scholarly journals Fighting COVID-19

2020 ◽  
Vol 80 (3) ◽  
pp. 698-701 ◽  
Author(s):  
D. M. O. Campos ◽  
C. B. S. Oliveira ◽  
J. M. A. Andrade ◽  
J. I. N. Oliveira
Keyword(s):  
Drug Targets ◽  
Vaccine Development ◽  
High Rate ◽  
The Novel ◽  
Rate Of Spread ◽  
Specific Effects ◽  
Main Protease ◽  
Clinical Strategies ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

Abstract The current COVID-19 pandemic caused by the novel coronavirus (SARS-CoV2) poses a threat to global health owing to its high rate of spread and severe forms of respiratory infection. The lack of vaccines and antivirals prevents clinical strategies against the disease, creating an emerging need for the development of safe and effective treatments. Strategies for vaccine development include complete vaccines against viruses, subunits, and nucleic acids, but are still in their early stages. Studies carried out to date on possible SARS-CoV2 drug targets highlight glycoprotein S, Mpro (main protease or protease type 3C), and a member of the transmembrane serine protease II families (TMPRSS2). However, due to the pandemic state, priority is given to marketed drugs. These include chloroquine (CQ), hydroxychloroquine (HCQ), nitazoxanide, remdesivir, Lopinavir/ritonavir (LPV / r), in addition to treatment with convalescent plasma. But, therapeutic specific effects against SARS-CoV2 have not yet been verified. Most of the information obtained about treatment is based on preliminary and limited studies. We conclude that, at this time of emergency, the search for new therapies is more urgent due to the need to save lives. Thus, we point out as interesting targets for future more specific research: glycoprotein S, Mpro, and TMPRSS2.

Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

2020 ◽  
Author(s):  
Micael Davi Lima de Oliveira ◽  
Kelson Mota Teixeira de Oliveira
Keyword(s):  
World Health Organisation ◽  
World Health ◽  
Lung Cells ◽  
The Novel ◽  
High Modulation ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Viral Receptors ◽  
Theoretical Results

According to the World Health Organisation, until 16 June, 2020, the number of confirmed and notified cases of COVID-19 has already exceeded 7.9 million with approximately 434 thousand deaths worldwide. This research aimed to find repurposing antagonists, that may inhibit the activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as partially modulate the ACE2 receptors largely found in lung cells, and reduce viral replication by inhibiting Nsp12 RNA polymerase. Docking molecular simulations were performed among a total of 60 structures, most of all, published in the literature against the novel coronavirus. The theoretical results indicated that, in comparative terms, paritaprevir, ivermectin, ledipasvir, and simeprevir, are among the most theoretical promising drugs in remission of symptoms from the disease. Furthermore, also corroborate indinavir to the high modulation in viral receptors. The second group of promising drugs includes remdesivir and azithromycin. The repurposing drugs HCQ and chloroquine were not effective in comparative terms to other drugs, as monotherapies, against SARS-CoV-2 infection.

scholarly journals Quinoline and Quinazoline Alkaloids against COVID-19: An In Silico Multitarget Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Esraa M. O. A. Ismail ◽  
Shaza W. Shantier ◽  
Mona S. Mohammed ◽  
Hassan H. Musa ◽  
Wadah Osman ◽  
...  
Keyword(s):  
Antimalarial Activity ◽  
The Novel ◽  
Socioeconomic Impacts ◽  
Health Crisis ◽  
Natural Sources ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Protease ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Potential Inhibitors

The recent outbreak of the highly contagious coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 has created a global health crisis with socioeconomic impacts. Although, recently, vaccines have been approved for the prevention of COVID-19, there is still an urgent need for the discovery of more efficacious and safer drugs especially from natural sources. In this study, a number of quinoline and quinazoline alkaloids with antiviral and/or antimalarial activity were virtually screened against three potential targets for the development of drugs against COVID-19. Among seventy-one tested compounds, twenty-three were selected for molecular docking based on their pharmacokinetic and toxicity profiles. The results identified a number of potential inhibitors. Three of them, namely, norquinadoline A, deoxytryptoquivaline, and deoxynortryptoquivaline, showed strong binding to the three targets, SARS-CoV-2 main protease, spike glycoprotein, and human angiotensin-converting enzyme 2. These alkaloids therefore have promise for being further investigated as possible multitarget drugs against COVID-19.

scholarly journals SARS-CoV-2: preliminary study of infected human nasopharyngeal tissue by high resolution microscopy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Brian Mondeja ◽  
Odalys Valdes ◽  
Sonia Resik ◽  
Ananayla Vizcaino ◽  
Emilio Acosta ◽  
...  
Keyword(s):  
High Resolution ◽  
Control Sample ◽  
Negative Control ◽  
High Rate ◽  
Apical Region ◽  
The Novel ◽  
Rt Pcr ◽  
Crown Shape ◽  
Novel Coronavirus ◽  
High Resolution Microscopy

Abstract Background The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published. Methods Nasopharyngeal swabs were collected from 12 Cuban individuals, six asymptomatic and RT-PCR negative (negative control) and six others from a COVID-19 symptomatic and RT-PCR positive for SARS CoV-2. Samples were treated with an aldehyde solution and processed by scanning electron microscopy (SEM), confocal microscopy (CM) and, atomic force microscopy. Improvement and segmentation of coronavirus images were performed by a novel mathematical image enhancement algorithm. Results The images of the negative control sample showed the characteristic healthy microvilli morphology at the apical region of the nasal epithelial cells. As expected, they do not display virus-like structures. The images of the positive sample showed characteristic coronavirus-like particles and evident destruction of microvilli. In some regions, virions budding through the cell membrane were observed. Microvilli destruction could explain the anosmia reported by some patients. Virus-particles emerging from the cell-surface with a variable size ranging from 80 to 400 nm were observed by SEM. Viral antigen was identified in the apical cells zone by CM. Conclusions The integral microscopy study showed that SARS-CoV-2 has a similar image to SARS-CoV. The application of several high-resolution microscopy techniques to nasopharyngeal samples awaits future use.

Biochemical and Biophysical characterization of the main protease, 3-chymotrypsin-like protease (3CLpro), from the novel coronavirus disease 19 (COVID-19)

2020 ◽  
Author(s):  
Juliana C. Ferreira ◽  
Wael M. Rabeh
Keyword(s):  
Antiviral Drug ◽  
Analytical Techniques ◽  
The Novel ◽  
Buffer Solution ◽  
Biophysical Characterization ◽  
Main Protease ◽  
Wide Ph Range ◽  
The Stability ◽  
Ph Range ◽  
Novel Coronavirus

Abstract Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the novel coronavirus disease 2019 (COVID-19). An appealing antiviral drug target is the coronavirus 3C-like protease (3CLpro) that is responsible for the processing of the viral polyproteins and liberation of functional proteins essential for the maturation and infectivity of the virus. In this study, multiple thermal analytical techniques have been implemented to acquire the thermodynamic parameters of 3CLpro at different buffer conditions. 3CLpro exhibited relatively high thermodynamic stabilities over a wide pH range; however, the protease was found to be less stable in the presence of salts. Divalent metal cations reduced the thermodynamic stability of 3CLpro more than monovalent cations; however, altering the ionic strength of the buffer solution did not alter the stability of 3CLpro. Furthermore, the most stable thermal kinetic stability of 3CLpro was recorded at pH 7.5, with the highest enthalpy of activation calculated from the slope of Eyring plot. The biochemical and biophysical properties of 3CLpro explored here will improve the solubility and stability of 3CLpro for optimum conditions for the setup of an enzymatic assay for the screening of inhibitors to be used as lead candidates in the drug discovery and antiviral design for therapeutics against COVID-19.

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 SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 231 ◽  
Author(s):  
Firas A. Rabi ◽  
Mazhar S. Al Zoubi ◽  
Ghena A. Kasasbeh ◽  
Dunia M. Salameh ◽  
Amjad D. Al-Nasser
Keyword(s):  
Vaccine Development ◽  
Current Knowledge ◽  
Treatment Options ◽  
The Novel ◽  
Clinical Criteria ◽  
Health Authorities ◽  
Close Relationship ◽  
Public Health Authorities ◽  
Molecular Information ◽  
Novel Coronavirus

In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes.

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

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.

scholarly journals X-ray Structure of Main Protease of the Novel Coronavirus SARS-CoV-2 Enables Design of α-Ketoamide Inhibitors

2020 ◽  
Author(s):  
Linlin Zhang ◽  
Daizong Lin ◽  
Xinyuanyuan Sun ◽  
Katharina Rox ◽  
Rolf Hilgenfeld
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Atypical Pneumonia ◽  
The Novel ◽  
Replication Complex ◽  
X Ray ◽  
Main Protease ◽  
Pharmacokinetic Properties ◽  
Novel Coronavirus ◽  
Further Development

AbstractA novel coronavirus has been identified as the causative agent of a massive outbreak of atypical pneumonia originating at Wuhan, Hubei province, China. Involved in the formation of the coronavirus replication complex, the viral main protease (Mpro, also called 3CLpro) represents an attractive target for therapy. We determined the crystal structure of the unliganded Mpro at 1.75 Å resolution and used this structure to guide optimization of a series of alpha-ketoamide inhibitors. The main goal of the optimization efforts was improvement of the pharmacokinetic properties of the compounds. We further describe 1.95- and 2.20-Å crystal structures of the complex between the enzyme and the most potent alpha-ketoamide optimized this way. These structures will form the basis for further development of these compounds to antiviral drugs.

scholarly journals Microbes, Clinical trials, Drug Discovery, and Vaccine Development: The Current Perspectives

2021 ◽  
Vol 4 (4) ◽  
pp. 311-323
Author(s):  
Venkataramana Kandi ◽  
Tarun Kumar Suvvari ◽  
Sabitha Vadakedath ◽  
Vikram Godishala
Keyword(s):  
Drug Discovery ◽  
Genetic Variants ◽  
Vaccine Development ◽  
Treatment Options ◽  
Morbidity And Mortality ◽  
Therapeutic Interventions ◽  
Multi Drug Resistance ◽  
The Novel ◽  
Normal Human ◽  
Novel Coronavirus

Because of the frequent emergence of novel microbial species and the re-emergence of genetic variants of hitherto known microbes, the global healthcare system, and human health has been thrown into jeopardy. Also, certain microbes that possess the ability to develop multi-drug resistance (MDR) have limited the treatment options in cases of serious infections, and increased hospital and treatment costs, and associated morbidity and mortality. The recent discovery of the novel Coronavirus (n-CoV), the Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2) that is causing the CoV Disease-19 (COVID-19) has resulted in severe morbidity and mortality throughout the world affecting normal human lives. The major concern with the current pandemic is the non-availability of specific drugs and an incomplete understanding of the pathobiology of the virus. It is therefore important for pharmaceutical establishments to envisage the discovery of therapeutic interventions and potential vaccines against the novel and MDR microbes. Therefore, this review is attempted to update and explore the current perspectives in microbes, clinical research, drug discovery, and vaccine development to effectively combat the emerging novel and re-emerging genetic variants of microbes.

scholarly journals Epidemiological Features of the Incidence of COVID-19 in Moscow in the Period from March 1 to August 31, 2020

2021 ◽  
pp. 57-62
Author(s):  
AV Ivanenko ◽  
DV Soloviev ◽  
NA Volkova ◽  
VM Glinenko ◽  
OA Smirnova ◽  
...  
Keyword(s):  
Statistical Significance ◽  
High Rate ◽  
The Novel ◽  
Upper Respiratory Tract ◽  
Epidemiological Features ◽  
Student’S T ◽  
Novel Coronavirus ◽  
Tract Infections ◽  
The City ◽  
Spearman’S Correlation

Introduction: Coronavirus (SARS-CoV-2) infection is a global healthcare and social problem due to a rapid ubiquitous spread of the virus, a high rate of complications and deaths. The disease is often asymptomatic, which can contribute to its spread, while the most common complication is the development of pneumonia with or without acute respiratory failure and respiratory distress syndrome, which are often fatal. These characteristics of the disease, along with the almost complete lack of immunity in the population around the world (before the mass spread), allowed SARS-CoV-2 to spread freely among the population of all countries. Our objective was to assess the epidemiological features of the incidence of the novel coronavirus disease (COVID-19) in the population of the city of Moscow. Materials and methods: We conducted a retrospective analysis of all confirmed COVID-19 cases, the total number of diagnostic tests for COVID-19, and the incidence of upper respiratory tract infections registered in Moscow from March 1 to August 31, 2020. The correlation analysis was performed by calculating the Spearman’s correlation coefficient and subsequent statistical significance of differences in the compared relative values (p) from the Student’s t-test. Confidence intervals were determined with the calculation of average errors of the compared variables – m(σ). Conclusion: The revealed features of the COVID-19 incidence in Moscow help establish the factors influencing the development of the epidemic process in the city and give an accurate prediction of the COVID-19 situation for the future.

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