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

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.

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Screening of Kabasura Kudineer Chooranam against COVID-19 through Targeting of Main Protease and RNA-Dependent RNA Polymerase of SARS-CoV-2 by Molecular Docking Studies

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2020.ajomc-p299 ◽

2020 ◽

Vol 5 (4) ◽

pp. 319-331

Author(s):

K. Gopalasatheeskumar ◽

Karthikeyen Lakshmanan ◽

Anguraj Moulishankar ◽

Jerad Suresh ◽

D. Kumuthaveni Babu ◽

...

Keyword(s):

Molecular Docking ◽

Rna Polymerase ◽

Docking Studies ◽

The Novel ◽

Rna Dependent Rna Polymerase ◽

Molecular Docking Studies ◽

Main Protease ◽

Short Span ◽

Novel Coronavirus

COVID-19 is the infectious pandemic disease caused by the novel coronavirus. The COVID-19 is spread globally in a short span of time. The Ministry of AYUSH, India which promotes Siddha and other Indian system of medicine recommends the use of formulation like Nilavembu Kudineer and Kaba Sura Kudineer Chooranam (KSKC). The present work seeks to provide the evidence for the action of 74 different constituents of the KSKC formulation acting on two critical targets. That is main protease and SARS-CoV-2 RNAdependent RNA polymerase target through molecular docking studies. The molecular docking was done by using AutoDock Tools 1.5.6 of the 74 compounds, about 50 compounds yielded docking results against COVID-19 main protease while 42 compounds yielded against SARSCoV- 2 RNA-dependent RNA polymerase. This research has concluded that the KSKC has the lead molecules that inhibits COVID-19’s target of main protease of COVID-19 and SARS-CoV-2 RNA-dependent RNA polymerase.

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Antiviral potential of phytoligands against chymotrypsin-like protease of COVID‐19 virus using molecular docking studies: An optimistic approach

10.21203/rs.3.rs-23956/v1 ◽

2020 ◽

Author(s):

Ratish Chandra Mishra ◽

Rosy Kumari ◽

Shivani Yadav ◽

Jaya Parkash Yadav

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Drug Repositioning ◽

Docking Studies ◽

The Novel ◽

Lead Compounds ◽

Recent Outbreak ◽

Novel Coronavirus ◽

The City ◽

Ucsf Chimera

Abstract A recent outbreak of the novel coronavirus, COVID‐19, in the city of Wuhan, Hubei province, China and its ensuing worldwide spread have resulted in lakhs of infections and thousands of deaths. As of now, there are no registered therapies for treating the contagious COVID‐19 infections, henceforth drug repositioning may provide a fast way out. In the present study, a total of thirty-five compounds including commonly used anti-viral drugs were screened against chymotrypsin-like protease (3CLpro) using SwissDock. Interaction between amino acid of targeted protein and ligands was visualized by UCSF Chimera. Docking studies revealed that the phytochemicals such as cordifolin, anisofolin A, apigenin 7-glucoside, luteolin, laballenic acid, quercetin, luteolin-4-glucoside exhibited significant binding energy with the enzyme viz. - 8.77, -8.72, -8.36, -8.35, -8.13, -8.04 and -7.87 Kcal/Mol respectively. Therefore, new lead compounds can be used for drug development against SARS‐CoV‐2 infections.

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Political Ideology and the Outbreak of COVID-19 in the United States

10.31234/osf.io/jrpfd ◽

2020 ◽

Author(s):

Daniel L. Rosenfeld

Keyword(s):

United States ◽

Political Ideology ◽

State Level ◽

The United States ◽

The State ◽

The Novel ◽

Unique Role ◽

Rapid Spread ◽

Novel Coronavirus

At the state level within the United States, did political ideology predict the outbreak of the novel coronavirus (COVID-19)? Throughout March 2020, the United States became the epicenter of the COVID-19 pandemic, recording the most cases of any country worldwide. The current research found that, at the state level within the United States, more conservative political ideology predicted delayed implementation of stay-at-home orders and more rapid spread of COVID-19. Effects were significant across two distinct operationalizations of political ideology and held over and above relevant covariates, suggesting a potentially unique role of political ideology in the United States’ COVID-19 outbreak. Considering political ideological factors may offer valuable insights into epidemiological processes surrounding COVID-19.

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

10.26434/chemrxiv.11938173.v9 ◽

2020 ◽

Cited By ~ 7

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

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.

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COVID-19: A natural phenomena or laboratory-based origin?

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v19i0.48197 ◽

2020 ◽

Author(s):

Fanila Shahzad ◽

Md Talat Nasim

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Medical Science ◽

Health Concern ◽

The Novel ◽

Natural Phenomena ◽

Viral Reservoirs ◽

Major Health ◽

Novel Virus ◽

Novel Coronavirus ◽

Insight Into

The novel coronavirus, otherwise known as COVID-19 has fast become a major health concern. The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV‐ 2) is the third coronavirus outbreak, following severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses. Since the initial cases of a pneumonia of unknown aetiology, which was later identified as COVID-19 in Wuhan, Hubei province, China, there has been much debate and speculation regarding the origins of this novel virus. This review aims to provide an insight into the origin of SARS-CoV-2 by reflecting on genomic data gathered thus far. Identifying the origins of SARS-CoV-2 can lead to better understanding of hidden viral reservoirs that may exist and pose a threat to society as well as allow greater understanding of the mechanisms by which these viruses have successfully achieved cross species transmission. Greater knowledge in regard to this can lead to the development of strategies which can aid in preventing future outbreaks of this scale. Bangladesh Journal of Medical Science Vol.19(0) 2020 p. p. S 85-S 87

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Evaluation of Lens culinaris phytochemicals in binding to the 3C-like protease of SARS-CoV-2 – A molecular docking approach

Indian Journal of Medical Sciences ◽

10.25259/ijms_219_2020 ◽

2020 ◽

Vol 72 ◽

pp. 173-176

Author(s):

Anamul Hasan ◽

Rownak Jahan ◽

Khoshnur Jannat ◽

Tohmina Afroze Bondhon ◽

Md Shahadat Hossan ◽

...

Keyword(s):

Molecular Docking ◽

Lens Culinaris ◽

Docking Studies ◽

Polyphenolic Compounds ◽

Binding Affinities ◽

The Novel ◽

Molecular Docking Studies ◽

Docking Approach ◽

Novel Coronavirus ◽

Scientific Attention

The novel coronavirus known as SARS-CoV-2 and the virus-induced disease COVID-19 has caused widespread concerns due to its contagiousness, fatality rate, and the absence of drug(s). This study investigated Lens culinaris and its phytochemicals, especially the flavonoids. The compounds were assessed through molecular docking studies for their binding abilities with the major protease of the novel coronavirus, SARS-CoV-2 (PDB: 6LU7). A total of 42 phytochemicals of Lens culinaris were analyzed through molecular docking studies for their binding affinities to COVID 3C-like protease. Of them, 23 compounds were found to have binding affinities to the protease of −7.5 kcal/mol or higher. Our study indicates that Lens culinaris contains a number of polyphenolic compounds as well as phytosterols, which can bind to the active site of the protease, and so merits further scientific attention on trials for use as potential anti-COVID-19 drugs.

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Death in the Line of Duty: Caregivers in the Plague narratives

Rupkatha Journal on Interdisciplinary Studies in Humanities ◽

10.21659/rupkatha.v12n5.rioc1s25n4 ◽

2020 ◽

Vol 12 (5) ◽

Author(s):

Seema Sinha ◽

Keyword(s):

Professional Ethics ◽

The Other ◽

Close Reading ◽

The Novel ◽

History Record ◽

The Face ◽

Novel Coronavirus ◽

Insight Into

The dystopian tropes in the plague narratives shift our gaze from the presence of professional ethics to the Gothic horror that unfolds subsequently. Yet whether it is the Great Plague of London in the year 1665, or the Novel Coronavirus in Mumbai in the year 2020, the rampant spread of the contagion and the associated dread bring into focus the selflessness of the caregivers, namely, the medical and the para-medic staff. Comparing the occurrences, one historical, the other still unfolding, this study examines the eery similarities that delineate contagion as metaphor, and the role of doctors in the pandemics. The aim is to find out what happens when the doctors stumble – to succumb to fear, to fall prey to diseases that flesh is subject to, or to violate the oath of Hippocrates. We intend to scrutinize if like soldiers on the battle-front, these frontline warriors also keep their tryst with death in the line of duty, or does History record otherwise. Whether the pestilence be classical or modern, the response of the caregivers is the cornerstone on which any society is grounded. The purpose of this study is to evaluate if courage in the face of disaster is still relevant in this age of anxiety, or does self-preservation win against ethics and morality. A close reading of Daniel Defoe’s A Journal of the Plague Year gives us an insight into the timelessness of such issues, especially in a world that is plagued with maladies of its own making.

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Immune response against SARS-CoV-2 variants: the role of neutralization assays

npj Vaccines ◽

10.1038/s41541-021-00404-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Alicja Maria Chmielewska ◽

Anna Czarnota ◽

Krystyna Bieńkowska-Szewczyk ◽

Katarzyna Grzyb

Keyword(s):

Immune Response ◽

Social Life ◽

Neutralizing Antibody ◽

The Novel ◽

International Scientific Community ◽

Rapid Spread ◽

Cost Efficient ◽

Novel Coronavirus

AbstractSince the emergence of the novel coronavirus SARS-CoV-2 in late 2019, the COVID-19 pandemic has hindered social life and global economic activity. As of July 2021, SARS-CoV-2 has caused over four million deaths. The rapid spread and high mortality of the disease demanded the international scientific community to develop effective vaccines in a matter of months. However, unease about vaccine efficacy has arisen with the spread of the SARS-CoV-2 variants of concern (VOCs). Time- and cost-efficient in vitro neutralization assays are widely used to measure neutralizing antibody responses against VOCs. However, the extent to which in vitro neutralization reflects protection from infection remains unclear. Here, we describe common neutralization assays based on infectious and pseudotyped viruses and evaluate their role in testing neutralizing responses against new SARS-CoV-2 variants. Additionally, we briefly review the recent findings on the immune response elicited by available vaccines against major SARS-CoV-2 variants, including Alpha, Beta, Gamma, and Delta.

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

10.26434/chemrxiv.11938173 ◽

2020 ◽

Cited By ~ 2

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

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.

Download Full-text