Human Severe Acute Respiratory Syndrome Research Articles

Identification of Hub genes associated with infection of three lung cell lines by SARS-CoV-2 with integrated bioinformatics analysis.

Identification of Hub genes associated with infection of three lung cell lines by SARS-CoV-2 with integrated bioinformatics analysis.

Hypothesis: The potential therapeutic role of nicorandil in COVID-19.

At present, there is yet no specific antiviral treatment or immunization against the newly identified human severe acute respiratory syndrome virus (SARS‐CoV2) that results in a rapidly progressive pandemic coronavirus disease 2019 (COVID‐19). We believe in a crucial need for a clinical strategy to counteract this viral pandemic based on the known pathogenesis throughout the disease course. Evidence suggests that exaggerated patient's inflammatory response and oxidative stress are likely to aggravate the disease pathology. The resulting endothelial dysfunction further induces fibrosis and coagulopathy. These disturbances can generate severe acute respiratory distress syndrome (ARDS) that can progress into respiratory and circulatory failure. Nicorandil is an anti‐anginal vasodilator drug acts by increasing nitric oxide bioavailability and opening of the KATP channel. Recently, nicorandil has been recognized to possess multiple protective effects against tissue injury. Here, we address a possible modulatory role of nicorandil against COVID‐19 pathogenesis. We hypothesise nicorandil would be an effective form of adjuvant therapy against COVID‐19.

A Proposed Weapon in the Anti-COVID-19 Arsenal: Percutaneous Zinc Absorption

Coronaviruses are large, enveloped, single-stranded, positive-sense RNA viruses with a genome of approximately 30 kilobases in length. The genus Coronavirus belongs to the family Coronaviridae in the order Nidovirales. They are classified into three groups. Group 1 contains various mammalian viruses including porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus, and human coronaviruses 229E and NL63. Group 2 includes canine respiratory coronavirus among other mammalian viruses and human coronavirus OC43. Human severe acute respiratory syndrome coronavirus (SARS-CoV) is considered a distant relative of this group. Group 3 contains solely avian coronaviruses. Human coronaviruses (HCoVs) cause respiratory infections, mainly, but gastroenteritis and neurological disorders may also occur. So far, at least six human coronaviruses have been described including SARS-CoV2, which was just identified in 2020, and two of these coronaviruses (OC43 and 229E) are responsible for 10-30% of all common colds. HCoV-HKU1 is mostly associated with bronchiolitis and pneumonia.

Mapping genome variation of SARS-CoV-2 worldwide highlights the impact of COVID-19 super-spreaders.

The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the twenty-first century. We analyzed more than 4700 SARS-CoV-2 genomes and associated metadata retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus genome. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and more than 160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a rather uniform mutation occurrence along branches that could have implications for diagnostics and the design of future vaccines. Identification of the root of SARS-CoV-2 genomes is not without problems, owing to conflicting interpretations derived from either using the bat coronavirus genomes as an outgroup or relying on the sampling chronology of the SARS-CoV-2 genomes and TMRCA estimates; however, the overall scenario favors haplogroup A as the ancestral node. Phylogenetic analysis indicates a TMRCA for SARS-CoV-2 genomes dating to November 12, 2019, thus matching epidemiological records. Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to subclade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe. Multiple founder effect episodes, most likely associated with super-spreader hosts, might explain COVID-19 pandemic to a large extent.

Highly sensitive and specific diagnosis of COVID-19 by reverse transcription multiple cross-displacement amplification-labelled nanoparticles biosensor.

BackgroundThe ongoing outbreak of the novel human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known as 2019-nCoV) has become a global health concern. Rapid and easy-to-use diagnostic techniques are urgently needed to diagnose SARS-CoV-2 infection.MethodsWe devised a reverse transcription multiple cross-displacement amplification (RT-MCDA) coupled with a nanoparticle-based biosensor assay (RT-MCDA-BS) for rapid, sensitive and specific diagnosis of coronavirus disease 2019 (COVID-19). Two primer sets were designed to target the open reading frame 1a/b and nucleoprotein gene of SARS-CoV-2. A total of 183 clinical samples, including 65 patients with COVID-19 infection and 118 patients with other pathogen infections were used to testify the assay's feasibility. Diagnosis results were reported visually using the biosensor.FindingsThe assay designed was performed using a simple instrument which could maintain the reaction in a constant temperature at 64°C for only 35 min. The total COVID-19 RT-MCDA-BS test procedure could be finished within 1 h. The COVID-19 RT-MCDA-BS could detect down to five copies of target sequences. Among 65 clinical samples from the COVID-19 patients, 22 (33.8%) positive results were obtained from faeces, nasal, pharyngeal and anal swabs via COVID-19 RT-MCDA-BS assay, while real-time reverse transcription-PCR assay only detected 20 (30.7%) positive results in these samples. No positive results were obtained from clinical samples with non-COVID-19 infections.InterpretationCOVID-19 RT-MCDA-BS was a rapid, reliable, low-cost and easy-to-use assay, which could provide an attractive laboratory tool to diagnose COVID-19 in multiple clinical specimens, especially for field, clinic laboratories and primary care facilities in resource-poor settings.

Lessons learned from early compassionate use of convalescent plasma on critically ill patients with Covid-19.

BackgroundThe management of critically ill patients with coronavirus disease 2019 (COVID‐19), caused by a new human virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is challenging. Recently, there have been several reports with inconsistent results after treatment with convalescent plasma (CP) on critically ill patients with COVID‐19, which was produced with a neutralizing antibody titer and tested in a P3 or P4 laboratory. However, due to the limitation of the conditions on mass production of plasma, most producers hardly had the capability to isolate the neutralizing antibody. Here, we report the clinical courses of three critically ill patients with COVID‐19 receiving CP treatments by total immunoglobulin G (IgG) titer collection.MethodsThree patients with COVID‐19 in this study were laboratory confirmed to be positive for SARS‐CoV‐2, with radiographic and clinical features of pneumonia. CP was collected by total IgG titer of 160 (range, 200‐225 mL), and patients were transfused between 20 and 30 days after disease onset at the critical illness stage as a trial in addition to standard care. The clinical courses of these patients, including laboratory results and pulmonary functional and image studies after receiving convalescent plasma infusions, were reviewed.ResultsNo therapeutic effect of CP was observed in any of the patients; instead, all three patients deteriorated and required extracorporeal membrane oxygenation treatment. A potential cytokine storm 4 hours after infusion of CP in Patient 2 was observed. No more patients were put on the trial of CP transfusion.ConclusionsWe recommend extreme caution in using CP in critically ill patients more than 2 weeks after the onset of COVID‐19 pneumonia.

Genetic variations in the human severe acute respiratory syndrome coronavirus receptor ACE2 and serine protease TMPRSS2

AimsThe recent emergence of novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health emergency. The coronaviral entry requires the spike (S)-protein for attachment to the host...

Immunomodulatory Effects of Hydroxychloroquine and Chloroquine in Viral Infections and Their Potential Application in Retinal Gene Therapy.

Effective treatment of retinal diseases with adeno-associated virus (AAV)-mediated gene therapy is highly dependent on the proportion of successfully transduced cells. However, due to inflammatory reactions at high vector doses, adjunctive treatment may be necessary to enhance the therapeutic outcome. Hydroxychloroquine and chloroquine are anti-malarial drugs that have been successfully used in the treatment of autoimmune diseases. Evidence suggests that at high concentrations, hydroxychloroquine and chloroquine can impact viral infection and replication by increasing endosomal and lysosomal pH. This effect has led to investigations into the potential benefits of these drugs in the treatment of viral infections, including human immunodeficiency virus and severe acute respiratory syndrome coronavirus-2. However, at lower concentrations, hydroxychloroquine and chloroquine appear to exert immunomodulatory effects by inhibiting nucleic acid sensors, including toll-like receptor 9 and cyclic GMP-AMP synthase. This dose-dependent effect on their mechanism of action supports observations of increased viral infections associated with lower drug doses. In this review, we explore the immunomodulatory activity of hydroxychloroquine and chloroquine, their impact on viral infections, and their potential to improve the efficacy and safety of retinal gene therapy by reducing AAV-induced immune responses. The safety and practicalities of delivering hydroxychloroquine into the retina will also be discussed.

The case for adopting a combined comparative medicine and One Health approach to tackle emerging diseases

The majority of emerging infectious diseases are zoonotic, originating from domesticated animals and wildlife.1 The Covid-19 pandemic is also a zoonosis, with current evidence suggesting that the causative agent –...

An Overview of the Genetic Variations of the SARS-CoV-2 Genomes Isolated in Southeast Asian Countries.

Monitoring the mutation dynamics of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in understanding its infectivity, virulence and pathogenicity for development of a vaccine. In an "age of mobility," the pandemic highlights the importance and vulnerability of regionalization and labor market interdependence in Southeast Asia. We intend to characterize the genetic variability of viral populations within the region to provide preliminary information for regional surveillance in the future. By analyzing 142 complete genomes from South East Asian (SEA) countries, we identified three central variants distinguished by nucleotide and amino acid changes.

Perspectives on the recommendations for skin cancer management during the COVID-19 pandemic

The National Comprehensive Cancer Network and American College of Mohs Surgery have released guidelines for managing cancer during the human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The detailed National Comprehensive Cancer Network and American College of Mohs Surgery recommendations are available online (https://www.nccn.org/covid-19/default.aspx and https://www.mohscollege.org/), and here we provide our perspective.1

Post-donation COVID-19 identification in blood donors.

The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].

In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel

Recent outbreak of Coronavirus disease (COVID-19) pandemic around the world is associated with ‘severe acute respiratory syndrome’ (SARS-CoV2) in humans. SARS-CoV2 is an enveloped virus and E proteins present in them are reported to form ion channels, which is mainly associated with pathogenesis. Thus, there is always a quest to inhibit these ion channels, which in turn may help in controlling diseases caused by SARS-CoV2 in humans. Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human ‘SARS-CoV2 E’ protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. However, after binding with Belachinal, Macaflavanone E, and Vibsanol B, the random motion of the human ‘SARS-CoV2 E’ protein gets reduced, this, in turn, inhibits the function of the ‘SARS-CoV2 E’ protein. It is pertinent to note that two amino acids, namely VAL25 and PHE26, play a key role while interacting with these three phytochemicals. As these three phytochemicals, namely, Belachinal, Macaflavanone E & Vibsanol B, have passed the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) property as well as ‘Lipinski’s Rule of 5s’, they may be utilized as drugs in controlling disease caused via SARS-COV2, after further investigation. Communicated by Ramaswamy H. Sarma

Back to the basics: Diluted bleach for COVID-19

To the Editor: Since December 2019, COVID-19. a highly pathogenic novel human coronavirus severe acute respiratory syndrome coronavirus (SARS-Cov-2), has emerged from China harboring high human-to-human transmission rates and persistence on inanimate surfaces.1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar An analysis of 22 studies revealed that human coronaviruses similar to COVID-19, including SARS coronavirus, Middle East respiratory syndrome (MERS) coronavirus, and endemic human coronaviruses (HCoV), can persist on inanimate surfaces, such as metal, glass, or plastic, for up to 9 days, but are efficiently inactivated by 62% to 71% ethanol, 0.5% hydrogen peroxide, or 0.1% sodium hypochlorite within 1 minute.1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar A study by van Doremalen et al2van Doremalen N. Bushmaker T. Morris D.H. et al.Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1.N Engl J Med. 2020; Crossref Scopus (5624) Google Scholar evaluating the stability of COVID-19 and SARS-CoV-1 suggests that COVID-19 may remain viable for hours to days on surfaces made from a variety of materials. To help identify commercial disinfectants against COVID-19, the United States Environmental Protection Agency (EPA) has created a list of adequate products by their EPA registration number.3United States Environmental Protection AgencyPesticide Registration. List N: disinfectants for Use Against SARS-CoV-2.https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2Date: 2020Date accessed: March 20, 2020Google Scholar Unfortunately, with exponentially rising COVID-19 cases in the United States, commercial disinfect supplies are in high demand and will unquestionably be limited in the near future. We will have to get creative with available resources, all the while taking safe precautions to ensure our efforts improve and not worsen the ongoing situation. Various dilutions of sodium hypochlorite, effectively Dakin's solution, have been tried and true in dermatology and wound care for many years. To achieve the formulation noted by Kampf et al,1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar ∼0.1% sodium hypochlorite can be made by a roughly 1:50 dilution of household bleach (∼5.25% to 6% sodium hypochlorite) in tap water. Although the Kampf et al analysis is a combination of non–COVID-19 studies, we expect the proposed formulation to similarly also disinfect surfaces of the novel coronavirus. The Centers for Disease Control and Prevention (CDC) also recommends an approximately 1:50 dilution to disinfect COVID-19, explicitly noting 5 tablespoons (one-third cup) bleach per gallon of water or 4 teaspoons bleach per quart of water.4Centers for Disease Control and PreventionClean & Disinfect-Coronavirus Disease 2019: interim Recommendations for U.S. Households with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19).https://www.cdc.gov/coronavirus/2019-ncov/prepare/cleaning-disinfection.htmlDate accessed: March 20, 2020Google Scholar Different dilutions of sodium hypochlorite can vary in their in vivo fibroblast and keratinocyte cytotoxicity; however, dilutions of ∼0.1% sodium hypochlorite are clinically effective with minimal irritation or sensitization.5Ronco C. Mishkin G.J. Disinfection by Sodium Hypochlorite: Dialysis Applications. Karger, Basel, Switzerland2007Google Scholar One should be mindful that corrosive injury on mucous membrane/skin contact is possible with excess volumes or mishandling, so appropriate caution and moderation is necessary.6Slaughter R.J. Watts M. Vale J.A. Grieve J.R. Schep L.J. The clinical toxicology of sodium hypochlorite.Clin Toxicol (Phila). 2019; 57: 303-311Crossref PubMed Scopus (66) Google Scholar This solution should ideally be used within 1 month of preparation and stored in a closed, opaque container at room temperature.7National Research Council (US) and Institute of Medicine (US)Panel on Needle Exchange and Bleach Distribution Programs.in: Normand J. Vlahov D. Moses L.E. Preventing HIV Transmission: The Role of Sterile Needles and Bleach. National Academies Press (US), Washington, DC1995Google Scholar While the exact viral load on inanimate surfaces is unknown during an outbreak, it is critical to disinfect frequently touched surfaces.1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar With rapidly diminishing availability of commercial cleaning supplies, simple diluted bleach, which is readily available, can effectively disinfect our clinics, homes, and environment to prevent sustained transmission from inanimate objects. As with many disinfectants, minimizing long-term skin contact and ensuring good ventilation can minimize clinical toxicity. In Henry Dakin's spirit, we should strive to share with our colleagues the cost-effective, accessible, and relatively safe power of diluted bleach.

Phylogenetic network analysis of SARS-CoV-2 genomes

In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.

Clusters of Human Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in a Non-Epidemic Area, China

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is an emerging virus causing substantial morbidity and mortality worldwide We perf

Effects of Gene-Eden-VIR and Novirin on SARS-CoV: Implications for COVID-19.

The coronavirus (SARS-CoV-2), which causes COVID-19, is a betacoronavirus closely related to the human severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV). The recent COVID-19 outbreak created an urgent need for treatment. To expedite the development of such treatment, pharmaceutical companies and government agencies are currently testing several existing drugs for their effect on the virus. Gene-Eden-VIR and Novirin are natural, broad-spectrum, antiviral treatments proven to be safe and effective in several clinical studies. In this article, we present evidence indicating that the 5 Gene-Eden-VIR/Novirin ingredients have anti-betacoronavirus, and specifically, anti-SARS-CoV effects. We consider this evidence as a first indication of the anti-coronavirus effects of Gene-Eden-VIR/Novirin. Next, we are planning to conduct a clinical study with users of the treatments to test the effects of Gene-Eden-VIR/Novirin on individuals at risk and those infected with the virus.

Cardiopulmonary resuscitation in coronavirus disease 2019 patients

We are faced with a novel human severe acute respiratory syndrome coronavirus-2 (CoV-2) that has been pronounced a pandemic by the World Health Organization in March 2020. This virus is highly contagious and can result in a disease that has been named CoV disease 2019 (COVID-19). It is characterized by severe pneumonia followed by a cytokine storm that can result in death. In such situations, performing cardiopulmonary resuscitation (CPR) can be a huge challenge because the virus can infect healthcare workers (HCW). For this reason, The American Heart Association and The Resuscitation Council (UK) have modified their guidance on performing CPR in COVID-19 patients to give them the best chance of survival while protecting the HCW. In this review, we aim to summarize the literature and share our experience in resuscitating COVID-19 patients or persons under investigations.

Recent insights into clinical COVID-19 causing novel human coronavirus

As everyone on earth came is panic about recent pandemic about coronavirus disease 19 (COVID-19) which is the most transmissible, contagious, deadliest and pathogenic viral infection that is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China (Wuhan city). The genomic sequence alignment analysis confirmed the phylogenetic origin of SARSCoV-2 from severe acute respiratory syndrome-like (SARS-like). This outbreak is suspiciously originated as zoonotic from the bats which might be act as primary reservoir. But, the major source of origin reason for conversion of this virus as transmitting agent from zoonotic condition to human to humans is still unclear. However, this kind of human to human rapid transmission, the clear pathogenesis, ambiguity with its clinical manifestation, non availability of rapid diagnostic tools, and either lacking of clinically approved proper anti-COVID-19 drugs or non existence of preventive vaccine for SARS-CoV-1 is available till date. Hence, in this review, we are summarizing the basic nature of pathogenic COVID-19 virus, its source of origin, pathogenicity, life cycle, infection, immunological invade in the host, diagnosis, clinical manifestations, possible therapeutic approaches and preventive measures of novel human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) in comparison with middle east respiratory syndrome coronavirus (MERS-CoV).

A conserved region of nonstructural protein 1 from alphacoronaviruses inhibits host gene expression and is critical for viral virulence

Coronaviruses are enveloped, single-stranded RNA viruses that are distributed worldwide. They include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and the human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), many of which seriously endanger human health and well-being. Only alphacoronaviruses and betacoronaviruses harbor nonstructural protein 1 (nsp1), which performs multiple functions in inhibiting antiviral host responses. The role of the C terminus of betacoronavirus nsp1 in virulence has been characterized, but the location of the alphacoronavirus nsp1 region that is important for virulence remains unclear. Here, using TGEV nsp1 as a model to explore the function of this protein in alphacoronaviruses, we demonstrate that alphacoronavirus nsp1 inhibits host gene expression. Solving the crystal structure of full-length TGEV at 1.85-Å resolution and conducting several biochemical analyses, we observed that a specific motif (amino acids 91–95) of alphacoronavirus nsp1 is a conserved region that inhibits host protein synthesis. Using a reverse-genetics system based on CRISPR/Cas9 technology to construct a recombinant TGEV in which this specific nsp1 motif was altered, we found that this mutation does not affect virus replication in cell culture but significantly reduces TGEV pathogenicity in pigs. Taken together, our findings suggest that alphacoronavirus nsp1 is an essential virulence determinant, providing a potential paradigm for the development of a new attenuated vaccine based on modified nsp1.