scholarly journals Reaction Cycles of Halogen Species in the Immune Defense: Implications for Human Health and Diseases and the Pathology and Treatment of COVID-19

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1461
Author(s):  
Qing-Bin Lu
Keyword(s):  
Human Health ◽  
Cell Metabolism ◽  
Antiviral Treatment ◽  
Drug Repurposing ◽  
Immune Defense ◽  
Signaling Molecule ◽  
Global Pandemic ◽  
No Signaling ◽  
Reaction Cycles ◽  
Protective Signaling

There is no vaccine or specific antiviral treatment for COVID-19, which is causing a global pandemic. One current focus is drug repurposing research, but those drugs have limited therapeutic efficacies and known adverse effects. The pathology of COVID-19 is essentially unknown. Without this understanding, it is challenging to discover a successful treatment to be approved for clinical use. This paper addresses several key biological processes of reactive oxygen, halogen and nitrogen species (ROS, RHS and RNS) that play crucial physiological roles in organisms from plants to humans. These include why superoxide dismutases, the enzymes to catalyze the formation of H2O2, are required for protecting ROS-induced injury in cell metabolism, why the amount of ROS/RNS produced by ionizing radiation at clinically relevant doses is ~1000 fold lower than the endogenous ROS/RNS level routinely produced in the cell and why a low level of endogenous RHS plays a crucial role in phagocytosis for immune defense. Herein we propose a plausible amplification mechanism in immune defense: ozone-depleting-like halogen cyclic reactions enhancing RHS effects are responsible for all the mentioned physiological functions, which are activated by H2O2 and deactivated by NO signaling molecule. Our results show that the reaction cycles can be repeated thousands of times and amplify the RHS pathogen-killing (defense) effects by 100,000 fold in phagocytosis, resembling the cyclic ozone-depleting reactions in the stratosphere. It is unraveled that H2O2 is a required protective signaling molecule (angel) in the defense system for human health and its dysfunction can cause many diseases or conditions such as autoimmune disorders, aging and cancer. We also identify a class of potent drugs for effective treatment of invading pathogens such as HIV and SARS-CoV-2 (COVID-19), cancer and other diseases, and provide a molecular mechanism of action of the drugs or candidates.

COVID-19 Global Pandemic Fight by Drugs: A Mini-Review on Hope and Hype

2021 ◽  
Vol 18 ◽  
Author(s):  
Sunil Tekale ◽  
Vishnu Gore ◽  
Pravin Kendrekar ◽  
Shivaji Thore ◽  
László Kótai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Transmission Rate ◽  
Antiviral Treatment ◽  
Drug Repurposing ◽  
Current Medical ◽  
Medical Emergency ◽  
Global Pandemic ◽  
Global Issue ◽  
The City

: Coronavirus disease 2019 (Covid-19) is caused by the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) was firstly identified in the city of Wuhan of China in December 2019, which was spread and become a global issue due to its high transmission rate. To date, the outbreak of COVID-19 has resulted in infection to 150,356,672 people and the death of 3,167,010 patients. It paralyzed the economy of all the countries worldwide. Unfortunately, no specific FDA-approved antiviral treatment or vaccine is available to curb the outbreak. Considering the possible mutations of SARS-CoV-2, the current medical emergency required a longer time for drug design and vaccine development. Drug repurposing is a promising option for potent therapeutic against the pandemic. The present review encompasses various drugs or appropriate combinations of already FDA-approved antimalarial, antiviral, anticancer, anti-inflammatory, and antibiotic therapeutic candidates for use in the clinical trials as a ray of hope against COVID-19. It is expected to deliver better clinical and laboratory outcomes of drugs as a prevention strategy for the eradication of the disease.

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

scholarly journals Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

2021 ◽  
Vol 14 (3) ◽  
pp. 217
Author(s):  
Jiri Patocka ◽  
Kamil Kuca ◽  
Patrik Oleksak ◽  
Eugenie Nepovimova ◽  
Martin Valis ◽  
...  
Keyword(s):  
Literature Review ◽  
Human Health ◽  
World Economy ◽  
Web Of Science ◽  
Drug Repurposing ◽  
Final Analysis ◽  
High Rate ◽  
Suitable Candidate ◽  
Promising Strategy ◽  
The World

Since December 2019, SARS-CoV-2 (COVID-19) has been a worldwide pandemic with enormous consequences for human health and the world economy. Remdesivir is the only drug in the world that has been approved for the treating of COVID-19. This drug, as well as vaccination, still has uncertain effectiveness. Drug repurposing could be a promising strategy how to find an appropriate molecule: rapamycin could be one of them. The authors performed a systematic literature review of available studies on the research describing rapamycin in association with COVID-19 infection. Only peer-reviewed English-written articles from the world’s acknowledged databases Web of Science, PubMed, Springer and Scopus were involved. Five articles were eventually included in the final analysis. The findings indicate that rapamycin seems to be a suitable candidate for drug repurposing. In addition, it may represent a better candidate for COVID-19 therapy than commonly tested antivirals. It is also likely that its efficiency will not be reduced by the high rate of viral RNA mutation.

scholarly journals Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3213
Author(s):  
Alon Ben David ◽  
Eran Diamant ◽  
Eyal Dor ◽  
Ada Barnea ◽  
Niva Natan ◽  
...  
Keyword(s):  
Receptor Binding ◽  
High Throughput Screening ◽  
Cell Attachment ◽  
Drug Repurposing ◽  
Heparin Sodium ◽  
Compound Libraries ◽  
Global Pandemic ◽  
Ic50 Values ◽  
Binding Inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy. Here, we describe the development of an in vitro RBD-ACE2 binding assay and its application to identify inhibitors of the interaction of the SARS-CoV-2 RBD to ACE2 by the high-throughput screening of two compound libraries (LOPAC®1280 and DiscoveryProbeTM). Three compounds, heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid, were found to exert an effective binding inhibition, with IC50 values ranging from 0.6 to 5.5 µg/mL. A plaque reduction assay in Vero E6 cells infected with a SARS-CoV-2 surrogate virus confirmed the inhibition efficacy of heparin sodium and ATA. Molecular docking analysis located potential binding sites of these compounds in the RBD. In light of these findings, the screening system described herein can be applied to other drug libraries to discover potent SARS-CoV-2 inhibitors.

PAK1 is a novel cardiac protective signaling molecule

2014 ◽  
Vol 8 (4) ◽  
pp. 399-403 ◽  
Author(s):  
Yunbo Ke ◽  
Xin Wang ◽  
Xu Yu Jin ◽  
R. John Solaro ◽  
Ming Lei
Keyword(s):  
Signaling Molecule ◽  
Protective Signaling

scholarly journals Main Protease Inhibitors and Drug Surface Hotspot for the Treatment of COVID-19: Drug Repurposing and Molecular Docking Approach

2020 ◽  
Author(s):  
Mahmudul Hasan ◽  
Md Sorwer Alam Parvez ◽  
Kazi Faizul Azim ◽  
Abdus Shukur Imran ◽  
Topu Raihan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Repurposing ◽  
Pharmacokinetic Parameters ◽  
The Novel ◽  
Drug Candidates ◽  
Target Drug ◽  
Global Pandemic ◽  
Main Protease ◽  
Docking Approach ◽  
Repurposed Drugs

<div>The world is facing an unprecedented global pandemic caused by the novel SARS-CoV-2. In the absence</div><div>of a specific therapeutic agent to treat COVID-19 patients, the present study aimed to virtually screen out</div><div>the effective drug candidates from the approved main protease protein (MPP) inhibitors and their</div><div>derivatives for the treatment of SARS-CoV-2. Here, drug repurposing and molecular docking were</div><div>employed to screen approved MPP inhibitors and their derivatives. The approved MPP inhibitors against</div><div>HIV and HCV were prioritized, whilst hydroxychloroquine, favipiravir, remdesivir, and alpha-ketoamide</div><div>were studied as control. The target drug surface hotspot was also investigated through the molecular</div><div>docking technique. ADME analysis was conducted to understand the pharmacokinetics and drug-likeness</div><div>of the screened MPP inhibitors. The result of this study revealed that Paritaprevir (-10.9 kcal/mol), and its</div><div>analog (CID 131982844)(-16.3 kcal/mol) showed better binding affinity than the approved MPP inhibitor</div><div>compared in this study including favipiravir, remdesivir, and alpha-ketoamide. A comparative study among</div><div>the screened putative MPP inhibitors revealed that amino acids T25, T26, H41, M49, L141, N142, G143,</div><div>C145, H164, M165, E166, D187, R188, and Q189 are at critical positions for becoming the surface hotspot</div><div>in the MPP of SARS-CoV-2. The study also suggested that paritaprevir and its' analog (CID 131982844),</div><div>may be effective against SARS-CoV-2 as these molecules had the common drug-surface hotspots on the</div><div>main protease protein of SARS-CoV-2. Other pharmacokinetic parameters also indicate that paritaprevir</div><div>and its top analog (CID 131982844) will be either similar or better-repurposed drugs than already approved</div><div>MPP inhibitors. </div><div><br></div>

scholarly journals Coronavirus Disease 2019 (COVID-19): Origin, Impact, and Drug Development

2021 ◽  
Author(s):  
Amaresh Mishra ◽  
Nisha Nair ◽  
Amit K. Yadav ◽  
Pratima Solanki ◽  
Jaseela Majeed ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Therapeutic Option ◽  
Treatment Strategies ◽  
Drug Repurposing ◽  
Cost Effective ◽  
High Sequence Identity ◽  
Drug Candidates ◽  
Global Pandemic ◽  
The People ◽  
Health Organization

At the end of December 2019, in Wuhan, China, a rapidly spreading unknown virus was reported to have caused coronavirus disease of 2019 (COVID-19). Origin linked to Wuhan’s wholesale food market where live animals are sold. This disease is caused by SARS Coronavirus-2 (SARS-CoV-2), which is closely related to the Severe Acute Respiratory Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This virus shares a high sequence identity with bat-derived SARS-like Coronavirus, which indicating its zoonotic origin. The virus spread globally, provoking widespread attention and panic. This Coronavirus is highly pathogenic and causes mild to severe respiratory disorders. Later, it was declared a global pandemic by the World Health Organization (WHO) due to its highly infectious nature and worldwide mortality rate. This virus is a single-stranded, positive-sense RNA genome, and its genome length about 26 to 32 kb that infects a broad range of vertebrates. The researchers worldwide focus on establishing treatment strategies on drug and vaccine development to prevent this COVID-19 pandemic. A drug repurposing approach has been used to identify a rapid treatment for the people affected by COVID-19, which could be cost-effective and bypass some Food and Drug Association (FDA) regulations to move quickly in phase-3 trials. However, there is no promising therapeutic option available yet. This book chapter addresses current information about the COVID-19 disease, including its origins, impacts, and the novel potential drug candidates that can help treat the COVID-19.

scholarly journals Automatic Identification of SARS Coronavirus using Compression-Complexity Measures

2020 ◽  
Author(s):  
Karthi Balasubramanian ◽  
Nithin Nagaraj
Keyword(s):  
Distance Measure ◽  
Antiviral Treatment ◽  
Nucleotide Sequences ◽  
Automatic Identification ◽  
Sars Coronavirus ◽  
Complexity Measures ◽  
Medical Practitioners ◽  
Global Pandemic ◽  
Institute Of Technology ◽  
Main Ideas

AbstractFinding vaccine or specific antiviral treatment for global pandemic of virus diseases (such as the ongoing COVID-19) requires rapid analysis, annotation and evaluation of metagenomic libraries to enable a quick and efficient screening of nucleotide sequences. Traditional sequence alignment methods are not suitable and there is a need for fast alignment-free techniques for sequence analysis. Information theory and data compression algorithms provide a rich set of mathematical and computational tools to capture essential patterns in biological sequences. In 2013, our research group (Nagaraj et al., Eur. Phys. J. Special Topics 222(3-4), 2013) has proposed a novel measure known as Effort-To-Compress (ETC) based on the notion of compression-complexity to capture the information content of sequences. In this study, we propose a compression-complexity based distance measure for automatic identification of SARS coronavirus strains from a set of viruses using only short fragments of nucleotide sequences. We also demonstrate that our proposed method can correctly distinguish SARS-CoV-2 from SARS-CoV-1 viruses by analyzing very short segments of nucleotide sequences. This work could be extended further to enable medical practitioners in automatically identifying and characterizing SARS coronavirus strain in a fast and efficient fashion using short and/or incomplete segments of nucleotide sequences. Potentially, the need for sequence assembly can be circumvented.NoteThe main ideas and results of this research were first presented at the International Conference on Nonlinear Systems and Dynamics (CNSD-2013) held at Indian Institute of Technology, Indore, December 12, 2013. In this manuscript, we have extended our preliminary analysis to include SARS-CoV-2 virus as well.

scholarly journals The impact of natural disasters on the spread of COVID-19: a geospatial, agent-based epidemiology model

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Maximillian Van Wyk de Vries ◽  
Lekaashree Rambabu
Keyword(s):  
Infectious Diseases ◽  
Natural Disasters ◽  
Human Health ◽  
Natural Disaster ◽  
Potential Effect ◽  
Agent Based ◽  
Median Increase ◽  
Global Pandemic ◽  
Disaster Scenario ◽  
The Impact

Abstract Background Natural disasters and infectious diseases result in widespread disruption to human health and livelihood. At the scale of a global pandemic, the co-occurrence of natural disasters is inevitable. However, the impact of natural disasters on the spread of COVID-19 has not been extensively evaluated through epidemiological modelling. Methods We create an agent-based epidemiology model based on COVID-19 clinical, epidemiological, and geographic data. We first model 35 scenarios with varying natural disaster timing and duration for a COVID-19 outbreak in a theoretical region. We then evaluate the potential effect of an eruption of Vesuvius volcano on the spread of COVID-19 in Campania, Italy. Results In a majority of cases, the occurrence of a natural disaster increases the number of disease related fatalities. For a natural disaster fifty days after infection onset, the median increase in fatalities is 2, 59, and 180% for a 2, 14, and 31-day long natural disaster respectively, when compared to the no natural disaster scenario. For the Campania case, the median increase in fatalities is 1.1 and 2.4 additional fatalities per 100,000 for eruptions on day 1 and 100 respectively, and 60.0 additional fatalities per 100,000 for an eruption close to the peak in infections (day 50). Conclusion Our results show that the occurrence of a natural disaster in most cases leads to an increase in infection related fatalities, with wide variance in possible outcomes depending on the timing of the natural disaster relative to the peak in infections and the duration of the natural disaster.

scholarly journals Integrated Docking and Enhanced Sampling Based Selection of Repurposing Drugs for SARS-CoV-2 by Targeting Host Dependent Factors

2020 ◽  
Author(s):  
Amit Kumawat ◽  
Sadanandam Namsani ◽  
Debabrata Pramanik ◽  
Sudip Roy ◽  
Jayant K. Singh
Keyword(s):  
Regulatory Protein ◽  
Drug Repurposing ◽  
Md Simulations ◽  
Free Energy Calculations ◽  
High Throughput Analysis ◽  
Drug Candidates ◽  
Global Pandemic ◽  
Therapeutic Uses ◽  
Approved Drugs ◽  
Fda Approved Drugs

Since the onset of global pandemic, the most focused research currently in progress is the development of vaccine candidates and clinical trials of existing FDA approved drugs for other relevant diseases, in order to repurpose them for the COVID-19. Here, we investigate the drug repurposing strategies to counteract the coronavirus infection which involves several potential targetable host proteins involved in viral replication and disease progression. We report the high throughput analysis of literature-derived repurposing drug candidates that can be used to target the genetic regulators known to interact with viral proteins based on experimental and interactome studies. In this work we have performed integrated molecular docking followed by molecular dynamics (MD) simulations and free energy calculations through an expedite insilico process where the number of screened candidates reduces sequentially at every step based on physicochemical information. We elucidate that in addition to the pre-clinical and FDA approved drugs that targets specific regulatory proteins, a range of chemical compounds (Nafamostat, Chloramphenicol, Ponatinib) binds to the other gene transcription and translation regulatory protein with higher affinity and may harbour potential for therapeutic uses.<br>

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