scholarly journals Current Perspectives in the Discovery of Newer Medications Against the Outbreak of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
M. Ramesh ◽  
Krishnan Anand ◽  
Mohd Shahbaaz ◽  
Magda H. Abdellattif
Keyword(s):  
Small Molecules ◽  
Viral Entry ◽  
Respiratory Illness ◽  
Disease Outbreak ◽  
Spike Protein ◽  
Severe Illness ◽  
Human Lungs ◽  
Synthetic Approaches ◽  
Severe Respiratory Illness

A rapid and increasing spread of COVID-19 pandemic disease has been perceived worldwide in 2020. The current COVID-19 disease outbreak is due to the spread of SARS-CoV-2. SARS-CoV-2 is a new strain of coronavirus that has spike protein on the envelope. The spike protein of the virus binds with the ACE-2 receptor of the human lungs surface for entering into the host. Therefore, the blocking of viral entry into the host by targeting the spike protein has been suggested to be a valid strategy to treat COVID-19. The patients of COVID-19 were found to be asymptomatic, cold, mild to severe respiratory illness, and leading to death. The severe illness has been noted mainly in old age people, cardiovascular disease patients, and respiratory disease patients. However, the long-term health effects due to COVID-19 are not yet known. Recently, the vaccines were authorized to protect from COVID-19. However, the researchers have put an effort to discover suitable targets and newer medications in the form of small molecules or peptides, based on in-silico methods and synthetic approaches. This manuscript describes the current perspectives of the causative agent, diagnostic procedure, therapeutic targets, treatment, clinical trials, and development of potential clinical candidates of COVID-19. The study will be useful to identify the potential newer medications for the treatment of COVID-19.

scholarly journals Severe Respiratory Illness Outbreak Associated with Human Coronavirus NL63 in a Long-Term Care Facility

2018 ◽  
Vol 24 (10) ◽  
pp. 1964-1966 ◽  
Author(s):  
Julie Hand ◽  
Erica Billig Rose ◽  
Andrea Salinas ◽  
Xiaoyan Lu ◽  
Senthilkumar K. Sakthivel ◽  
...  
Keyword(s):  
Long Term Care ◽  
Care Facility ◽  
Respiratory Illness ◽  
Human Coronavirus ◽  
Term Care ◽  
Term Care Facility ◽  
Long Term Care Facility ◽  
Severe Respiratory Illness

scholarly journals Direct ACE2- Spike RBD Binding Disruption with Small Molecules: A Strategy for COVID-19 Treatment

2020 ◽  
Author(s):  
Sandra Smieszek ◽  
Bart Przychodzen ◽  
Vasilios Polymeropoulos ◽  
Christos Polymeropoulos ◽  
Mihael Polymeropoulos
Keyword(s):  
Small Molecules ◽  
Viral Entry ◽  
In Silico ◽  
Spike Protein ◽  
Interface Residue ◽  
Chemical Library ◽  
Susceptibility Data ◽  
Multiple Routes ◽  
Viral Nature

ACE2 is a key receptor for SARS-CoV-2 cell entry. Binding of SARS-Cov-2 to ACE2 involves the viral Spike protein. The molecular interaction between ACE2 and Spike has been resolved. Interfering with this interaction might be used in treating patients with COVID-19. Inhibition of this interaction can be attained via multiple routes: here we focus on identifying small molecules that would prevent the interaction. Specifically we focus on small molecules and peptides that have the capacity to effectively bind the ACE2: RBD contact domain to prevent and reduce SARS-CoV-2 entry into the cell. We aim to identify molecules that prevent the docking of viral spike protein (mediated by RBD) onto cells expressing ACE2, without inhibiting the activity of ACE2. We utilize the most recent ACE2-RBD crystallography resolved model (PDB-ID:6LZG). Based on animal susceptibility data we narrowed down our interest to the location of amino acid 34 (Histidine) located on ACE2. We performed an in silico screen of a chemical library of compounds with several thousand small molecules including FDA approved compounds. All compounds were tested for binding to the proximal binding site located close to histidine 34 on ACE2. We report a list of four potential small molecules that potentially have the capacity to bind target residue: AY-NH2, a selective PAR4 receptor agonist peptide (CAS number: 352017-71-1), NAD+ (CAS number: 53-84-9), Reproterol, a short-acting β2 adrenoreceptor agonist used in the treatment of asthma (CAS number: 54063-54-6), and Thymopentin, a synthetic immune-stimulant which enhances production of thymic T cells (CAS number: 69558-55-0). The focus is on a High Throughput Screen Assay (HTSA), or in silico screen, delineating small molecules that are selectively binding/masking the crucial interface residue on ACE2 at His34. Consequently, inhibiting SARS-CoV-2 binding to host ACE2 and viral entry is a potent strategy to reduce cellular entry of the virus. We suggest that this anti-viral nature of this interaction is a viable strategy for COVID19 whereas the small molecules including peptides warrant further in vitro screens.

scholarly journals SARS-CoV-2 Spike Protein and Lung Vascular Cells

2020 ◽  
Vol 1 (1) ◽  
pp. 40-48
Author(s):  
Sri Jayalakshmi Suresh ◽  
Yuichiro Justin Suzuki
Keyword(s):  
Membrane Fusion ◽  
Viral Entry ◽  
Biological Effects ◽  
Spike Protein ◽  
Vascular Cells ◽  
Membrane Fusion Protein ◽  
Vascular Walls ◽  
Immunodeficiency Virus ◽  
Pulmonary Arterial

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the current pandemic of coronavirus disease 2019 (COVID-19), and COVID-19 vaccines focus on its spike protein. However, in addition to facilitating the membrane fusion and viral entry, the SARS-CoV-2 spike protein promotes cell growth signaling in human lung vascular cells, and patients who have died of COVID-19 have thickened pulmonary vascular walls, linking the spike protein to a fatal disease, pulmonary arterial hypertension (PAH). In addition to SARS-CoV spike proteins, gp120, the viral membrane fusion protein of human immunodeficiency virus (HIV), has been reported to promote cell signaling, and long-term surviving HIV-positive patients have a high incidence of developing PAH. This article describes the findings of the SARS-CoV-2 spike protein affecting lung vascular cells and explains how the spike protein possibly increases the incidence of PAH. Since the SARS-CoV-2 spike protein will be administered to millions of people as COVID-19 vaccines, it is critical to understand the biological effects of this protein on human cells to ensure that it does not promote long-term adverse health consequences.

scholarly journals Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 705 ◽  
Author(s):  
Jennifer Santos ◽  
Stephanie Brierley ◽  
Mohit J. Gandhi ◽  
Michael A. Cohen ◽  
Phillip C. Moschella ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Viral Entry ◽  
Therapeutic Potential ◽  
Respiratory Illness ◽  
Therapeutic Options ◽  
The Novel ◽  
Potential Efficacy ◽  
Humanized Monoclonal Antibodies ◽  
Severe Respiratory Illness

The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.

SARS-CoV-2 S Protein Binding hACE2: Viral Entry, Pathogenesis, Prognosis, and Potential Therapeutic Targets

2020 ◽  
Author(s):  
Lobna Al-Zaidan ◽  
Sarra Mestiri ◽  
Afsheen Raza ◽  
Maysaloun Merhi ◽  
Varghese Inchakalody ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Viral Entry ◽  
Respiratory Illness ◽  
Host Cells ◽  
Host Susceptibility ◽  
Unknown Etiology ◽  
Viral Binding ◽  
Binding Interface ◽  
Novel Coronavirus ◽  
Severe Respiratory Illness

Pneumonia cases of unknown etiology in Wuhan, China, were reported to the WHO on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender and underlying comorbidities. Importantly, SARS-CoV and SARS-CoV-2 entry into the host cells is mediated via ACE2 receptor. However, ACE2 receptor binding affinity to SARS-CoV-2 is 4 folds higher than that to SARS-CoV. Identification of different aspects such as binding affinity, differential antigenic profiles of spike glycoproteins, and ACE2 polymorphisms might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. Here we aim to elaborate on SARS-CoV-2 S1/ACE2 ligand that facilitates viral internalization as well as to highlight the differences between SARS-CoVs binding affinity to ACE2. We also discuss the possible immunogenic sequences of spike glycoprotein and the effect of ACE2 polymorphism on viral binding/infectivity and host susceptibility to disease. Furthermore, targeting of ACE2 will be discussed to understand its role in therapeutics.

scholarly journals Direct ACE2- Spike RBD Binding Disruption with Small Molecules: A Strategy for COVID-19 Treatment

2020 ◽  
Author(s):  
Sandra Smieszek ◽  
Bart Przychodzen ◽  
Vasilios Polymeropoulos ◽  
Christos Polymeropoulos ◽  
Mihael Polymeropoulos
Keyword(s):  
Small Molecules ◽  
Viral Entry ◽  
In Silico ◽  
Spike Protein ◽  
Interface Residue ◽  
Chemical Library ◽  
Susceptibility Data ◽  
Multiple Routes ◽  
Viral Nature

ACE2 is a key receptor for SARS-CoV-2 cell entry. Binding of SARS-Cov-2 to ACE2 involves the viral Spike protein. The molecular interaction between ACE2 and Spike has been resolved. Interfering with this interaction might be used in treating patients with COVID-19. Inhibition of this interaction can be attained via multiple routes: here we focus on identifying small molecules that would prevent the interaction. Specifically we focus on small molecules and peptides that have the capacity to effectively bind the ACE2: RBD contact domain to prevent and reduce SARS-CoV-2 entry into the cell. We aim to identify molecules that prevent the docking of viral spike protein (mediated by RBD) onto cells expressing ACE2, without inhibiting the activity of ACE2. We utilize the most recent ACE2-RBD crystallography resolved model (PDB-ID:6LZG). Based on animal susceptibility data we narrowed down our interest to the location of amino acid 34 (Histidine) located on ACE2. We performed an in silico screen of a chemical library of compounds with several thousand small molecules including FDA approved compounds. All compounds were tested for binding to the proximal binding site located close to histidine 34 on ACE2. We report a list of four potential small molecules that potentially have the capacity to bind target residue: AY-NH2, a selective PAR4 receptor agonist peptide (CAS number: 352017-71-1), NAD+ (CAS number: 53-84-9), Reproterol, a short-acting β2 adrenoreceptor agonist used in the treatment of asthma (CAS number: 54063-54-6), and Thymopentin, a synthetic immune-stimulant which enhances production of thymic T cells (CAS number: 69558-55-0). The focus is on a High Throughput Screen Assay (HTSA), or in silico screen, delineating small molecules that are selectively binding/masking the crucial interface residue on ACE2 at His34. Consequently, inhibiting SARS-CoV-2 binding to host ACE2 and viral entry is a potent strategy to reduce cellular entry of the virus. We suggest that this anti-viral nature of this interaction is a viable strategy for COVID19 whereas the small molecules including peptides warrant further in vitro screens.

A Fused Thiophene-S,S-Dioxide-Based Super-Photostable Fluorescent Marker for Lipid Droplets

2020 ◽  
Author(s):  
Masayasu Taki ◽  
Keiji Kajiwara ◽  
Eriko Yamaguchi ◽  
Yoshikatsu Sato ◽  
Shigehiro Yamaguchi
Keyword(s):  
Small Molecules ◽  
Lipid Droplets ◽  
Trajectory Analysis ◽  
Super Resolution ◽  
Fluorescent Marker ◽  
Selective Staining ◽  
Fluorescent Markers ◽  
Biological Studies ◽  
Particle Level

Lipid droplets (LDs) are essential organelle in most eukaryotes, and tracking intracellular LDs dynamics using synthetic small molecules is crucial for biological studies. However, only a limited number of fluorescent markers that satisfy all requirements, such as the selective staining of LDs, high photostability, and sufficient biocompatibility, have been developed. Herein, we report a series of donor-p-acceptor dyes based on the thiophene-containing fused polycyclic scaffold [1]benzothieno[3,2-<i>b</i>][1]benzothiophene (BTBT), in which either or both thiophene rings are oxidized into thiophene-<i>S</i>,<i>S</i>-dioxide to form an electron-accepting building block. Among these dyes, LAQ1 satisfied all the aforementioned requirements, and allowed us capturing ultra-small LDs on the endoplasmic reticulum (ER) membrane by stimulation emission depletion (STED) microscopy with a super-resolution below the diffraction limit of light. Moreover, the extremely high photostability of LAQ1 enabled recording the lipolysis of LDs and the concomitant lipogenesis as well as long-term trajectory analysis of micro LDs at the single particle level in living cells.

A Potential Role of Coenzyme Q10 Deficiency in Severe SARS-CoV2 Infection

2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Vasilios M. Polymeropoulos ◽  
Keyword(s):  
Viral Entry ◽  
Coenzyme Q10 ◽  
Severe Infection ◽  
The Body ◽  
Therapeutic Options ◽  
Severe Illness ◽  
Infected People ◽  
Inflammatory State ◽  
Exogenous Compounds ◽  
Obesity Hypertension

There is a dramatic need for extensive research into the predictors of severe infection with SARS-CoV2 and therapeutic options for infected people. People who suffer from severe illness and higher mortality display a pattern of having specific co-morbidities (diabetes, obesity, hypertension) and are of higher age. Recent research has described methods of viral entry via receptors (ACE2, TMPRSS2) and the hyper-inflammatory state often associated with severe illness (increase in interleukins, increase in TNF-alpha). These discoveries have led to the research of currently available and developing therapies, that are helpful to patients. Deficiencies of specific vitamins and other endogenous molecules of the body should be examined to understand if a pattern exists among the people most severely affected. Coenzyme Q10 (CoQ10) is a fat-soluble substance ubiquitously expressed throughout the body that is important for the generation of ATP and mediation of inflammatory disease. CoQ10 faces a decline with increasing age, genetic predispositions, and ingestion of exogenous compounds that could reduce the level of CoQ10. Deficiencies and subsequent supplementation with CoQ10 recently has displayed encouraging results for the improvement of a wide variety of diseases. This manuscript is significant as it points to a potential relationship of CoQ10 and the population suffering from severe illness of COVID-19, and further encourages the need for research into measuring the levels of CoQ10 and vitamins to understand if levels predict severe illness and mortality. This could offer new avenues into research in combating this pandemic and potentially future therapeutic options.

scholarly journals To Swab or Not to Swab? The Lesson Learned in Italy in the Early Stage of the COVID-19 Pandemic

2021 ◽  
Vol 11 (9) ◽  
pp. 4042
Author(s):  
Paola Berchialla ◽  
Maria Teresa Giraudo ◽  
Carmen Fava ◽  
Andrea Ricotti ◽  
Giuseppe Saglio ◽  
...  
Keyword(s):  
Early Phase ◽  
Early Stage ◽  
Respiratory Illness ◽  
Explanatory Variables ◽  
Daily Number ◽  
Testing Strategies ◽  
Serious Infections ◽  
The Impact ◽  
Epidemiological Link ◽  
Severe Respiratory Illness

Testing for the SARS-CoV-2 infection is critical for tracking the spread of the virus and controlling the transmission dynamics. In the early phase of the pandemic in Italy, the decentralized healthcare system allowed regions to adopt different testing strategies. The objective of this paper is to assess the impact of the extensive testing of symptomatic individuals and their contacts on the number of hospitalizations against a more stringent testing strategy limited to suspected cases with severe respiratory illness and an epidemiological link to a COVID-19 case. A Poisson regression modelling approach was adopted. In the first model developed, the cumulative daily number of positive cases and a temporal trend were considered as explanatory variables. In the second, the cumulative daily number of swabs was further added. The explanatory variable, given by the number of swabs over time, explained most of the observed differences in the number of hospitalizations between the two strategies. The percentage of the expected error dropped from 70% of the first, simpler model to 15%. Increasing testing to detect and isolate infected individuals in the early phase of an outbreak improves the capability to reduce the spread of serious infections, lessening the burden of hospitals.

Sign in / Sign up

Export Citation Format

Share Document