Molecular Insights of SARS-CoV-2 Infection and Molecular Treatments

2021 ◽  
Vol 21 ◽  
Author(s):  
Lama Abdurrahman ◽  
Xiaoqian Fang ◽  
Yonghong Zhang
Keyword(s):  
Low Cost ◽  
International Health ◽  
Drug Repurposing ◽  
Antiviral Drugs ◽  
New Drugs ◽  
Research Progress ◽  
Comprehensive Overview ◽  
Molecular Therapeutics ◽  
Short Period ◽  
Wide Scale

: The coronavirus disease emerged in December 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome-related coronavirus 2 (SARS-CoV-2) and its rapid global spread has brought an international health emergency and urgent responses for seeking efficient prevention and therapeutic treatment. This has led to imperative needs for illustration of the molecular pathogenesis of SARS-CoV-2, identification of molecular targets or receptors, and development of antiviral drugs, antibodies, and vaccines. In this study, we investigated the current research progress in combating SARS-CoV-2 infection. Based on the published research findings, we first elucidated, at the molecular level, SARS-CoV-2 viral structures, potential viral host-cell-invasion and pathogenic mechanisms, main virus-induced immune responses, and emerging SARS-CoV-2 variants. We then focused on the main virus- and host-based potential targets, summarized and categorized effective inhibitory molecules based on drug development strategies for COVID-19, that can guide efforts for the identification of new drugs and treatment for this problematic disease. Current research and development of antibodies and vaccines were also introduced and discussed. We concluded that the main virus entry route- SARS-CoV-2 spike protein interaction with ACE2 receptors has played a key role in guiding the development of therapeutic treatments against COVID-19, four main therapeutic strategies may be considered in developing molecular therapeutics, and drug repurposing is likely to be an easy, fast and low-cost approach in such a short period of time with urgent need of antiviral drugs. Additionally, the quick development of antibody and vaccine candidates has yielded promising results, but the wide-scale deployment of safe and effective COVID-19 vaccines remains paramount in solving the pandemic crisis. As new variants of the virus begun to emerge, the efficacy of these vaccines and treatments must be closely evaluated. Finally, we discussed the possible challenges of developing molecular therapeutics for COVID-19 and suggested some potential future efforts. Despite the limited availability of literatures, our attempt in this work to provide a relatively comprehensive overview of current SARS-CoV-2 studies can be helpful for quickly acquiring the key information of COVID-19 and further promoting this important research to control and diminish the pandemic.

Nitro derivatives of quinoline and quinoline N-oxide as low-cost alternative for the treatment of SARS-CoV-2 infection

2020 ◽  
Author(s):  
Letícia Cristina Assis ◽  
Alexandre Alves de Castro ◽  
João Paulo Almirão de Jesus ◽  
Eugenie Nepovimova ◽  
Kamil Kuca ◽  
...  
Keyword(s):  
Transmission Rate ◽  
Low Cost ◽  
Computational Design ◽  
Docking Studies ◽  
Biologically Active ◽  
New Drugs ◽  
Time Space ◽  
Short Period ◽  
Nitro Derivatives ◽  
Derivatives Of

Abstract A new and more aggressive strain of coronavirus, known as SARS-CoV-2, which is highly contagious, has rapidly spread across the planet within a short period of time. Due to its high transmission rate and the significant time–space between infection and manifestation of symptoms, the WHO recently declared this a pandemic. Because of the exponentially growing number of new cases of both infections and deaths, development of new therapeutic options to help fight this pandemic is urgently needed. The target molecules of this study were the nitro derivatives of quinoline and quinoline N-oxide. Computational design at the DFT level, docking studies, and molecular dynamics methods as a well-reasoned strategy will aid in elucidating the fundamental physicochemical properties and molecular functions of a diversity of compounds, directly accelerating the process of discovering new drugs. In this study, we discovered isomers based on the nitro derivatives of quinoline and quinoline N-oxide, which are biologically active compounds and may be low-cost alternatives for the treatment of infections induced by SARS-CoV-2.

scholarly journals Perspectives on Antiviral Drugs Development in the Treatment of COVID-19

2021 ◽  
Vol 4 (1) ◽  
pp. 44-59
Author(s):  
Aura Rusu ◽  
Eliza-Mihaela Arbănaşi ◽  
Ioana-Andreea Lungu ◽  
Octavia-Laura Moldovan
Keyword(s):  
Virtual Screening ◽  
De Novo ◽  
Antiviral Effect ◽  
Clinical Results ◽  
Antiviral Drugs ◽  
New Drugs ◽  
Stages Of Development ◽  
Short Period ◽  
Approved Drugs ◽  
New Compounds

Abstract The main objective of this review is to highlight the urgent development of new antiviral drugs against SARS-CoV-2 in the context of the coronavirus pandemic. Antiviral medication against SARS-CoV-2 comprises only remdesivir as an approved drug. Scientists are making considerable efforts to identify other effective antivirals. Investments into the de novo design of new drugs against the SARS-CoV-2 virus are few. Molnupiravir proved to be effective against the SARS-CoV-2 virus and is very close to approval. Pfizer’s two new compounds (PF-07321332, oral administration and PF-07304814, systemic administration) are in the early stages of development. Two types of methods are preferred to discover new antivirals in a short period. Repositioning of approved drugs for antiviral effect conducted to some clinical results for favipiravir, lopinavir/ritonavir, danoprevir/ritonavir, umifenovir, hydroxychloroquine, camostat and nafamostat. Virtual screening of known molecules’ libraries indicated several compounds that were tested or are being tested in clinical trials. In conclusion, only a few innovative antiviral molecules are in various stages of development. However, the repositioning of many known compounds is being studied, including using virtual screening. The pharmaceutical industry is adapting and reinventing itself so that humanity can face a new pandemic in the future.

scholarly journals Computational evidence for nitro derivatives of quinoline and quinoline N-oxide as low-cost alternative for the treatment of SARS-CoV-2 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Letícia C. Assis ◽  
Alexandre A. de Castro ◽  
João P. A. de Jesus ◽  
Eugenie Nepovimova ◽  
Kamil Kuca ◽  
...  
Keyword(s):  
Transmission Rate ◽  
Low Cost ◽  
Computational Design ◽  
Docking Studies ◽  
Biologically Active ◽  
New Drugs ◽  
Time Space ◽  
Short Period ◽  
Nitro Derivatives ◽  
Derivatives Of

AbstractA new and more aggressive strain of coronavirus, known as SARS-CoV-2, which is highly contagious, has rapidly spread across the planet within a short period of time. Due to its high transmission rate and the significant time–space between infection and manifestation of symptoms, the WHO recently declared this a pandemic. Because of the exponentially growing number of new cases of both infections and deaths, development of new therapeutic options to help fight this pandemic is urgently needed. The target molecules of this study were the nitro derivatives of quinoline and quinoline N-oxide. Computational design at the DFT level, docking studies, and molecular dynamics methods as a well-reasoned strategy will aid in elucidating the fundamental physicochemical properties and molecular functions of a diversity of compounds, directly accelerating the process of discovering new drugs. In this study, we discovered isomers based on the nitro derivatives of quinoline and quinoline N-oxide, which are biologically active compounds and may be low-cost alternatives for the treatment of infections induced by SARS-CoV-2.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

scholarly journals Rapid, large-scale species discovery in hyperdiverse taxa using 1D MinION sequencing

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Amrita Srivathsan ◽  
Emily Hartop ◽  
Jayanthi Puniamoorthy ◽  
Wan Ting Lee ◽  
Sujatha Narayanan Kutty ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Large Scale ◽  
Low Cost ◽  
Small Body ◽  
Small Subset ◽  
Similar Species ◽  
Large Species ◽  
Morphological Examination ◽  
Species Discovery ◽  
Short Period

Abstract Background More than 80% of all animal species remain unknown to science. Most of these species live in the tropics and belong to animal taxa that combine small body size with high specimen abundance and large species richness. For such clades, using morphology for species discovery is slow because large numbers of specimens must be sorted based on detailed microscopic investigations. Fortunately, species discovery could be greatly accelerated if DNA sequences could be used for sorting specimens to species. Morphological verification of such “molecular operational taxonomic units” (mOTUs) could then be based on dissection of a small subset of specimens. However, this approach requires cost-effective and low-tech DNA barcoding techniques because well-equipped, well-funded molecular laboratories are not readily available in many biodiverse countries. Results We here document how MinION sequencing can be used for large-scale species discovery in a specimen- and species-rich taxon like the hyperdiverse fly family Phoridae (Diptera). We sequenced 7059 specimens collected in a single Malaise trap in Kibale National Park, Uganda, over the short period of 8 weeks. We discovered > 650 species which exceeds the number of phorid species currently described for the entire Afrotropical region. The barcodes were obtained using an improved low-cost MinION pipeline that increased the barcoding capacity sevenfold from 500 to 3500 barcodes per flowcell. This was achieved by adopting 1D sequencing, resequencing weak amplicons on a used flowcell, and improving demultiplexing. Comparison with Illumina data revealed that the MinION barcodes were very accurate (99.99% accuracy, 0.46% Ns) and thus yielded very similar species units (match ratio 0.991). Morphological examination of 100 mOTUs also confirmed good congruence with morphology (93% of mOTUs; > 99% of specimens) and revealed that 90% of the putative species belong to the neglected, megadiverse genus Megaselia. We demonstrate for one Megaselia species how the molecular data can guide the description of a new species (Megaselia sepsioides sp. nov.). Conclusions We document that one field site in Africa can be home to an estimated 1000 species of phorids and speculate that the Afrotropical diversity could exceed 200,000 species. We furthermore conclude that low-cost MinION sequencers are very suitable for reliable, rapid, and large-scale species discovery in hyperdiverse taxa. MinION sequencing could quickly reveal the extent of the unknown diversity and is especially suitable for biodiverse countries with limited access to capital-intensive sequencing facilities.

scholarly journals Generation of High-Yield, Functional Oligodendrocytes from a c-myc Immortalized Neural Cell Line, Endowed with Staminal Properties

2021 ◽  
Vol 22 (3) ◽  
pp. 1124
Author(s):  
Mafalda Giovanna Reccia ◽  
Floriana Volpicelli ◽  
Eirkiur Benedikz ◽  
Åsa Fex Svenningsen ◽  
Luca Colucci-D’Amato
Keyword(s):  
Cell Line ◽  
Low Cost ◽  
Neural Cell ◽  
New Drugs ◽  
High Yield ◽  
Time Saving ◽  
Interacting Protein ◽  
Neuronal Marker ◽  
Differentiation Status

Neural stem cells represent a powerful tool to study molecules involved in pathophysiology of Nervous System and to discover new drugs. Although they can be cultured and expanded in vitro as a primary culture, their use is hampered by their heterogeneity and by the cost and time needed for their preparation. Here we report that mes-c-myc A1 cells (A1), a neural cell line, is endowed with staminal properties. Undifferentiated/proliferating and differentiated/non-proliferating A1 cells are able to generate neurospheres (Ns) in which gene expression parallels the original differentiation status. In fact, Ns derived from undifferentiated A1 cells express higher levels of Nestin, Kruppel-like factor 4 (Klf4) and glial fibrillary protein (GFAP), markers of stemness, while those obtained from differentiated A1 cells show higher levels of the neuronal marker beta III tubulin. Interestingly, Ns differentiation, by Epidermal Growth Factors (EGF) and Fibroblast Growth Factor 2 (bFGF) withdrawal, generates oligodendrocytes at high-yield as shown by the expression of markers, Galactosylceramidase (Gal-C) Neuron-Glial antigen 2 (NG2), Receptor-Interacting Protein (RIP) and Myelin Basic Protein (MBP). Finally, upon co-culture, Ns-A1-derived oligodendrocytes cause a redistribution of contactin-associated protein (Caspr/paranodin) protein on neuronal cells, as primary oligodendrocytes cultures, suggesting that they are able to form compact myelin. Thus, Ns-A1-derived oligodendrocytes may represent a time-saving and low-cost tool to study the pathophysiology of oligodendrocytes and to test new drugs.

scholarly journals Repurposing existing drugs for new uses: a cohort study of the frequency of FDA-granted new indication exclusivities since 1997

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Babak Sahragardjoonegani ◽  
Reed F. Beall ◽  
Aaron S. Kesselheim ◽  
Aidan Hollis
Keyword(s):  
Therapeutic Potential ◽  
Drug Repurposing ◽  
Status Quo ◽  
New Drugs ◽  
Generic Entry ◽  
Small Molecule Drugs ◽  
Clinical Investigations ◽  
Fda Approval ◽  
Limited Duration ◽  
Observation Period

Abstract Background Drug repurposing (i.e., finding novel uses for existing drugs) is essential for maximizing medicines’ therapeutic utility, but obtaining regulatory approval for new indications is costly. Policymakers have therefore created temporary indication-specific market exclusivities to incentivize drug innovators to run new clinical investigations. The effectiveness of these exclusivities is poorly understood. Objective To determine whether generic entry impacts the probability of new indication additions. Methods For a cohort of all new small-molecule drugs approved by the FDA between July 1997 and May 2020, we tracked new indications added for the subset of drugs that experienced generic entry during the observation period and then analyzed how the probability of a new indication changed with the number of years since/to generic entry. Results Of the 197 new drugs that subsequently experienced generic entry, only 64 (32%) had at least one new indication added. The probability of a new indication addition peaked above 4% between 7 and 8 years prior to generic entry and then to dropped to near zero 15 years after FDA approval. We show that the limited duration of exclusivity reduces the number of secondary indications significantly. Conclusion Status quo for most drug innovators is creating novel one-indication products. Despite indication-specific exclusivities, the imminence of generic entry still has a detectable impact on reducing the chances of new indication additions. There is much room for improvement when it comes to incentivizing clinical investigations for new uses and unlocking existing medicines’ full therapeutic potential.

scholarly journals Recent Developments of Antimony-Based Anodes for Sodium- and Potassium-Ion Batteries

2021 ◽  
Author(s):  
Bochao Chen ◽  
Ming Liang ◽  
Qingzhao Wu ◽  
Shan Zhu ◽  
Naiqin Zhao ◽  
...  
Keyword(s):  
Structural Characteristics ◽  
Low Cost ◽  
Potassium Ion ◽  
Research Progress ◽  
Research Directions ◽  
Weak Charge ◽  
Recent Developments ◽  
High Theoretical Capacity ◽  
Further Development ◽  
Sodium And Potassium

AbstractThe development of sodium-ion (SIBs) and potassium-ion batteries (PIBs) has increased rapidly because of the abundant resources and cost-effectiveness of Na and K. Antimony (Sb) plays an important role in SIBs and PIBs because of its high theoretical capacity, proper working voltage, and low cost. However, Sb-based anodes have the drawbacks of large volume changes and weak charge transfer during the charge and discharge processes, thus leading to poor cycling and rapid capacity decay. To address such drawbacks, many strategies and a variety of Sb-based materials have been developed in recent years. This review systematically introduces the recent research progress of a variety of Sb-based anodes for SIBs and PIBs from the perspective of composition selection, preparation technologies, structural characteristics, and energy storage behaviors. Moreover, corresponding examples are presented to illustrate the advantages or disadvantages of these anodes. Finally, we summarize the challenges of the development of Sb-based materials for Na/K-ion batteries and propose potential research directions for their further development.

scholarly journals Risks and risk management in modern multiple sclerosis immunotherapeutic treatment

2019 ◽  
Vol 12 ◽  
pp. 175628641983657 ◽  
Author(s):  
Luisa Klotz ◽  
Joachim Havla ◽  
Nicholas Schwab ◽  
Reinhard Hohlfeld ◽  
Michael Barnett ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effect ◽  
Paradigm Shift ◽  
Mechanisms Of Action ◽  
Optimal Choice ◽  
New Drugs ◽  
Comprehensive Overview ◽  
Disease Modifying Drugs ◽  
Practical Recommendations ◽  
Target Effects

In recent years, there has been a paradigm shift in the treatment of multiple sclerosis (MS) owing to the approval of a number of new drugs with very distinct mechanisms of action. All approved disease-modifying drugs primarily work directly on the immune system. However, the identification of an ‘optimal choice’ for individual patients with regard to treatment efficacy, treatment adherence and side-effect profile has become increasingly complex including conceptual as well as practical considerations. Similarly, there are peculiarities and specific requirements with regard to treatment monitoring, especially in relation to immunosuppression, the development of secondary immune-related complications, as well as the existence of drug-specific on- and off-target effects. Both classical immunosuppression and selective immune interventions generate a spectrum of potential therapy-related complications. This article provides a comprehensive overview of available immunotherapeutics for MS and their risks, detailing individual mechanisms of action and side-effect profiles. Furthermore, practical recommendations for patients treated with modern MS immunotherapeutics are provided.

scholarly journals Research progress of carbon-assisted etching of silicon nanostructures

2021 ◽  
Vol 2076 (1) ◽  
pp. 012060
Author(s):  
Xiaoyu Yang ◽  
Ling Tong ◽  
Lin Wu ◽  
Baoguo Zhang ◽  
Zhiyuan Liao ◽  
...  
Keyword(s):  
Large Scale ◽  
Low Cost ◽  
Lithium Ion ◽  
Development Trend ◽  
Research Progress ◽  
Silicon Nanostructures ◽  
Storage Devices ◽  
Existing Problems ◽  
Energy Conversion And Storage ◽  
Silicon Based

Abstract Silicon nanostructures are attracting growing attention due to their properties and promising application prospects in solar energy conversion and storage devices, thermoelectric devices, lithium-ion batteries, and biosensing technologies. The large-scale and low-cost preparation of silicon nanostructures is critical for silicon-based advanced functional devices commercialization. In this paper, the feasibility and mechanism of silicon nanostructure fabricated by non-metallic carbon catalytic etching, as well as the currently existing problems and future development trend are reviewed.

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