Insight into 2019 novel coronavirus - An updated interim review and lessons from SARS-CoV and MERS-CoV.
ABSTRACT: BACKGROUND:The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions. METHODS:Based on recently published literature, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. RESULTS:The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicated a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immunization (when possible). CONCLUSION:The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.
Project description:Viral respiratory diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) always pose a severe threat to people. First identified in late December 2019, a novel coronavirus (2019-nCoV; SARS-CoV-2) has affected many provinces in China and multiple countries worldwide. The viral outbreak has aroused panic and a public-health emergency around the world, and the number of infections continues to rise. However, the causes and consequences of the pneumonia remain unknown. To effectively implement epidemic prevention, early identification and diagnosis are critical to disease control. Here we scrutinise a series of available studies by global scientists on the clinical manifestations, detection methods and treatment options for the disease caused by SARS-CoV-2, named coronavirus disease 2019 (COVID-19), and also propose potential strategies for preventing the infection.
Project description:The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.
Project description:Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths.1 COVID-19 causes a severe pneumonia characterized by fever, cough and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extrapulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multiorgan manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What is more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.
Project description:Immune dysfunction and aberrant cytokine storms often lead to rapid exacerbation of the disease during late infection stages in SARS-CoV and MERS-CoV patients. However, the underlying immunopathology mechanisms are not fully understood, and there has been little progress in research regarding the development of vaccines, anti-viral drugs, and immunotherapy. The newly discovered SARS-CoV-2 (2019-nCoV) is responsible for the third coronavirus pandemic in the human population, and this virus exhibits enhanced pathogenicity and transmissibility. SARS-CoV-2 is highly genetically homologous to SARS-CoV, and infection may result in a similar clinical disease (COVID-19). In this review, we provide detailed knowledge of the pathogenesis and immunological characteristics of SARS and MERS, and we present recent findings regarding the clinical features and potential immunopathogenesis of COVID-19. Host immunological characteristics of these three infections are summarised and compared. We aim to provide insights and scientific evidence regarding the pathogenesis of COVID-19 and therapeutic strategies targeting this disease.
Project description:Over the past two decades, there have been two major outbreaks where the crossover of animal Betacoronaviruses to humans has resulted in severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In December 2019, a global public health concern started with the emergence of a new strain of coronavirus (SARS-CoV-2 or 2019 novel coronavirus, 2019-nCoV) which has rapidly spread all over the world from its origin in Wuhan, China. SARS-CoV-2 belongs to the Betacoronavirus genus, which includes human SARS-CoV, MERS and two other human coronaviruses (HCoVs), HCoV-OC43 and HCoV-HKU1. The fatality rate of SARS-CoV-2 is lower than the two previous coronavirus epidemics, but it is faster spreading and the large number of infected people with severe viral pneumonia and respiratory illness, showed SARS-CoV-2 to be highly contagious. Based on the current published evidence, herein we summarize the origin, genetics, epidemiology, clinical manifestations, preventions, diagnosis and up to date treatments of SARS-CoV-2 infections in comparison with those caused by SARS-CoV and MERS-CoV. Moreover, the possible impact of weather conditions on the transmission of SARS-CoV-2 is also discussed. Therefore, the aim of the present review is to reconsider the two previous pandemics and provide a reference for future studies as well as therapeutic approaches.
Project description:Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic coronavirus named SARS-CoV-2 (previously known as 2019-nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS-CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical symptoms similar to those reported for SARS-CoV and MERS-CoV. The most characteristic symptom of patients with COVID-19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID-19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS-CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse-connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS-CoV and SARS-CoV2, it remains to make clear whether the potential invasion of SARS-CoV2 is partially responsible for the acute respiratory failure of patients with COVID-19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS-CoV-2-induced respiratory failure.
Project description:Recently, a novel coronavirus initially designated 2019-nCoV but now termed SARS-CoV-2 has emerged and raised global concerns due to its virulence. SARS-CoV-2 is the etiological agent of "coronavirus disease 2019", abbreviated to COVID-19, which despite only being identified at the very end of 2019, has now been classified as a pandemic by the World Health Organization (WHO). At this time, no specific prophylactic or postexposure therapy for COVID-19 are currently available. Viral entry is the first step in the SARS-CoV-2 lifecycle and is mediated by the trimeric spike protein. Being the first stage in infection, entry of SARS-CoV-2 into host cells is an extremely attractive therapeutic intervention point. Within this review, we highlight therapeutic intervention strategies for anti-SARS-CoV, MERS-CoV, and other coronaviruses and speculate upon future directions for SARS-CoV-2 entry inhibitor designs.
Project description:The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV), took tens of thousands of lives and caused tremendous economic losses. The main protease (Mpro) of SARS-CoV-2 is a potential target for treatment of COVID-19 due to its critical role in maturation of viral proteins and subsequent viral replication. Conceptually and technically, targeting therapy against Mpro is similar to target therapy to treat cancer. Previous studies show that GC376, a broad-spectrum dipeptidyl Mpro inhibitor, efficiently blocks the proliferation of many animal and human coronaviruses including SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), porcine epidemic diarrhea virus (PEDV), and feline infectious peritonitis virus (FIPV). Due to the conservation of structure and catalytic mechanism of coronavirus main protease, repurposition of GC376 against SARS-CoV-2 may be an effective way for the treatment of COVID-19 in humans. To validate this conjecture, the binding affinity and IC50 value of Mpro with GC376 was determined by isothermal titration calorimetry (ITC) and fluorescence resonance energy transfer (FRET) assay, respectively. The results showed that GC376 binds to SARS-CoV-2 Mpro tightly (KD = 1.6 ?M) and efficiently inhibit its proteolytic activity (IC50 = 0.89 ?M). We also elucidate the high-resolution structure of dimeric SARS-CoV-2 Mpro in complex with GC376. The cocrystal structure showed that GC376 and the catalytic Cys145 of Mpro covalently linked through forming a hemithioacetal group and releasing a sulfonic acid group. Because GC376 is already known as a broad-spectrum antiviral medication and successfully used in animal, it will be a suitable candidate for anti-COVID-19 treatment.
Project description:Coronavirus disease 2019 (COVID-19) is a viral pneumonia, responsible for the recent pandemic, and originated from Wuhan, China, in December 2019. The causative agent of the outbreak was identified as coronavirus and designated as severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Few years back, the severe acute respiratory syndrome coronavirus (SARS- CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) were reported to be highly pathogenic and caused severe infections in humans. In the current situation SARS-CoV-2 has become the third highly pathogenic coronavirus that is responsible for the present outbreak in human population. At the time of this review, there were more than 14 007 791 confirmed COVID-19 patients which associated with over 597 105 deaths in more then 216 countries across the globe (as reported by World Health Organization). In this review we have discussed about SARS-CoV, MERS-CoV and SARC-CoV-2, their reservoirs, role of spike proteins and immunogenicity. We have also covered the diagnosis, therapeutics and vaccine status of SARS-CoV-2.
Project description:Cold viruses have generally been considered fairly innocuous until the appearance of the severe acute respiratory coronavirus 2 (SARS-CoV-2) in 2019, which caused the coronavirus disease 2019 (COVID-19) global pandemic. Two previous viruses foreshadowed that a coronavirus could potentially have devastating consequences in 2002 [severe acute respiratory coronavirus (SARS-CoV)] and in 2012 [Middle East respiratory syndrome coronavirus (MERS-CoV)]. The question that arises is why these viruses are so different from the relatively harmless cold viruses. On the basis of an analysis of the current literature and using bioinformatic approaches, we examined the potential human miRNA interactions with the SARS-CoV-2's genome and compared the miRNA target sites in seven coronavirus genomes that include SARS-CoV-2, MERS-CoV, SARS-CoV, and four nonpathogenic coronaviruses. Here, we discuss the possibility that pathogenic human coronaviruses, including SARS-CoV-2, could modulate host miRNA levels by acting as miRNA sponges to facilitate viral replication and/or to avoid immune responses.