Covid-19 pandemic outburst in Saudi Arabia: A glimpse

SynopsisSevere Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2) provoked alertness globally. Existing pandemic eruption of infections with SARS-CoV2 has been phrased as coronavirus disease 2019 (covid-19). Worldwide pneumonia outburst attributable to new SARS-CoV2 alleged to be originated in Wuhan city of China and has affectation of enormous danger regarding civic wellbeing. As of 11 March 2020, international death toll owing to outburst of new coronavirus was approximately 3,800, and about 110,000 have been declared as confirmed cases. The novel SARS-CoV2 demonstrated competence with respect to human to human communication; therefore depicted exponential intensification of cases. As of March 23, there are 374,513 collective cases of global infections; more than 16,350 deaths and number of recovered cases is 101,554. Now Europe has turn out into new epicenter of lethal coronavirus.More than one third of the covid 19 cases are currently outside China. Presently Italy is one of worst hit countries followed by Spain. The rapid global widespread of novel covid-19 viruses lead to World Health Organization (WHO) to declare outbreak as pandemic. Given to seriousness of present scenario an accurate and rapid classification of noxious pathogenic virus is important which will lend a hand in opting for best fitting drugs. The screening program will aid saving people’s lives and help to put off the pandemic situation. The scientists and researchers should collaborate nationally and internationally to win the battle against novel covid-19. We aimed to represent covid 19 outburst scenario in general and Saudi Arabia in particular. This short review report very briefly highlights covid-19 syndromes; propagation; Middle East outburst, natural products as cure for viral diseases, probable psychosomatic effects, protective measures and Islamic wisdom. SARS-CoV2 is subsequent coronavirus outburst that perturbs Middle East, after SARS-CoV and MERS-CoV which has been originated in kingdom of Saudi Arabia in year 2002 and 2012 respectively. The report covers information and developments till 23rd of March 2020 on basis of current published data and studies published on different scientific web-pages.     

The Role of Animal Research in Pandemic Responses

The significant advances made by the global scientific community during the COVID-19 pandemic, exemplified by the development of multiple SARVS-CoV-2 vaccines in less than 1 y, were made possible in part because of animal research. Historically, animals have been used to study the characterization, treatment, and prevention of most of the major infectious disease outbreaks that humans have faced. From the advent of modern ‘germ theory’ prior to the 1918 Spanish Flu pandemic through the more recent Ebola and Zika virus outbreaks, research that uses animals has revealed or supported key discoveries in disease pathogenesis and therapy development, helping to save lives during crises. Here we summarize the role of animal research in past pandemic and epidemic response efforts, as well as current and future considerations for animal research in the context of infectious disease research.

From the moment it began in late 2019, the COVID-19 pandemic has been met with remarkable scientific effort. In less than 1 y, substantial progress has been made in understanding the behavior of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, characterizing the damage it inflicts on the body, and developing safe and effective vaccines. Research in animals has provided many breakthroughs, as it has for most significant outbreaks in the past. Animals have been used to study infectious diseases long before disease-causing microorganisms were known to exist. Animal research in response to pandemics, past and present, provides a clear example of how such research can best serve the scientific community in the event of future outbreaks and other disease conditions. Response to a pandemic requires quick action to identify the emerging diseases, characterize transmission and pathogenesis, and develop preventative measures and therapies. Ideally, through the surveillance of environments and animal populations that may harbor pathogens with pandemic potential and through preclinical and basic science research in virology and vaccinology for diseases that are suspected to be potential threats, the pandemic response should begin before a disease gains the ability to spread easily through a population. In this article, we discuss the importance of animal research in all aspects of pandemic research response and the vital role it continues to play today.     

The significance of advanced COVID-19 diagnostic testing in pandemic control measures

During the 2 years since the start of the novel coronavirus disease 2019 (COVID-19) pandemic, the scientific world made an enormous effort to fight against this disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has high transmissibility. Advancements in vaccine and treatment strategies have reduced both the hospitalization and mortality rates. However, the virus has shown its ability to evolve and evade from our COVID-19 combating armamentaria by the most common evolution mechanism—mutation. Diagnostic testing has been the first line of defense following the identification of the causative agent. Ever since, the scientific community has developed nuclei acid-based, antigen-based, and antibody-based diagnostic tests, and these testing methodologies are still playing a central role in slowing down viral transmission. These testing methods have different sensitivity and specificity and could be optimally used in areas facing different challenges owing to different level and conditions of COVID-19 outbreak. In this review, we discuss these testing methodologies as well as the considerations on how to apply these diagnostic tests optimally in the community to cope with the ever-changing pandemic conditions.     

Should we be concerned about COVID-19 with nonhuman primates?

The coronavirus disease 2019 pandemic has radically changed the human activities worldwide. Although we are still learning about the disease, it is necessary that primatologists, veterinarians, and all that are living with nonhuman primates (NHP) be concerned about the probable health impacts as these animals face this new pandemic. We want to increase discussion with the scientific community that is directly involved with these animals, because preliminary studies report that NHP may become infected and develop symptoms similar to those in human beings.     

Prejudice in science – Lessons from the coronavirus story

In the current pandemic times, medical physicists may not be aware that there is an interesting story on two significant discoveries related to the coronavirus. One is the invention of the polymerase chain reaction (PCR) and the other is the first electron microscopic observation and identification of the coronavirus. Both of them were disregarded by the reviewers and major journals declined to publish these discoveries. These days, PCR, for example, is a widespread method for analyzing DNA, having a profound effect on healthcare, especially now during the Covid-19 pandemic. Prejudice or perhaps ignorance prevail in every aspect of our society, and there is no exception in scientific research. We need to, however, learn from these two stories and be open-minded about novel discoveries and findings – as they may be just disruptive in the “right” way to lead to an unexpected breakthrough.     

COVID-19: Antiviral agents and enzyme inhibitors/receptor blockers in development

Novel 2019 coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and coronavirus disease 2019 (COVID-19), the respiratory syndrome it causes, have shaken the world to its core by infecting and claiming the lives of many people since originating in December 2019 in Wuhan, China. World Health Organization and several states have declared a pandemic situation and state of emergency, respectively. As there is no treatment for COVID-19, several research institutes and pharmaceutical companies are racing to find a cure. Advances in computational approaches have allowed the screening of massive antiviral compound libraries to identify those that may potentially work against SARS-CoV-2. Antiviral agents developed in the past to combat other viruses are being repurposed. At the same time, new vaccine candidates are being developed and tested in preclinical/clinical settings. This review provides a detailed overview of select repurposed drugs, their mechanism of action, associated toxicities, and major clinical trials involving these agents.     

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world''s adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.     

Human Organoids as a Promising Platform for Fighting COVID-19

The coronavirus disease 2019 (COVID-19) global pandemic evoked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a major public health problem with significant morbidity and mortality. Understanding the pathogenesis and molecular mechanisms underlying this novel virus is crucial for both fundamental research and clinical trials in order to devise effective therapies and vaccination regimens. Basic research on SARS-CoV-2 largely depends on ex vivo models that allow viral invasion and replication. Organoid models are now emerging as a valuable tool to investigate viral biology and disease progression, serving as an efficient platform to investigate potential therapies for COVID-19. Here, we summarize various human stem cell-derived organoid types employed in SARS-CoV-2 studies. We highlight key findings from these models, including cell tropisms and molecular mechanisms in viral infection. We also describe their use in identifying potential therapeutic agents against SARS-CoV-2. As more and more advanced organoids emerge, they will facilitate the understanding of disease pathogenesis for drug development in this dreaded pandemic.     

Severe Acute Respiratory Syndrome Coronavirus 2: Manifestations of Disease and Approaches to Treatment and Prevention in Humans

The coronavirus disease 2019 (COVID-19) pandemic was caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus has challenged civilization and modern science in ways that few infectious diseases and natural disasters have previously, causing globally significant human morbidity and mortality and triggering economic downturns across financial markets that will be dealt with for generations. Despite this, the pandemic has also brought an opportunity for humanity to come together and participate in a shared scientific investigation. Clinically, SARS-CoV-2 is associated with lower mortality rates than other recently emerged coronaviruses, such as SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). However, SARS-CoV-2 exhibits efficient human-to-human spread, with transmission often occurring before symptom recognition; this feature averts containment strategies that had worked previously for SARS-CoV and MERS-CoV. Severe COVID-19 disease is characterized by dysregulated inflammatory responses associated with pulmonary congestion and intravascular coagulopathy leading to pneumonia, vascular insults, and multiorgan disease. Approaches to treatment have combined supportive care with antivirals, such as remdesivir, with immunomodulatory medications, including corticosteroids and cytokine-blocking antibody therapies; these treatments have advanced rapidly through clinical trials. Innovative approaches to vaccine development have facilitated rapid advances in design, testing, and distribution. Much remains to be learned about SARS-CoV-2 and COVID-19, and further biomedical research is necessary, including comparative medicine studies in animal models. This overview of COVID-19 in humans will highlight important aspects of disease, relevant pathophysiology, underlying immunology, and therapeutics that have been developed to date.

In December 2019, a cluster of cases of pneumonia without a clear etiology occurred in Wuhan, China. With remarkable speed and efficiency, the etiology of this illness was soon identified as a novel coronavirus; the complete viral genome was sequenced and published on January 10, 2020.¹⁸² These events introduced the world to coronavirus disease 2019 (COVID-19). The disease, now known to be caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into the most significant pandemic of recent times. In less than a year since the virus was first recognized, multiple candidate vaccines were developed worldwide, and some of them rapidly progressed to clinical trials and widespread administration. As the pandemic continues, a number of sequence variants of the virus have emerged around the world. This continued viral evolution highlights the need for continued biomedical research to facilitate understanding of the pathogenesis of COVID-19, seeking innovative therapeutic and preventative strategies for the current and possibly future pandemics. This article will review aspects of SARS-CoV-2 infection of humans and COVID-19, focusing on important aspects of clinical disease, pathophysiology, immunology, and the development of therapeutic and preventative measures to provide context for discussion of the animal models used to study SARS-CoV-2 and COVID-19.     

Important Management Considerations In Patients With Pituitary Disorders During The Time Of The Covid-19 Pandemic

Objective: In December 2019, a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak of coronavirus disease 2019 (COVID-19) that resulted in a global pandemic with substantial morbidity and mortality. Currently, there is no specific treatment or approved vaccine against COVID-19. The underlying associated comorbidity and diminished immune function of some pituitary patients (whether caused by the disease and its sequelae or treatment with excess glucocorticoids) increases their risk of contracting and developing complications from COVID-19 infection.Methods: A review of studies in PubMed and Google Scholar published between January 2020 to the time of writing (May 1, 2020) was conducted using the search terms ‘pituitary,’ ‘coronavirus,’ ‘COVID-19’, ‘2019-nCoV’, ‘diabetes mellitus’, ‘obesity’, ‘adrenal,’ and ‘endocrine.’Results: Older age and pre-existing obesity, hypertension, cardiovascular disease, and diabetes mellitus increase the risk of hospitalization and death in COVID-19 patients. Men tend to be more severely affected than women; fortunately, most men, particularly of younger age, survive the infection. In addition to general comorbidities that may apply to many pituitary patients, they are also susceptible due to the following pituitary disorder–specific features: hypercortisolemia and adrenal suppression with Cushing disease, adrenal insufficiency and diabetes insipidus with hypopituitarism, and sleep-apnea syndrome and chest wall deformity with acromegaly.Conclusion: This review aims to focus on the impact of COVID-19 in patients with pituitary disorders. As most countries are implementing mobility restrictions, we also discuss how this pandemic has affected patient attitudes and impacted our decision-making on management recommendations for these patients.Abbreviations: ACE = angiotensin-converting enzyme; AI = adrenal insufficiency; ARB = angiotensin receptor blocker; ARDS = acute respiratory disease syndrome; COVID-19 = coronavirus disease 2019; CPAP = continuous positive airway pressure; DI = diabetes insipidus; DM = diabetes mellitus; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2     

Targeting papain-like protease for broad-spectrum coronavirus inhibition

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13238-022-00909-3.     

Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements

SARS-CoV-2 is a betacoronavirus with a linear single-stranded, positive-sense RNA genome, whose outbreak caused the ongoing COVID-19 pandemic. The ability of coronaviruses to rapidly evolve, adapt, and cross species barriers makes the development of effective and durable therapeutic strategies a challenging and urgent need. As for other RNA viruses, genomic RNA structures are expected to play crucial roles in several steps of the coronavirus replication cycle. Despite this, only a handful of functionally-conserved coronavirus structural RNA elements have been identified to date. Here, we performed RNA structure probing to obtain single-base resolution secondary structure maps of the full SARS-CoV-2 coronavirus genome both in vitro and in living infected cells. Probing data recapitulate the previously described coronavirus RNA elements (5′ UTR and s2m), and reveal new structures. Of these, ∼10.2% show significant covariation among SARS-CoV-2 and other coronaviruses, hinting at their functionally-conserved role. Secondary structure-restrained 3D modeling of these segments further allowed for the identification of putative druggable pockets. In addition, we identify a set of single-stranded segments in vivo, showing high sequence conservation, suitable for the development of antisense oligonucleotide therapeutics. Collectively, our work lays the foundation for the development of innovative RNA-targeted therapeutic strategies to fight SARS-related infections.     

Coronavirus disease 2019 pandemic and allogeneic hematopoietic stem cell transplantation: a single center reappraisal

Background: The coronavirus disease 2019 (COVID-19) pandemic has deeply modified the complex logistical process underlying allogeneic hematopoietic stem cell transplant practices. Aim: In light of these changes, the authors compared data relative to allogeneic transplants carried out from 2018 at their center before (n = 167) and during the pandemic (n = 45). Methods: The authors examined patient characteristics, donor and graft types, cell doses and main transplant outcomes. Moreover, the authors evaluated the rise of costs attributable to additional COVID-19-related procedures as well as the risk of adverse events these procedures conveyed to grafts or recipients. Results: Overall, the number of transplants did not decrease during the pandemic, whereas patients at high relapse risk were prioritized. Transplants were mainly from matched unrelated donors, with a significant decrease in haploidentical related donors. Moreover, the use of bone marrow as a graft for haploidentical transplant was almost abandoned. Cryopreservation was introduced for all related and unrelated apheresis products, with a median storage time of 20 days. Notably, transplant outcomes (engraftment, acute graft-versus-host disease and non-relapse mortality) with cryopreserved products were comparable to those with fresh products. Conclusions: Considering that the emergency situation may persist for months, cryopreserving allogeneic grafts can offer a lifesaving opportunity for patients whose allogeneic transplant cannot be postponed until after the end of the COVID-19 pandemic.     

Induced pluripotent stem cell-based disease modeling and prospective immune therapy for coronavirus disease 2019

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a never before seen challenge to human health and the economy. Considering its clinical impact, with no streamlined therapeutic strategies in sight, it is crucial to understand the infection process of SARS-CoV-2. Our limited knowledge of the mechanisms underlying SARS-CoV-2 infection impedes the development of alternative therapeutics to address the pandemic. This aspect can be addressed by modeling SARS-CoV-2 infection in the human context to facilitate drug screening and discovery. Human induced pluripotent stem cell (iPSC)-derived lung epithelial cells and organoids recapitulating the features and functionality of the alveolar cell types can serve as an in vitro human model and screening platform for SARS-CoV-2. Recent studies suggest an immune system asynchrony leading to compromised function and a decreased proportion of specific immune cell types in coronavirus disease 2019 (COVID-19) patients. Replenishing these specific immune cells may serve as useful treatment modality against SARS-CoV-2 infection. Here the authors review protocols for deriving lung epithelial cells, alveolar organoids and specific immune cell types, such as T lymphocytes and natural killer cells, from iPSCs with the aim to aid investigators in making relevant in vitro models of SARS-CoV-2 along with the possibility derive immune cell types to treat COVID-19.     

In silico evaluation of flavonoids as effective antiviral agents on the spike glycoprotein of SARS-CoV-2

The novel coronavirus pandemic has spread over in 213 countries as of July 2020. Approximately 12 million people have been infected so far according to the reports from World Health Organization (WHO). Preventive measures are being taken globally to avoid the rapid spread of virus. In the current study, an in silico approach is carried out as a means of inhibiting the spike protein of the novel coronavirus by flavonoids from natural sources that possess both antiviral and anti-inflammatory properties. The methodology is focused on molecular docking of 10 flavonoid compounds that are docked with the spike protein of SARS-CoV-2, to determine the highest binding affinity at the binding site. Molecular dynamics simulation was carried out with the flavonoid-protein complex showing the highest binding affinity and highest interactions. The flavonoid naringin showed the least binding energy of −9.8 Kcal/mol with the spike protein which was compared with the standard drug, dexamethasone which is being repurposed to treat critically ill patients. MD simulation was carried out on naringin-spike protein complex for their conformational stability in the active site of the novel coronavirus spike protein. The RMSD of the complex appeared to be more stable when compared to that of the protein from 0.2 nm to 0.4 nm. With the aid of this in silico approach further in vitro studies can be carried out on these flavonoids against the novel coronavirus as a means of viral protein inhibitors.     

The psychological impact of the covid-19 pandemic on radiotherapy cancer patients

In March 2020, the World Health Organization (WHO) characterized the outbreak of the coronavirus disease 2019 (COVID-19) as a pandemic. The aim of this study was to evaluate the psychological impact of the COVID-19 pandemic on cancer patients undergoing radiotherapy.Were enrolled 210 patients in treatment and in follow-up who had access to the Radiation Oncology Department of the Campus Bio-Medico University Hospital Foundation between April and May 2020. The sample was subjected to structured interview and validated questionnaires. 37% of patients showed significant levels of distress; depressive symptoms were reported by 22.4% of patients and 99% of sample had clinically significant anxiety symptoms. All patients anxiety worsened during the COVID-19 pandemic (p=< 0.001). Patients on active treatment had higher levels of distress (3.5 vs 2.6; p = 0.04) and anxiety (3.5 vs 2.6; p = 0.04). Lung cancer patients appeared to be more afraid of COVID-19 than other patients (24.2 vs 22.2). This study highlights the presence of clinically significant anxiety in 99% of sample. This conclusion reflects the condition of emotional distress present during the pandemic which makes it necessary to treat patients in a multidisciplinary perspective that includes psychological support in the care plan.     

Summary of the Detection Kits for SARS-CoV-2 Approved by the National Medical Products Administration of China and Their Application for Diagnosis of COVID-19

Virologica Sinica - The on-going global pandemic of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been...     

Focus: Zoonotic Disease: The Tragedy of Names

The naming of pathogens and their associated syndromes is a thorny process which unfolds in a complex geopolitical environment. This brief piece offers perspective on the multitude of forces that shape the name of a pathogen and summarizes the story of Sin Nombre Virus, with some reference to the ongoing saga of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A monopoly on names and circulating monikers rarely exists, and certain communities become disproportionately impacted by misunderstandings or stigmatization. By acknowledging these processes, we can better serve as allies to affected communities dealing with both pandemic and prejudice.     

COVID-19: Antiviral Agents,Antibody Development and Traditional Chinese Medicine

Virologica Sinica - The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) is the first pandemic caused by coronavirus named severe acute respiratory syndrome...     

COVID-19 Pandemic and Male Fertility: Clinical Manifestations and Pathogenic Mechanisms

Biochemistry (Moscow) - The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency...