and more medical interruption for hip-fracture patients. There were also slight more comorbidity number and perioperative complications for patients in group A compared with patients in group B. For those with a pre-hospital time more than 24 h, 58.33% feared go out for medical treatment because of the COVID-19 epidemic.Conclusion During the COVID-19 epidemic period, the prevention and management of hip-fracture for the elderly require more attention for the public and medical care personnel.

Effects of early amino acid administration during total parenteral nutrition on protein metabolism in pre-term infants

1992 ◽  
Vol 82 (2) ◽  
pp. 199-203 ◽  
Author(s):  
R. A. van Lingen ◽  
J. B. van Goudoever ◽  
I. H. T. Luijendijk ◽  
J. L. D. Wattimena ◽  
P. J. J. Sauer
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Birth Weight ◽  
Amino Acid ◽  
Protein Breakdown ◽  
Protein Balance ◽  
15N Enrichment ◽  
Group A ◽  
Group B ◽  
Acid Administration

1. We investigated the effects of starting amino acid administration on post-natal day 2 on protein turnover and nitrogen balance in appropriate-for-gestational-age, very-low-birth-weight infants. Eighteen infants were divided into two groups. Group A received from day 2 onwards an amino acid solution, whereas group B started on this solution after day 4. Both groups were exclusively parenterally fed, 200 kJ day−1 kg−1 on post-natal days 3 and 4. Group A (birth weight 1.5 ± 0.3 kg) received 4.6 g of glucose, 1.9 g of fat and 2.3 g of amino acids day−1 kg−1 body weight. Group B (birth weight 1.4 ± 0.2 kg) received 7.0 g of glucose and 1.9 g of fat day−1 kg−1 body weight. 2. At post-natal day 3, a primed constant infusion of 3 mg of [15N]glycine day−1 kg−1 was given. Protein flux, protein synthesis and protein breakdown were calculated from the 15N enrichment in urinary ammonia. In five out of nine infants in group B no plateau of 15N enrichment in urinary urea could be detected, whereas in group A two out of nine infants did not reach a plateau. For this reason we did not use the end product urea for our calculations. 3. The administration of the amino acids resulted in a higher protein flux (6.9 ± 1.5 g day−1 kg−1 versus 5.2 ± 0.9 g day−1 kg−1) and a higher protein synthesis rate (6.0 ± 1.4 g day−1 kg−1 versus 4.6 ± 0.8 g day−1 kg−1) in group A. There was no statistically significant difference in protein breakdown. The administration of amino acids reversed a negative protein balance (−0.6 ± 0.2 g day−1 kg−1) into a positive one (1.4 ± 0.2 g day−1 kg−1. No adverse effects of the amino acid infusion were seen. 4. We conclude that the early introduction of amino acids has, even at this relatively low energy intake of 200 kJ day−1 kg−1, a positive effect on protein balance by increasing protein synthesis.

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