SARS-CoV Coronavirus Research Articles

Post-COVID-19 Infection and Cognitive Deficits: Permanent or Transient?

COVID-19 can be defined as an infectious disease caused by the new coronavirus (Sars-Cov2). The main signs responsible for evinced by the patients are fever, myalgia, dyspnea, and disorders of taste and smell. An array of additional disorders, characterize it as a systemic disease. Nasal congestion, memory deficits, headache, conjunctivitis, pharyngitis, diarrhea, dysautonomia and impairment of diverse organs and systems have been reported. These manifestations may be mild and sometimes asymptomatic, but can also result in death [1,2]. Varying degrees of injury may be manifest in the peripheral and central nervous systems (CNS). Two routes of entry into the CNS are already known; a hematogenous pathway mediated by ACE2 receptors, and retrograde neuronal retrograde pathways. These neuropathic mechanisms may explain the increased occurrence of stroke, behavioral changes, and anosmia [3,5].

Accelerated Development of COVID-19 Vaccines: Technology Platforms, Benefits, and Associated Risks.

Multiple preventive COVID-19 vaccines have been developed during the ongoing SARS coronavirus (CoV) 2 pandemic, utilizing a variety of technology platforms, which have different properties, advantages, and disadvantages. The acceleration in vaccine development required to combat the current pandemic is not at the expense of the necessary regulatory requirements, including robust and comprehensive data collection along with clinical product safety and efficacy evaluation. Due to the previous development of vaccine candidates against the related highly pathogenic coronaviruses SARS-CoV and MERS-CoV, the antigen that elicits immune protection is known: the surface spike protein of SARS-CoV-2 or specific domains encoded in that protein, e.g., the receptor binding domain. From a scientific point of view and in accordance with legal frameworks and regulatory practices, for the approval of a clinic trial, the Paul-Ehrlich-Institut requires preclinical testing of vaccine candidates, including general pharmacology and toxicology as well as immunogenicity. For COVID-19 vaccine candidates, based on existing platform technologies with a sufficiently broad data base, pharmacological–toxicological testing in the case of repeated administration, quantifying systemic distribution, and proof of vaccination protection in animal models can be carried out in parallel to phase 1 or 1/2 clinical trials. To reduce the theoretical risk of an increased respiratory illness through infection-enhancing antibodies or as a result of Th2 polarization and altered cytokine profiles of the immune response following vaccination, which are of specific concern for COVID-19 vaccines, appropriate investigative testing is imperative. In general, phase 1 (vaccine safety) and 2 (dose finding, vaccination schedule) clinical trials can be combined, and combined phase 2/3 trials are recommended to determine safety and efficacy. By applying these fundamental requirements not only for the approval and analysis of clinical trials but also for the regulatory evaluation during the assessment of marketing authorization applications, several efficacious and safe COVID-19 vaccines have been licensed in the EU by unprecedentedly fast and flexible procedures. Procedural and regulatory–scientific aspects of the COVID-19 licensing processes are described in this review.

Modelamiento del compromiso laboral ante la COVID-19 en un hospital público del centro de México

Objetivos: modelar los indicadores del compromiso laboral considerando la exposición al contagio debido a la transmisión comunitaria de la pandemia en una institución de salud pública.
 Métodos: se estudiaron las dimensiones psicométricas en una observación transversal con una muestra de 100 practicantes profesionales y servidores sociales en una institución de salud asignada a la atención de la pandemia. Se utilizó la Escala de Compromiso Laboral de Carreón (2021) la cual mide siete dimensiones: social, sectorial, académico, formativo, familiar, profesional y personal.
 Resultados: se confirmó una estructura factorial de siete componentes principales que explicaron el 53% de la varianza total, aunque no fue incluido el compromiso gremial como un factor que explica la disposición favorable al conservar el prestigio de la carrera que se estudió.
 Conclusiones: se recomienda el contraste del modelo con la inclusión el compromiso gremial a fin de poder incrementar la varianza total explicada y anticipar un escenario de respuesta ante otra crisis sanitaria como un rebrote del COVID-19.

Pathomorphology of spontaneous coronaviral infection with SARSCоV-2 in maine coon kittens

Pathological diagnostics is a mandatory and one of the most important methods for diagnosing animal diseases. Competent use of the methods of pathological and histological diagnostics allows in the shortest possible time to make the correct preliminary diagnosis, to carry out complicating diseases, and additional laboratory tests in a timely manner. At the same time, the pathological and morphological changes in the body of animals with a new zoonotic disease, COVID-19, have not been sufficiently studied or are not studied at all. This paper describes the pathological processes and histological changes in maine coon kittens with spontaneous SARSCoV-2 coronavirus infection. The obtained research results are presented in the form of detailed pathological and histological diagnoses. It has been established that the leading structural changes in kittens’ bodies are characterized by the development of congenital and postnatal malnutrition, the predominance of profound disorders of the respiratory and cardiovascular systems: alveolar emphysema of the anterior and middle lobes of the lungs with areas of atelectasis and small focal interstitial pneumonia in them, atelectasis of the caudal lobes of the lungs (in kittens 1–2 days of age); alveolar emphysema, edema (“carmine lungs”) of the lungs, large-focal interstitial pneumonia, sclerotization of the lungs with localization in the diaphragmatic lobes (at 10–14 days of age); acute expansion of the heart; acute venous hyperemia and edema of internal organs; pronounced postmortem blood coagulation in the cavities of the heart, large arteries and veins. Complicating processes are granular and small-droplet fatty degeneration of parenchymal organs, the development of which, apparently, is due to a combination of hemodynamic disturbances, prolonged hypoxia and intoxication of the animal body. Considering the severity and depth of structural disorders, primarily in the lungs of newborn animals, it can be concluded that the kittens are infected vertically (transplacentally).

The Role of Regional Anesthesia During the SARS-CoV2 Pandemic: Appraisal of Clinical, Pharmacological and Organizational Aspects.

The severe acute respiratory syndrome coronavirus SARS-CoV2 is spreading over millions of people worldwide, leading to thousands of deaths, even among the healthcare providers. Italy has registered the deaths of 337 physicians and more than 200 nurses as of March 14, 2021. Anesthesiologists are at higher risk as they are the care providers in both ICU and operating rooms.Although the vaccination of healthcare providers has been the prioirity, physicians are still continually exposed to the virus and potentially risk contagion and must thus protect themselves and their patients from the risks of infection while providing the best care to their surgical patients.Regional anesthesia allows for a reduction in airway manipulation, reducing environmental contamination as a result. Furthermore, regional anesthesia reduces the opioid requirements as well as the muscle paralysis due to muscle-relaxants and should be recommended whenever possible in COVID-19 patients. Our aim is to evaluate the advantages and criticisms of regional anesthesia in the management of surgical patients in the pandemic age.

Change in Diet Quality and Meal Sources During the COVID-19 Pandemic in a Subset of Men and Women in the Cancer Prevention Study-3

ObjectivesThe massive spread of the novel coronavirus SARS-CoV2 (COVID-19) and subsequent restrictive measures caused disruptions in daily routines and behaviors, including changes in diet that may have consequences on immediate health and longer term risk of chronic disease. Our objective was to assess two-year changes in diet quality among subgroups of the Cancer Prevention Study-3 (CPS-3) cohort.MethodsIn August 2020, an online COVID-19 survey that assessed food group intakes, meal sources, and COVID-related questions was completed by a subgroup of 2,335 CPS-3 participants. Paired t-tests evaluated reported change in behaviors from 2018 to 2020. A diet quality score assigned higher points for greater frequency of foods recommended by cancer prevention guidelines, and lower points for foods that are not recommended.ResultsWhile diet quality improved slightly, on average, from 2018 to 2020, consumption of component food groups decreased (P < 0.001),with the greatest decreases in vegetables and whole grains. The greatest decrease in vegetable intake occurred in Black participants, as well as participants who gained weight. On average, Asian/Pacific Islander participants increased fruit consumption. Participants who lost ≥20 pounds had the greatest decrease in refined grain consumption and greatest improvements in diet quality. Low diet quality scores during the pandemic were associated with being male, current smoking, less education, lower physical activity, higher BMI, and weight gain of ≥20 pounds since 2018. Participants who worried about food insecurity, were at high risk of COVID-19 complications, and reported more COVID-related stressors also had lower scores. Changes in diet quality did not appear to vary by other demographic factors. On average, total alcohol intake decreased in most groups examined. Frequency of meals from all sources decreased (P < 0.001), and the greatest decreases were observed in full-service restaurants and prepared ready-to-eat meals.ConclusionsUndesirable changes in diet during the pandemic, particularly decreases in vegetables and whole grains, may contribute to weight gain, poor metabolic health, and subsequent higher risk of chronic disease.Funding SourcesThe American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-3 Cohort.

Surface adhesion of viruses and bacteria: Defend only and/or vibrationally extinguish also?! A perspective.

Coronaviruses COVID-19, SARS-CoV and NL63 use spikes in their corona to bind to angiotensin converting enzyme 2 (ACE2) sites on cytoskeletal membranes of host cells to deliver their viral payload. While groups such as disulfides in ACE2’s zinc metallopeptidase, and also in COVID-19’s spikes, facilitate such binding, it is worth exploring how similar complementary sites on materials such as polymers, metals, ceramics, fabrics, and biomaterials promote binding of viruses and bacteria and how they could be further engineered to prevent bioactivity, or to act as agents to collect viral payloads in filters or similar devices. In that vein, this article offers a perspective on novel tools and approaches for chemically and topologically modifying most utilitarian surfaces via defensive topological vibrational engineering to either prevent such adhesion or to enhance adhesion and elicit vibrational characteristics/’musical signatures’ from the surfaces so that the structure of the binding sites of viruses and bacteria is permanently altered and/or their cellular machinery is permanently disabled by targeted chemical transformations.Graphic abstract Supplementary InformationThe online version contains supplementary material available at 10.1557/s43580-021-00079-0.

PECULIARITIES OF CORONAVIRUS INFECTION CLINICAL COURSE CAUSED BY SARS-COV-2 IN NEWBORNS

A lot of data concerning the epidemiological features of the pathogen, clinical andparaclinical characteristics of the disease, principles of diagnosis and approaches tothe treatment have been published in the scientific literature during the year of pandemiacaused by SARS-CoV-2. But still there are many unresolved issues regarding theepidemiological and clinical characteristics of this coronavirus infection in newborns.Purpose – to conduct observational study of the peculiarities of SARS-CoV-2 coronavirusinfection in newborns treated during 2020 on the basis of RCNE "Chernivtsi RegionalChildren's Clinical Hospital", Chernivtsi.Material and methods. Analysis of medical records of 12 inpatient newborns wasconducted retrospectively to achieve the goal of the study. Inclusion criteria: age 0-28days of life, confirmed by positive test of polymerase chain reaction (PCR) for SARSCoV-2 coronavirus infection of a nasopharyngeal smear. The average age of childrenat the time of admission was 13.6 ± 2.1 days, every third newborn child (33.3%) wasadmitted before the age of 10 days old. The portion of rural residents was 66.6%, girls(75%) predominated among children who fell ill.Results. It has been revealed that in most cases the contact of newborns with COVID-19patients was confirmed. Mostly children were admitted from home on average onthe second day after the onset of the disease, predominantly with the typical clinicalsymptoms of acute respiratory viral infection, at the onset of the disease gastrointestinalmanifestations prevailed in only two of patients. The course of the disease was favorable.Conclusions. The detected changes in the follow-up infants’ complete blood count requirefurther dynamic clinical and paraclinical observation.

Interim Guidelines on the Screening, Assessment and Clinical Management of Pediatric Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19)

The emergence of the novel coronavirus SARSCoV-2 and the subsequent declaration by the World Health Organization of the coronavirus disease 2019 (COVID-19) pandemic has greatly impacted the lives of many all over the world. As the total number of reported cases increase globally, the number of pediatric cases have also steadily increased over the past several months. This has led to an expansion of scientific and clinical knowledge on COVID-19 in children.

Meticulous assessment of natural compounds from NPASS database for identifying analogue of GRL0617, the only known inhibitor for SARS-CoV2 papain-like protease (PLpro) using rigorous computational workflow.

The latest global outbreak of 2019 respiratory coronavirus disease (COVID-19) is triggered by the inception of novel coronavirus SARS-CoV2. If recent events are of any indicators of the epidemics of past, it is undeniable to state a fact that the SARS-CoV2 viral infection is highly transmissible with respect to its previously related SARS-CoV’s. Papain-like protease (PLpro) is an enzyme that is required by the virus itself for replicating into the host system; and it does so by processing its polyproteins into a functional replicase complex. PLpro is also known for downregulating the genes responsible for producing interferons, an essential family of molecules produced in response to viral infection, thus making this protein an indispensable drug target. In this study, PLpro inhibitors were identified through high throughput structure-based virtual screening approach from NPASS natural product library possessing ~ 35,000 compounds. Top five hits were scrutinised based on structural aromaticity and ability to interact with a key active site residue of PLpro, Tyr268. For second level of screening, the MM-GBSA End-Point Binding Free Energy Calculation of the docked complexes was performed, which identified Caesalpiniaphenol A as the best hit. Caesalpiniaphenol A not only possess a double ring aromatic moiety but also has lowest minimum binding energy, which is at par with the control GRL0617, the only known inhibitor of SARS-CoV2 PLpro. Details of the Molecular Dynamics (MD) simulation and ADMET analysis helped to conclusively determine Caesalpiniaphenol A as potentially an inhibitor of SARS-CoV2 PLpro.Graphic abstract

Evolution of SARS CoV-2 Coronavirus Surface Protein Investigated with Mass Spectrometry Based Phylogenetics

The evolution of the SARS-CoV2 coronavirus S-protein is studied using a mass spectrometry based protein phylogenetic approach (known as phylonumerics). This is achieved using mass maps generated for the surface S-protein across various strains, including new variants, to construct phylogenetic trees. The trees are built solely from these numerical datasets through a pairwise comparison of mass values from each protein set. Single point mutations are calculated from peptide mass differences across different sets and these are displayed at the branch nodes on the trees in a single step tree-building step. The topology of the trees is studied with different protein coverages and the mutations identified are compared with those derived from the sequence data. It is demonstrated that most non-synonymous mutations can be correctly identified from the mass data alone, thus avoiding the need for gene or protein sequencing, and any sequence alignment, that are required by other phylogenetic approaches.

Computational optimization of the SARS-CoV-2 receptor-binding-motif affinity for human ACE2

The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 2019 pandemic, and the closely related SARS-CoV coronavirus enter cells by binding at the human angiotensin converting enzyme 2 (hACE2). The stronger hACE2 affinity of SARS-CoV-2 has been connected with its higher infectivity. In this work, we study hACE2 complexes with the receptor-binding domains (RBDs) of the human SARS-CoV-2 and human SARS-CoV viruses, using all-atom molecular dynamics simulations and computational protein design with a physics-based energy function. The molecular dynamics simulations identify charge-modifying substitutions between the CoV-2 and CoV RBDs, which either increase or decrease the hACE2 affinity of the SARS-CoV-2 RBD. The combined effect of these mutations is small, and the relative affinity is mainly determined by substitutions at residues in contact with hACE2. Many of these findings are in line and interpret recent experiments. Our computational protein design calculations redesign positions 455, 493, 494, and 501 of the SARS-CoV-2 receptor binding motif, which contact hACE2 in the complex and are important for ACE2 recognition. Sampling is enhanced by an adaptive importance sampling Monte Carlo method. Sequences with increased affinity replace CoV-2 glutamine by a negative residue at position 493; serine by a nonpolar or aromatic residue or an asparagine at position 494; and asparagine by valine or threonine at position 501. Substitutions at positions 455 and 501 have a smaller effect on affinity. Substitutions suggested by our design are seen in viral sequences encountered in other species, including bat and pangolin. Our results might be used to identify potential virus strains with higher human infectivity and assist in the design of peptide-based or peptidomimetic compounds with the potential to inhibit SARS-CoV-2 binding at hACE2.

A New Pandemic Coronavirus COVID-19 Evolutionary Relation,Transmission, Infectivity and Immunity

The currently COVID-19 virus appeared in China in the beginning at December 2019, infected more than thousands of humans, by causing a severe respiratory disease (like pneumonia), in severe cases lead to death. Rapidly spread all over the world and cause apandemic as announced by the world health organization (WHO), this virus showed a close evolutionary relation to other type of coronavirus, the sever acute respiratory syndrome coronavirus SARS-CoV, which is responsible for the endemic that appeared in 2002-2003. In this review it was been focused on the causes of the pandemic as well as study the results of the latest research in connection with the previous publications and the role of molecular genetic analysis study of the viral RNA to get more knowledge about the evolutionary relation, infectivity and immunity.

The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways.

The high transmissibility of SARS-CoV-2 is related to abundant replication in the upper airways, which is not observed for the other highly pathogenic coronaviruses SARS-CoV and MERS-CoV. We here reveal features of the coronavirus spike (S) protein, which optimize the virus towards the human respiratory tract. First, the S proteins exhibit an intrinsic temperature preference, corresponding with the temperature of the upper or lower airways. Pseudoviruses bearing the SARS-CoV-2 spike (SARS-2-S) were more infectious when produced at 33°C instead of 37°C, a property shared with the S protein of HCoV-229E, a common cold coronavirus. In contrast, the S proteins of SARS-CoV and MERS-CoV favored 37°C, in accordance with virus preference for the lower airways. Next, SARS-2-S-driven entry was efficiently activated by not only TMPRSS2, but also the TMPRSS13 protease, thus broadening the cell tropism of SARS-CoV-2. Both proteases proved relevant in the context of authentic virus replication. TMPRSS13 appeared an effective spike activator for the virulent coronaviruses but not the low pathogenic HCoV-229E virus. Activation of SARS-2-S by these surface proteases requires processing of the S1/S2 cleavage loop, in which both the furin recognition motif and extended loop length proved critical. Conversely, entry of loop deletion mutants is significantly increased in cathepsin-rich cells. Finally, we demonstrate that the D614G mutation increases SARS-CoV-2 stability, particularly at 37°C, and, enhances its use of the cathepsin L pathway. This indicates a link between S protein stability and usage of this alternative route for virus entry. Since these spike properties may promote virus spread, they potentially explain why the spike-G614 variant has replaced the early D614 variant to become globally predominant. Collectively, our findings reveal adaptive mechanisms whereby the coronavirus spike protein is adjusted to match the temperature and protease conditions of the airways, to enhance virus transmission and pathology.

Exploring Dietary Behavior Changes Due to the COVID-19 Confinement in Colombia: A National and Regional Survey Study.

The aim of this study was to evaluate the impact of coronavirus SARS-Cov2 (COVID-19) confinement measures in Colombia on the dietary behaviors of a large population sample, at national and regional levels. A survey was conducted to assess dietary behaviors during the COVID-19 confinement. The survey involved 2,745 participants, aged 18 years or older, from six regions of the country (Atlántica, Bogotá, Central, Oriental, Orinoquía and Amazonía, and Pacífica). Dietary intake of foods and foods groups in grams per day before and during the confinement was estimated by considering standard serving sizes of foods. One-way ANOVA was used to analyze differences between the regions with regard to dietary behavior changes during the confinement. Differences were deemed significant at p-value < 0.05. Dietary patterns (DPs) before and during the confinement were derived from principal component analysis. Certain dietary habits were adopted by the study population during the confinement (e.g., higher frequency of snacking and home cooking), with significant differences by regions with regard to these habits, as well as regarding culinary processes. The levels of consumption of several foods also changed during the confinement, nationally and regionally. We identified three DPs before the confinement (protein-rich, carbohydrate-rich, and sugar foods patterns) and four DPs during the confinement (westernized, carbohydrate-rich, protein-rich, fish and fruits-vegetable patterns), with an explained total variance of 33 and 45%, respectively. The profile of these DPs varied to some extent between the regions; their adherence to each DP also varied (p-value < 0.001). Our results show that there were marked differences by regions in the dietary behaviors of this population during the confinement, with an overall trend toward unhealthier DPs. These results may help to shape public health nutrition interventions in Colombia during the COVID-19 pandemic and in a post-COVID stage.

Current Nutritional Support in Critical Ill Covid-19 Patients: A Brief Review

Covid-19 is a high prevalence of pneumonia of pathless cause in that started in 2019 in Wuhan, Hubei Province, China. Five to 10% of the coronavirus SARSCoV- 2-infected patients, i.e., with new coronavirus disease 2019 (COVID-19), are presenting with an Acute Respiratory Distress Syndrome (ARDS) requiring urgent respiratory and hemodynamic support in the Intensive Care Unit (ICU). However, nutrition is an important element of care. The nutritional assessment and the early nutritional care management of COVID-19 patients must be integrated into the overall therapeutic strategy. Absence of treatment for this new virus, finding alternative methods to prevent and control the disease is important. Having a well-functioning immune system is essential for the host’s defense against pathogenic organisms. Malnutrition can lead to an impaired immune system during life. Even though the immune system response to infection is itself a factor that could lead to nutritional status impairment. Deficiency of some nutrients can lead to disorders of immune system. Adequate intake of vitamins (A, D, Bs, C and E), minerals (selenium, zinc and iron) and omega-3 fatty acids are among the essential factors in proper immune system function and the international recommendations on nutrition in the ICU should be followed. Some specific issues about the nutrition of the COVID-19 patients in the ICU should be emphasized. We propose a flow chart and ten key issues for optimizing the nutrition management of COVID-19 patients in the ICU.

Youth Attitude and Perception during the Covid-19 contingency in Morelia, Michoacan

Introduction: The worldwide contingency for Covid-19 disease has caused substantial changes in the lifestyle of the population, modifying consumption habits, and perceptions of individuals. In the case of young people, the pandemic has revealed problems, needs, and challenges related to health, violence, education, and employment. Method: The objective of this study is to identify the perceptions of the young population aged 16 to 29 years in the city of Morelia, Michoacan, Mexico, during the health contingency of the Covid-19 disease generated by the new coronavirus SarsCov-2. The sample consists of 1386 cases, collected from May to July. The stratified sampling by quotas was used to ensure the representation of the entire young population in the metropolitan area of ​​the municipality. The measurement instrument consists of 48 questions divided into 5 elements: Perception of contingency, Physical and Mental Health, Education, Employment, and Consumption Habits. Results: In the study, 847 women and 539 men participated, being 61.1% of feminine gender and 38.9% masculine individuals; 84.9% of the participating individuals declared to pass the contingency with family members. The marital status of the participants is 87.7% single, 6.3% married, and 7.9% in concubinage. 20.6% of the respondents declared to be in charge of children, and 18.3% to be in charge of people over 65 years old. 65.9% of the participants declared to stay at home and only leave for specific situations; On the other hand, government official press conferences and social networks, followed by open and pay-tv have been the most used media to be informed. There is a strong interest in receiving information about Covid-19 and psychological care, as well as receiving consultations and medicines at home, also the main concerns of young people are the family and personal financial aspects. Areas affected by young people highlighted job stability, job opportunities, and are feared that school cycles will not be completed satisfactorily. Discussion or Conclusion: The main findings of this study are that the young population of the city seeks official information from the Ministry of Health through electronic means, as well as consuming information such as government conferences. In the health section, the youths have declared substantial changes in their physical and mental health, related to confinement and physical distance measures. In the education section, the participants mentioned a decrease interest in academic issues and a considerable increase in the academic load. In the employment section, the youths declared changes in the way of working, using digital tools, reducing time in the workplace. Finally, an increase in frequency and quantity consumed of alcohol, tobacco, coffee, and other psychotropic substances is declared, in addition to the time of browsing on social networks and the Internet.

COVID-19 and suicide: when crises collide.

Suicide is a leading cause of death worldwide. Even before the emergence of the novel coronavirus SARS-CoV2 COVID-19 pandemic, suicide continued to be a major public health concern. Globally, someone dies by suicide every 40 s, and for each death, there are 20 more persons attempting suicide. A recently published article rightly stated the need for a ‘population-based approach’ to suicide prevention to mitigate suicide attempts. This paper further adds that there must be a stronger multi-agency or multi-sectoral approach to suicide prevention, intervention and postvention. This paper concludes with few suggestions on how to address the COVID-19-related suicide cases as the world continues to fight against the double pandemic.

Identifying structural-functional analogue of GRL0617, the only well-established inhibitor for papain-like protease (PLpro) of SARS-CoV2 from the pool of fungal metabolites using docking and molecular dynamics simulation.

The non-structural protein (nsp)-3 of SARS-CoV2 coronavirus is sought to be an essential target protein which is also named as papain-like protease (PLpro). This protease cleaves the viral polyprotein, but importantly in human host it also removes ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from interferon responsive factor 3 (IRF3) protein which ultimately downregulates the production of type I interferon leading to weakening of immune response. GRL0617 is the most potent known inhibitor for PLpro that was initially developed for SARS outbreak of 2003. The PLpro of SARS-CoV and CoV2 share 83% sequence identity but interestingly have several identical conserved amino acids that suggests GRL0617 to be an effective inhibitor for PLpro of SARS-CoV2. GRL0617 is a naphthalene-based molecule and interacts with Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro). To identify PLpro inhibitors, we prepared a library of secondary metabolites from fungi with aromatic nature and docked them with PLpro of SARS-CoV and SARS-CoV2. We found six hits which interacts with Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro). More surprisingly the top hit, Fonsecin, has naphthalene moiety in its structure, which recruits Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro) and has binding energy at par with control (GRL0617). Molecular dynamics (MD) simulation showed Fonsecin to interact with Tyr268 of SARS-CoV2-PLpro more efficiently than control (GRL0617) and interacting with a greater number of amino acids in the binding cleft of PLpro.Graphic abstract

Corona citizens' science project-repeated surveys of the Irish response to COVID-19 and subsequent lockdown and restrictive measures.

BackgroundWorldwide, many people have been affected by COVID-19, a novel respiratory illness, caused by a new type of coronavirus SARS-CoV2. The COVID-19 outbreak is considered a pandemic and has created a number of challenges for the general population, patients, and healthcare professionals. Lockdowns have been implemented to slow down the spread of the virus with the expectation that these restrictions will limit the number of cases, and hence the number of hospitalizations and ICU admissions. However, these restrictions, and in particular lockdowns, impact on the life of everyone living in Ireland.AimTo record how the COVID-19 pandemic and subsequent restrictive measures impacted on people’s activities, work, schooling, and childcare.MethodsThe Corona Citizens’ Science Project was set up as a population-wide survey. A questionnaire was designed, and the survey was first launched on the 8th of April 2020. An overview of results was released in the press days later. Data was collected in four waves: April 8, April 22, May 6, and June 17, 2020. Each wave had core questions allowing to compare each wave, and wave-specific questions, to understand current impact of changing measures.ResultsOver four waves, 152,259 responses were collected. The mean age of respondents was 47 with about 10% over the age of 65. Around 75% were female and 85% had a higher degree.Nearly 70% of the respondents were in employment, and around 13% were retired. Up to 20% of the respondents were essential workers, and 10% of respondents indicated they were in receipt of the COVID-19 pandemic unemployment payment.Around 10% of the people who responded were living alone. The number of people talked to the previous day was on average 2.3 in the first survey; during the lockdown, this went up over time, and in the last survey, the mean was 3.9. The percentage of respondents who did not talk to anyone the previous day decreased from 40 to 22% over the waves.In the first wave, about 6% of respondents reported having had flu-like symptoms in the last 14 days, which declined to 3.3%, 2.5%, and 2.0% in waves 2, 3, and 4 respectively. Similarly, over the four waves, the respondents who indicated that someone they lived with had flu-like symptoms declined from 17 to 12%, 9%, and 11%. Throughout the four waves, nearly one third of people reported one or more underlying conditions.ConclusionsAs a result of the COVID-19 pandemic, a number of restrictive measures, in particular lockdown, were implemented in Ireland to protect populations and healthcare systems. To record some of the major impacts on society, we launched a Corona Citizens Science Project, with the aim to support decision-making. This report provides detail of its findings.