scholarly journals COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

2020 ◽  
Author(s):  
liu wenzhong ◽  
Li hualan
Keyword(s):  
Molecular Docking ◽  
Cytochrome C ◽  
Viral Proteins ◽  
Domain Analysis ◽  
Heme Iron ◽  
The Novel ◽  
Beta Chain ◽  
Conserved Domain ◽  
Novel Coronavirus

<p>The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory caused by the novel coronavirus. The virus is the positive-strand RNA one with high homology to bat coronavirus. The pathogenic mechanism of the new coronavirus is still unclear, which is a significant obstacle to the development of drugs and patients' rescue. In this study, conserved domain analysis, homology modeling, and molecular docking were made to compare the biological roles of specific proteins belonging to the novel coronavirus. The conserved domain analysis showed envelope protein (E), nucleocapsid phosphoprotein (N) and ORF3a had heme linked sites, which Arg134 of ORF3a, Cys44 of E, Ile304 of N were the heme-iron linked site, respectively. ORF3a also possessed the conserved domains of human cytochrome C reductases and bacterial EFeB protein. These three domains were highly overlapping so that ORF3a could dissociate the iron of heme to form porphyrin. Heme linked sites of E protein may be relevant to the high infectivity, and the role of heme linked sites of N protein may be related to the virus replication. The docking results showed that orf1ab, ORF10, and ORF3a proteins coordinated to attack the 1-beta chain of hemoglobin, and some structural and non-structural viral proteins could bind porphyrin. Deoxyhemoglobin was more vulnerable to virus attacks than oxidized hemoglobin. But ORF3a was specific and would not attack blue blood protein, normal cytochrome C, and peroxidase. As for the attack, it would cause increasingly less hemoglobin that could carry oxygen and carbon dioxide, thus producing symptoms of respiratory distress and coagulation reaction, damaging many organs and tissues. The mechanism also interfered with the normal heme anabolic pathway of the human body, expecting to cause human diseases. Based on the small molecule drug library, drugbank, we searched for drugs bound to viral proteins by molecular docking. The results showed that some anticancer drugs could attach to the heme-iron linked site of ORF3a and N. Remdesivir was relatively more obvious than Hydroxychloroquine and Chloroquine in terms of the binding capacity of ORF3a, but the combined role of three drugs to ORF3a was lower. Unfortunately, no drug could bind to the heme-iron linked site of E. Besides, these higher binding energies may prevent all screened drugs from binding firmly to viral proteins. Since there were no clinical data, so inhibitory effects on ORF3a and N were still unclear. This theory is only for academic discussion and needed to be verified by other experiments. Please consult a qualified doctor for treatment details. Due to the toxicity and side effects of drugs, do not use medicines yourself. We expect these discoveries to bring more ideas to people to relieve patients' symptoms and save more lives.<br></p>

scholarly journals COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

2020 ◽  
Author(s):  
liu wenzhong ◽  
Li hualan
Keyword(s):  
Molecular Docking ◽  
Cytochrome C ◽  
Viral Proteins ◽  
Domain Analysis ◽  
Heme Iron ◽  
The Novel ◽  
Beta Chain ◽  
Conserved Domain ◽  
Novel Coronavirus

<p>The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory caused by the novel coronavirus. The virus is the positive-strand RNA one with high homology to bat coronavirus. The pathogenic mechanism of the new coronavirus is still unclear, which is a significant obstacle to the development of drugs and patients' rescue. In this study, conserved domain analysis, homology modeling, and molecular docking were made to compare the biological roles of specific proteins belonging to the novel coronavirus. The conserved domain analysis showed envelope protein (E), nucleocapsid phosphoprotein (N) and ORF3a had heme linked sites, which Arg134 of ORF3a, Cys44 of E, Ile304 of N were the heme-iron linked site, respectively. ORF3a also possessed the conserved domains of human cytochrome C reductases and bacterial EFeB protein. These three domains were highly overlapping so that ORF3a could dissociate the iron of heme to form porphyrin. Heme linked sites of E protein may be relevant to the high infectivity, and the role of heme linked sites of N protein may be related to the virus replication. The docking results showed that orf1ab, ORF10, and ORF3a proteins coordinated to attack the 1-beta chain of hemoglobin, and some structural and non-structural viral proteins could bind porphyrin. Deoxyhemoglobin was more vulnerable to virus attacks than oxidized hemoglobin. But ORF3a was specific and would not attack blue blood protein, normal cytochrome C, and peroxidase. As for the attack, it would cause increasingly less hemoglobin that could carry oxygen and carbon dioxide, thus producing symptoms of respiratory distress and coagulation reaction, damaging many organs and tissues. The mechanism also interfered with the normal heme anabolic pathway of the human body, expecting to cause human diseases. Based on the small molecule drug library, drugbank, we searched for drugs bound to viral proteins by molecular docking. The results showed that some anticancer drugs could attach to the heme-iron linked site of ORF3a and N. Remdesivir was relatively more obvious than Hydroxychloroquine and Chloroquine in terms of the binding capacity of ORF3a, but the combined role of three drugs to ORF3a was lower. Unfortunately, no drug could bind to the heme-iron linked site of E. Besides, these higher binding energies may prevent all screened drugs from binding firmly to viral proteins. Since there were no clinical data, so inhibitory effects on ORF3a and N were still unclear. This theory is only for academic discussion and needed to be verified by other experiments. Please consult a qualified doctor for treatment details. Due to the toxicity and side effects of drugs, do not use medicines yourself. We expect these discoveries to bring more ideas to people to relieve patients' symptoms and save more lives.<br></p>

scholarly journals COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

2021 ◽  
Author(s):  
liu wenzhong ◽  
li hualan
Keyword(s):  
Binding Sites ◽  
Cell Function ◽  
Viral Infections ◽  
Immune Cell ◽  
Viral Proteins ◽  
Heme Iron ◽  
The Novel ◽  
Beta Chain ◽  
Heme Metabolism ◽  
Novel Coronavirus

The novel coronavirus pneumonia is a contagious acute respiratory disease caused by the SARS-COV-2 coronavirus. The pathogenic mechanism of the novel coronavirus is unknown, which presents a significant impediment to the patient rescue. A conserved domain search strategy was utilized in this work to determine that a large number of viral proteins could bind to hemoglobin. S could bind to extracellular hemoglobin. SARS-COV-2 virus proteins interacted with porphyrins. SARS-COV-2 viruses could synthesize heme from porphobilinogen and encode all the similar enzymes required for the process. Both E and ORF3a contained heme-binding sites. ORF3a's Arg134 and E's Cys44 were the heme-iron binding sites, respectively. ORF3a also contained homologous domains to human cytochrome C reductase and bacterial EFeB protein. The molecular docking analysis revealed that ORF3a and ORF8 proteins were shown to be capable of attacking hemoglobin's 1-beta chain, whereas ORF3a was found to be effective in capturing heme for dissociation to iron and porphyrin. Deoxyhemoglobin was more susceptible to viral attack than oxidized hemoglobin. In summary, the combination of viral proteins to porphyrins and their metal compounds would improve the ability to permeate cell membranes and generate oxygen free radicals (ROS). It may be associated with viral infections and epidemic transmission. Viral proteins regulated the production and function of NO, CO and CO2 by inhibiting the activity of hemoglobin, thereby affecting immune cell function. Viral proteins' attack on hemoglobin could result in symptoms such as respiratory distress and blood clotting, damage to numerous organs and tissues, and disruption of normal human heme metabolism.

scholarly journals Molecular Docking Studies of some Antiviral and Antimalarial Drugs Via Bindings to 3CL-Protease and Polymerase Enzymes of the Novel Coronavirus (SARS-CoV-2)

2020 ◽  
Vol 10 (5) ◽  
pp. 6444-6459 ◽  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Antimalarial Drugs ◽  
The Novel ◽  
Rapid Spread ◽  
Novel Virus ◽  
Novel Coronavirus ◽  
3Cl Protease ◽  
Insight Into

The rapid spread of the novel coronavirus (SARS-CoV-2) as a serious threat to the world public health is in dire need of finding potential therapeutic agents. Chinese have tested several antiviral and antimalarial drugs as potent inhibitors for the novel virus, such as remdesivir, chloroquine, hydroxychloroquine, umifenovir and favipiravir. In this study, we used the molecular docking models to study the binding interactions between these pharmaceuticals, as well as our proposed remdesivir analogue (AZCV-20) with the 3CLpro and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2, using MEO and Autodock4 methods. Our study provides insight into the possible role of structural flexibility and efficacy during interactions between 3CLpro, RdRp and the drugs.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

The role and relationship of mindreading and social attunement in HRI – position statements of interdisciplinary researchers. Workshop HRI'20

2020 ◽  
Author(s):  
Agnieszka Wykowska ◽  
Jairo Pérez-Osorio ◽  
Stefan Kopp
Keyword(s):  
Mental States ◽  
Human Robot Interaction ◽  
Human Interaction ◽  
Artificial Agents ◽  
The Novel ◽  
Robot Interaction ◽  
Novel Coronavirus ◽  
Relationship Of ◽  
The Relationship

This booklet is a collection of the position statements accepted for the HRI’20 conference workshop “Social Cognition for HRI: Exploring the relationship between mindreading and social attunement in human-robot interaction” (Wykowska, Perez-Osorio &amp; Kopp, 2020). Unfortunately, due to the rapid unfolding of the novel coronavirus at the beginning of the present year, the conference and consequently our workshop, were canceled. On the light of these events, we decided to put together the positions statements accepted for the workshop. The contributions collected in these pages highlight the role of attribution of mental states to artificial agents in human-robot interaction, and precisely the quality and presence of social attunement mechanisms that are known to make human interaction smooth, efficient, and robust. These papers also accentuate the importance of the multidisciplinary approach to advance the understanding of the factors and the consequences of social interactions with artificial agents.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

scholarly journals Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li
Keyword(s):  
Genetic Variation ◽  
The Novel ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Missense Variants ◽  
Catalytic Metal ◽  
Using Data ◽  
Novel Coronavirus ◽  
Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

scholarly journals Discovery of alliin as a putative inhibitor of the main protease of SARS-CoV-2 by molecular docking

BioTechniques ◽  
2020 ◽  
Vol 69 (2) ◽  
pp. 108-112 ◽  
Author(s):  
Bijun Cheng ◽  
Tianjiao Li
Keyword(s):  
Molecular Docking ◽  
Pharmaceutical Compounds ◽  
The Novel ◽  
Important Target ◽  
Main Protease ◽  
Docking Method ◽  
Life Threatening ◽  
Novel Coronavirus ◽  
Better Than ◽  
Molecular Docking Method

The outbreak of viral pneumonia caused by the novel coronavirus SARS-CoV-2 that began in December 2019 caused high mortality. It has been suggested that the main protease (Mpro) of SARS-CoV-2 may be an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. Remdesivir, ritonavir and chloroquine have all been reported to play a role in suppressing SARS-CoV-2. Here, we applied a molecular docking method to study the binding stability of these drugs with SARS-CoV-2 Mpro. It appeared that the ligand–protein binding stability of the alliin and SARS-CoV-2 Mpro complex was better than others. The results suggested that alliin may serve as a good candidate as an inhibitor of SARS-CoV-2 Mpro. Therefore, the present research may provide some meaningful guidance for the prevention and treatment of SARS-CoV-2.

scholarly journals Arterial Hypertension as a Risk Comorbidity Associated with COVID-19 Pathology

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Alexander Kamyshnyi ◽  
Inna Krynytska ◽  
Victoriya Matskevych ◽  
Mariya Marushchak ◽  
Oleh Lushchak
Keyword(s):  
Arterial Hypertension ◽  
Pressure Control ◽  
The Novel ◽  
Global Public Health ◽  
Angiotensin Converting Enzyme 2 ◽  
Cardiovascular Comorbidities ◽  
Public Health Challenge ◽  
Novel Coronavirus ◽  
Ace2 Gene

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is an ongoing global public health challenge. Current clinical data suggest that, in COVID-19 patients, arterial hypertension (AH) is one of the most common cardiovascular comorbidities; it can worsen outcomes and increase the risk of admission to intensive care unit (ICU). The exact mechanisms through which AH contributes to the poor prognosis in COVID-19 are not yet clear. The putative relationship between AH and COVID-19 may be linked to the role of angiotensin-converting enzyme 2 (ACE2), a key element of the AH pathophysiology. Another mechanism connecting AH and COVID-19 is the dysregulation of the immune system resulting in a cytokine storm, mediated by an imbalanced response of T helper cells subtypes. Therefore, it is essential to optimize blood pressure control in hypertensive patients and monitor them carefully for cardiovascular and other complications for the duration of COVID-19 infection. The question whether AH-linked ACE2 gene polymorphisms increase the risk and/or worsen the course of SARS-CoV-2 infection should also receive further consideration.

scholarly journals The Role of Dental Professionals in Pandemic Events and Disaster Responses

2020 ◽  
pp. 1-5 ◽  
Author(s):  
Guangwen Li ◽  
Bei Chang ◽  
Hui Li ◽  
Rui Wang ◽  
Gang Li
Keyword(s):  
Human Resources ◽  
Emergency Response ◽  
Mass Casualties ◽  
The Novel ◽  
Public Health Emergencies ◽  
The Past ◽  
Emergency Responses ◽  
Novel Coronavirus ◽  
Dental Professionals

Abstract The past 20 years have seen major public health emergencies and natural disasters, including the Severe Acute Respiratory Syndrome outbreak caused by the SARS-associated coronavirus (SARS-CoV) in 2003; the Wenchuan earthquake in 2008; and the novel coronavirus pandemic (COVID-19) of 2019, which caused mass casualties, infections, and panic. These also resulted in complex demands for medical resources and information, and a shortage of human resources for emergency responses. To address the shortage of human resources required for these emergency responses, Chinese dental professionals made useful contributions. From this work, deficiencies in emergency response training and opportunities for the expansion of rescue capabilities were identified, and relevant recommendations made.

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