Platforms for Personalized Polytherapeutics Discovery in COVID-19

The COVID-19 pandemic entered its third and most intense to date wave of infections in November 2020. This perspective article describes how combination therapies (polytherapeutics) are a needed focus for helping battle the severity of complications from SARS-CoV-2 infection. It outlines the types of systems that are needed for fast and efficient combinatorial assessment of therapeutic candidates. Proposed are micro-physiological systems using human iPSC as a format for tissue-specific modeling of infection, the use of gene-humanized zebrafish and C. elegans for combinatorial drug screens due to the animals being addressable in liquid multi-well formats, and the use of engineered pseudo-typing systems to safely model infection in the transgenic animals and engineered tissue systems.     

Exploring human-animal host interactions and emergence of COVID-19: Evolutionary and ecological dynamics

The novel coronavirus disease (COVID-19) that emerged in December 2019 had caused substantial morbidity and mortality at the global level within few months. It affected economies, stopped travel, and isolated individuals and populations around the world. Wildlife, especially bats, serve as reservoirs of coronaviruses from which the variant Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emerged that causes COVID-19. In this review, we describe the current knowledge on COVID-19 and the significance of wildlife hosts in its emergence. Mammalian and avian coronaviruses have diverse host ranges with distinct lineages of coronaviruses. Recombination and reassortments occur more frequently in mixed-animal markets where diverse viral genotypes intermingle. Human coronaviruses have evolved through gene gains and losses primarily in interfaces where wildlife and humans come in frequent contact. There is a gap in our understanding of bats as reservoirs of coronaviruses and there is a misconception that bats periodically transmit coronaviruses to humans. Future research should investigate bat viral diversity and loads at interfaces between humans and bats. Furthermore, there is an urgent need to evaluate viral strains circulating in mixed animal markets, where the coronaviruses circulated before becoming adapted to humans. We propose and discuss a management intervention plan for COVID-19 and raise questions on the suitability of current containment plans. We anticipate that more virulent coronaviruses could emerge unless proper measures are taken to limit interactions between diverse wildlife and humans in wild animal markets.     

An Infectious cDNA Clone of SARS-CoV-2

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2019新型冠状病毒及其诊疗与防控:回顾与展望

2019新型冠状病毒的暴发持续至今,导致了世界各地数以百万计的感染个例,更夺去了数十万人的生命。世界卫生组织在2020年2月将此病毒引起的疾病定名为2019冠状病毒病(Coronavirus disease 2019,COVID-19),而国际病毒分类委员会也将此病毒命名为SARS-Co V-2。COVID-19的典型临床症状类似感冒,少数病人可发展为重症甚至死亡。21世纪以来,人类冠状病毒有3次大暴发,分别是2003年暴发的严重急性呼吸综合征(SARS)、2012年暴发的中东呼吸综合征(MERS)和本次的新型肺炎。自2003年以来,对SARS和MERS冠状病毒的研究从未间断,对其自然起源、致病机理、药物筛选及疫苗研发等已取得一定进展。鉴于SARS-Co V-2和SARS-Co V的基因组序列高度相似,以往对SARS-Co V的研究对深入探讨SARS-Co V-2生物学特性、诊断、治疗和防控有很强的借鉴性。文中通过回顾过往的研究进展,对比SARS-Co V和SARS-Co V-2的生物学特性,分析当前亟需的防控和诊疗措施,探讨疫苗研发所面对的一些难题,并展望疫情发展趋势及对本领域研究与开发的主要挑战,冀为我国和全世界有效控制COVID-19疫情提供参考。     

The global impact of the coronavirus pandemic

The coronavirus pandemic has engulfed the nations of the world for the first five months of 2020 and altered the pace, fabric and nature of our lives. In this overview accompanying the Special Issue of Cytokine & Growth Factor Reviews, we examine some of the many social and scientific issues impacted by SARS-CoV2 – personal lives, economy, scientific communication, the environment. International members of Istituto Pasteur in Rome and INITIATE, the Marie Curie Training Network reflect on the lasting global impact of the coronavirus pandemic.     

A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV,and MERS-CoV

The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERSCoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.     

Genome composition and genetic characterization of SARS-CoV-2

SARS-CoV-2 is a type of Betacoronaviruses responsible for COVID-19 pandemic disease, with more than 1.745 million fatalities globally as of December-2020. Genetically, it is considered the second largest genome of all RNA viruses with a 5′ cap and 3′ poly-A tail. Phylogenetic analyses of coronaviruses reveal that SARS-CoV-2 is genetically closely related to the Bat-SARS Like-Corona virus (Bat-SL-Cov) with 96% whole-genome identity. SARS-CoV-2 genome consists of 15 ORFs coded into 29 proteins. At the 5′ terminal of the genome, we have ORF1ab and ORF1a, which encode the 1ab and 1a polypeptides that are proteolytically cleaved into 16 different nonstructural proteins (NSPs). The 3′ terminal of the genome represents four structural (spike, envelope, matrix, and nucleocapsid) and nine accessory (3a, 3b, 6, 7a, 7b, 8b, 9a, 9b, and orf10) proteins. As the number of COVID-19 patients increases dramatically worldwide, there is an urgent need to find a quick and sensitive diagnostic tool for controlling the outbreak of SARS-CoV-2 in the community. Today, molecular testing methods utilizing viral genetic material (e.g., PCR) represent the crucial diagnostic tool for the SARS-CoV-2 virus despite its low sensitivity in the early stage of viral infection. This review summarizes the genome composition and genetic characterization of the SARS-CoV-2.     

A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.     

Recent Clinical Trials on Natural Products and Traditional Chinese Medicine Combating the COVID-19

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing potentially fatal coronavirus disease-19 (COVID-19), with a significant health and economic burden around the globe. Currently many clinical studies are undergoing but still there is no any specific approved therapy or drug established for effective treatment of COVID-19. This review aimed to analyses various clinical studies which have been registered in www.clinicaltrials.gov and http://www.chictr.org.cn were registered with natural plant-based medicines and Traditional Chinese medicine (TCM) for discovering effective treatment and prevention of COVID-19. Total 46 and 64 natural drug and TCM interventions were identified which mainly determined the preventive strategies and possible treatments for COVID-19 infection. We identified that most of the clinical trial undergoing on natural compound like heparin and vitamin C as therapeutic agents and immune boosters for against COVID-19. Traditional Chinese medicines and herbal medicines can be effectively used as a preventive therapy against COVID-19 and after successful clinical trials and these potential therapies can be promoted by countries around the world. Supplementary InformationThe online version contains supplementary material available at (10.1007/s12088-020-00919-x).     

miRNAs; a novel strategy for the treatment of COVID-19

Coronavirus disease 2019 (COVID-19) is the seventh member of the bat severe acute respiratory syndrome family. COVID-19 can fuse their envelopes with the host cell membranes and deliver their genetic material. COVID-19 attacks the respiratory system and stimulates the host inflammatory responses, enhances the recruitment of immune cells, and promotes angiotensin-converting enzyme 2 activities. Patients with confirmed COVID-19 may have experienced fever, dry cough, headache, dyspnea, acute kidney injury, acute respiratory distress syndrome, and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID-19-associated mortality. However, these approaches may not be good treatment options. Therefore, the search for an alternative-novel therapy is urgently important to prevent the disease progression. Recently, microRNAs (miRNAs) have emerged as a promising strategy for COVID-19. The design of oligonucleotide against the genetic material of COVID-19 might suppress virus RNA translation. Several previous studies have shown that host miRNAs play an antiviral role and improve the treatment of patients with COVID-19. miRNAs by binding to the 3′-untranslated region (UTR) or 5′-UTR of viral RNA play an important role in COVID-19-host interplay and viral replication. miRNAs interact with multiple pathways and reduce inflammatory biomarkers, thrombi formation, and tissue damage to accelerate the patient outcome. The information in this review provides a summary of the current clinical application of miRNAs for the treatments of patients with COVID-19.     

Fighting against the second wave of COVID-19: Can honeybee products help protect against the pandemic?

Coronavirus Disease (COVID-19) has infected people in 210 nations and has been declared a pandemic on March 12, 2020 by the World Health Organization (WHO). In the absence of effective treatment and/or vaccines for COVID-19, natural products of known therapeutic and antiviral activity could offer an inexpensive, effective option for managing the disease. Benefits of products of honey bees such as honey, propolis, and bee venom, against various types of diseases have been observed. Honey bees products are well known for their nutritional and medicinal values, they have been employed for ages for various therapeutic purposes. In this review, promising effects of various bee products against the emerging pandemic COVID-19 are discussed. Products of honey bees that contain mixtures of potentially active chemicals, possess unique properties that might help to protect, fight, and alleviate symptoms of COVID-19 infection.     

Role of biochemical markers in the monitoring of COVID-19 patients

COVID-19 is an infectious disease caused by the SARSCoV-2 virus, which has given rise to a global sanitary emergency. The clinical characteristics of COVID-19 are varied and can range from an asymptomatic infection to a mild to severe pneumonia. Recent studies have shown that different laboratory parameters become altered in these patients, and as such are useful as biomarkers to assess the progression of the disease and categorize patients that may present a severe and/or fatal clinical condition. This review analyzes biochemical and immunological markers that become altered in COVID-19 patients and their impact on different organs at a hepatic, cardiac, renal and pancreatic level, as well as markers of inflammation, analyzing their implications in the evolution of the disease.     

Inefficiency of Sera from Mice Treated with Pseudotyped SARS-CoV to Neutralize 2019-nCoV Infection

The novel coronavirus 2019-nCoV has caused the pandemic of Wuhan pneumonia recently, posing a serious threat to global public health, and thus calling for the development of therapeutics and prophylactics. Here we showed that high titer anti-SARS-CoV spike protein serum cannot effectively neutralize 2019-nCoV infection. Based on our previous research, we developed SARS pseudovirus (SARS-PsV) and MERS pseudovirus (MERS-PsV) as immunogens to immunize mice. We found sera from mice treated with SARS-CoV S protein could potently cross-neutralize infection by SARS-CoV (50% neutralizing antibody titers, NT50 > 40, 000) and SARS-related coronavirus (NT50 > 7, 000), but weakly for 2019-nCoV infection NT50 < 100), implying that it may not be practical to treat 2019-nCoV infection with anti-SARS-CoV antibodies and that people with history of SARS-CoV infection many years ago may not be resistant to 2019-nCoV infection.     

Coronavirus and co-infections: A Saudi Arabian perspective

Mortality due to infectious diseases continues to rise globally, despite advances in antimicrobial therapy and supportive care. This is evident with the occurrence of coronavirus disease 2019 (COVID-19) pandemic, instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Saudi Arabia, an eminent country within the Arab region, has had significant impact during global pandemics, concomitant with the fact that millions of Muslims travel to Saudi Arabia for pilgrimages every year. Herein, we discuss the significance of SARS-CoV-1, SARS-CoV-2, as well as the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia with particular reference to global transmission and/or emergence of new variants due to genetic mixing of different strains. Furthermore, we also discuss the role of Saudi Arabia with reference to novel emerging infectious diseases and re-emerging infections, such as Ebola, zika, and monkeypox, as well as in the context on coinfections. Future strategies to limit the spread of viral infections and the pivotal role of Saudi Arabia, are deliberated upon.     

Cytokine storm intervention in the early stages of COVID-19 pneumonia

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30^th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.     

Tea crude extracts effectively inactivate severe acute respiratory syndrome coronavirus 2

It is well known that black and green tea extracts, particularly polyphenols, have antimicrobial activity against various pathogenic microbes including viruses. However, there is limited data on the antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged rapidly in China in late 2019 and which has been responsible for coronavirus disease 2019 (COVID-19) pandemic globally. In this study, 20 compounds and three extracts were obtained from black and green tea and found that three tea extracts showed significant antiviral activity against SARS-CoV-2, whereby the viral titre decreased about 5 logs TCID₅₀ per ml by 1·375 mg ml⁻¹ black tea extract and two-fold diluted tea bag infusion obtained from black tea when incubated at 25°C for 10 s. However, when concentrations of black and green tea extracts were equally adjusted to 344 µg ml⁻¹, green tea extracts showed more antiviral activity against SARS-CoV-2. This simple and highly respected beverage may be a cheap and widely acceptable means to reduce SARS-CoV-2 viral burden in the mouth and upper gastrointestinal and respiratory tracts in developed as well as developing countries.