Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of RdRp from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), provided the first ever insights into the domain organisation and possible functional characteristics of the NiRAN domain. Using in silico tools, we predict that the NiRAN domain assumes a kinase or phosphotransferase like fold and binds nucleoside triphosphates at its proposed active site. Additionally, using molecular docking we have predicted the binding of three widely used kinase inhibitors and five well characterized anti-microbial compounds at the NiRAN domain active site along with their drug-likeliness as well as DFT properties. For the first time ever, using basic biochemical tools, this study shows the presence of a kinase like activity exhibited by the SARS-CoV-2 RdRp. Interestingly, the proposed kinase inhibitors and a few of the predicted nucleotidyl transferase inhibitors significantly inhibited the aforementioned enzymatic activity. In line with the current global COVID-19 pandemic urgency and the emergence of newer strains with significantly higher infectivity, this study provides a new anti-SARS-CoV-2 drug target and potential lead compounds for drug repurposing against SARS-CoV-2.

With the development of social media, the information about vector-borne disease incidence over broad spatial scales can cause demand for local vector control before local risk exists. Anticipatory intervention may still benefit local disease control efforts; however, infection risks are not the only focal concerns governing public demand for vector control. Concern for environmental contamination from pesticides and economic limitations on the frequency and magnitude of control measures also play key roles. Further, public concern may be focused more on ecological factors (i.e., controlling mosquito populations) or on epidemiological factors (i.e., controlling infection-carrying mosquitoes), which may lead to very different control outcomes. Here we introduced a generic Ross-MacDonald model, incorporating these factors under three spatial scales of disease information: local, regional, and global. We tailored and parameterized the model for Zika virus transmitted by Aedes aegypti mosquito. We found that overreaction caused by larger-scale incidence information could decrease average human infections per patch breeding capacity, however, the associated increase in total control effort plays a larger role, which leads to an overall decrease in control efficacy. The shift of focal concerns from epidemiological to ecological risk could relax the negative effect of overreaction on control efficacy when mosquito breeding capacity populations are expected to be large. This work demonstrates that, depending on expected total mosquito breeding capacity population size, and weights of different focal concerns, large-scale disease information can reduce disease infections without lowering control efficacy. Our findings provide guidance for vector-control strategies by considering public reaction through social media.

Current RNA vaccines against SARS-CoV-2 are limited by instability of both the RNA and the lipid nanoparticle delivery system, requiring storage at −20°C or −70°C and compromising universally accessible vaccine distribution. This study demonstrates the thermostability and adaptability of a nanostructured lipid carrier (NLC) RNA vaccine delivery system for use in pandemic preparedness and pandemic response. Liquid NLC is stable at refrigerated temperatures for ≥ 1 year, enabling stockpiling and rapid deployment by point-of-care mixing with any vaccine RNA. Alternatively, NLC complexed with RNA may be readily lyophilized and stored at room temperature for ≥ 8 months or refrigerated temperature for ≥ 21 months. This thermostable RNA vaccine platform could significantly improve distribution of current and future pandemic response vaccines, particularly in low-resource settings. One Sentence Summary An RNA vaccine delivery system stable at room temperature for 8+ months and refrigerated for 21+ months.

Development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are urgently needed to combat the coronavirus disease 2019 (COVID-19). Oxysterols, defined as oxidized derivatives of cholesterol, include endogenous (naturally occurring) cholesterol metabolites as well as semi-synthetic oxysterol derivatives. We have previously studied the use of semi-synthetic oxysterol derivatives as drug candidates for inhibition of cancer, fibrosis, and bone regeneration. In this study, we have screened a panel of naturally occurring and semi-synthetic oxysterol derivatives for anti-SARS-CoV-2 activity, using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22( R )-hydroxycholesterol, 24( S )-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy186 displayed antiviral activity comparable to natural oxysterols. In addition, related oxysterol analogues Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fall into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell culture infection assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 with disrupting the formation of double membrane vesicles (DMVs), intracellular membrane compartments associated with viral replication. Oxy210 also inhibited the replication of hepatitis C virus, another RNA virus whose replication is associated with DMVs, but not the replication of the DMV-independent hepatitis D virus. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk developing COVID-19.

The SARS-CoV-2 pandemic triggered substantial economic and social disruptions. Mitigation policies varied across countries based on resources, political conditions, and human behavior. In the absence of widespread vaccination able to induce herd immunity, strategies to coexist with the virus while minimizing risks of surges are paramount, which should work in parallel with reopening societies. To support these strategies, we present a predictive control system coupled with a nonlinear model able to optimize the level of policies to stop epidemic growth. We applied this system to study the unfolding of COVID-19 in Bahia, Brazil, also assessing the effects of varying population compliance. We show the importance of finely tuning the levels of enforced measures to achieve SARS-CoV-2 containment, with periodic interventions emerging as an optimal control strategy in the long-term. One-sentence summary We present an adaptive predictive control algorithm to provide optimal public health measures to slow the COVID-19 transmission rate.

ABSTRACT Dysregulated inflammation dominated by chemokine expression is a key feature of disease following infection with the globally important human pathogens, Zika virus (ZIKV) and dengue virus, but a mechanistic understanding of how pro-inflammatory responses are initiated is lacking. Mitophagy is a quality control mechanism that regulates innate immune signaling and cytokine production through selective degradation of damaged mitochondria. Here, we demonstrate that ZIKV NS5 antagonizes mitophagy by binding to the host protein Ajuba and preventing its translocation to depolarized mitochondria where it is required for PINK1 activation and downstream signaling. Consequent mitophagy suppression amplified the production of pro-inflammatory chemokines through PKR sensing of mitochondrial RNA. In Ajuba −/− mice, ZIKV induced early expression of pro-inflammatory chemokines associated with significantly enhanced dissemination to tissues. This work identifies Ajuba as a critical regulator of mitophagy, and demonstrates a role for mitophagy in limiting systemic inflammation following infection by globally important human viruses.

The aim of the study is to analyze viruses using parameters obtained from distributions of nucleotide sequences in the viral RNA. Seeking for the input data homogeneity, we analyze single-stranded RNA viruses only. Two approaches are used to obtain the nucleotide sequences; In the first one, chunks of equal length (four nucleotides) are considered. In the second approach, the whole RNA genome is divided into parts by adenine or the most frequent nucleotide as a "space''. Rank--frequency distributions are studied in both cases. The defined nucleotide sequences are signs comparable to a certain extent to syllables or words as seen from the nature of their rank--frequency distributions. Within the first approach, the P\'olya and the negative hypergeometric distribution yield the best fit. For the distributions obtained within the second approach, we have calculated a set of parameters, including entropy, mean sequence length, and its dispersion. The calculated parameters became the basis for the classification of viruses. We observed that proximity of viruses on planes spanned on various pairs of parameters corresponds to related species. In certain cases, such a proximity is observed for unrelated species as well calling thus for the expansion of the set of parameters used in the classification. We also observed that the fourth most frequent nucleotide sequences obtained within the second approach are of different nature in case of human coronaviruses (different nucleotides for MERS, SARS-CoV, and SARS-CoV-2 versus identical nucleotides for four other coronaviruses). We expect that our findings will be useful as a supplementary tool in the classification of diseases caused by RNA viruses with respect to severity and contagiousness.

Background: Detection of SARS-CoV-2 antibodies among people at risk is critical for understanding both the prior transmission of COVID-19 and vulnerability of the population to the continuing transmission and, when done serially, the intensity of ongoing transmission over an interval in a community. In this study, we estimated the seroprevalence of COVID-19 in a representative population-based cohort of Iquitos, one of the regions with the highest mortality rates from COVID-19 in Peru, where a devastating number of cases occurred in March 2020. Methods: We conducted a population-based study of transmission tested each participant using the COVID-19 IgG/IgM Rapid Test from Orient Gene Biotech and used survey analysis methods to estimate seroprevalence accounting for the sampling design effect and test performance characteristics. Here we report results from the baseline (13 to 18 July 2020) and the first month of follow-up (13 to 18 August 2020) study. Findings: We enrolled a total of 716 participants and estimated seroprevalence of 70.0% (95% CI: 67.0%–73.4%), a test-re-test positivity of 65% (95% CI: 61.0%–68.3%), and an incidence of new exposures of 1.8% (95% CI: 0.9%–3.2%) data that suggest that transmission is ongoing but is occurring at low levels. We observed significant differences in the seroprevalence between age groups, with participants 18 to 29 years of age having lower seroprevalence than children <12 years of age (Prevalence ratio =0.85 [PR]; 95% CI: 0.73 – 0.98), suggesting that children were not refractory to infection in this setting. Interpretation: Iquitos demonstrates one of the highest rates of seroprevalence of COVID-19 worldwide. Current data shows a limited case burden in Iquitos for the past seven months and suggests that these levels are sufficient to provide significant but incomplete herd immunity. Funding Statement: Dirección Regional de Salud de Loreto, DIRESA, Loreto, Peru Declaration of Interests: We declare no conflict of interest. Ethics Approval Statement: The study was approved by the hospital health network Institutional Scientific Committee and Institutional Review Board of the Regional Hospital, Iquitos.

ABSTRACT Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations remain unknown. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate high Gas6 levels in the serum of patients with neurological complications which correlated with downregulation of genes associated with the type I IFN responses as consequence of Socs1 upregulation. Gas6 gamma-carboxylation is essential for ZIKV replication in monocytes, the main source of this protein. Gas6 also facilitates ZIKV replication in adult immunocompetent mice enabled susceptibility to transplacental infection and congenital malformations. Our data thus indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

ABSTRACT We use MD simulations to study the pore translocation properties of a pseudoknotted viral RNA. We consider the 71-nucleotide long xrRNA from Zika virus and establish how it responds when driven through a narrow pore by static or periodic forces applied to either one of the two termini. Unlike the case of fluctuating homopolymers, the onset of translocation is significantly delayed with respect to the application of static driving forces. Because of the peculiar xrRNA architecture, activation times can differ by orders of magnitude at the two ends. Instead, translocation duration is much smaller than activation times and occurs on timescales comparable at the two ends. Periodic forces amplify significantly the differences at the two ends, both for activation times and translocation duration. Finally, we use a waiting-times analysis to examine the systematic slowing-downs in xrRNA translocations and associate them to the hindrance of specific secondary and tertiary elements of xrRNA. The findings ought to be useful as a reference to interpret and design future theoretical and experimental studies of RNA translocation.

ABSTRACT Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

ABSTRACT We report Accurate SARS-CoV-2 genome Reconstruction (ACoRE), an amplicon-based viral genome sequencing workflow for the complete and accurate reconstruction of SARS-CoV-2 sequences from clinical samples, including suboptimal ones that would usually be excluded even if unique and irreplaceable. We demonstrated the utility of the approach by achieving complete genome reconstruction and the identification of false-positive variants in >170 clinical samples, thus avoiding the generation of inaccurate and/or incomplete sequences. Most importantly, ACoRE was crucial to identify the correct viral strain responsible of a relapse case, that would be otherwise mis-classified as a re-infection due to missing or incorrect variant identification by a standard workflow.

Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro . Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset (∼13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500μg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-γ levels.

With the rise of COVID-19 cases globally, many countries released digital tools to mitigate the effects of the pandemic. In Germany the Robert Koch Institute (RKI) published the Corona-Data-Donation-App, a virtual citizen science (VCS) project, to establish an early warning system for the prediction of potential COVID-19 hotspots using data from wearable devices. While work on motivation for VCS projects in HCI often presents egoistic motives as prevailing, there is little research on such motives in crises situations. In this paper, we explore the socio-psychological processes and motivations to share personal data during a pandemic. Our findings indicate that collective motives dominated among app reviews (n=464) and in in-depth interviews (n=10). We contribute implications for future VCS tools in times of crises that highlight the importance of communication, transparency and responsibility.

COVID-19 is caused by a newly identified coronavirus, SARS-CoV-2, and has become a pandemic around the world. The illustration of the immune responses against SARS-CoV-2 is urgently needed for understanding the pathogenesis of the disease and its vaccine development. CD8+ T cells are critical for virus clearance and induce long lasting protection in the host. Here we identified specific HLA-A2 restricted T cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides (n-Sp1, 2, 6, 7, 11, 13, 14) were confirmed to bind with HLA-A2 and potentially be presented by antigen presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. In addition, these epitopes could activate and generate epitope-specific T cells in vitro , and those activated T cells showed cytotoxicity to target cells. Meanwhile, all these epitopes exhibited high frequency of variations. Among them, n-Sp1 epitope variation 5L>F significantly decreased the proportion of specific T cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A2 and decreased the proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SAR-CoV-2.

Background: Zika virus (ZIKV) is a mosquito-borne disease discovered in 1947, but with no reports of serious disease for almost 60 years. The first large ZIKV outbreak was reported from Yap island in 2007, then in 2015, the emergence of ZIKV in the Americas highlighted clinical manifestations such as microcephaly and Guillain‐Barré syndrome. On February 1, 2016, WHO declared a Public Health Emergency of International Concern due to the magnitude of the outbreak, which then officially ended in November 2016. Methods: Ever since the Brazilian authority released the first report of autochthonous transmission of ZIKV in 2015, it became the object of interdisciplinary investigation and global research collaboration. To follow and understand the trend of ZIKV research, we performed a systematic review and meta-analysis of ZIKV publications during 2014-2018, by using the scientific database Scopus. Results: We found that the number of ZIKV related publications increased in 2016, 2017, and 2018 (39.2, 56.5, and 58.5 times, respectively) compared to an average number of publications (23.5) in 2014-2015. During the five years, there was not only an increment of publication numbers but also the area of research was expanded. In 2014-2015, the majority in the research area was epidemiological research with the aims to report the consequence of the ZIKV outbreak, and the trend was shifted to the development of diagnostic methods, antiviral treatment, and vaccine in the following three years. In addition, the number of countries involved in ZIKV research increased from 11 and 13 in 2014-2015 to 59, 67, and 66 in 2016-2018, showing that ZIKV research was changed from a low-level stage to active and globalized in the coming five years. Conclusions: Our results highlight the importance of gathering public interest when the world is facing the phase of global health alert, and how it can drive the research field from inactive to active. However, despite this enormous progress in ongoing ZIKV research, many questions are yet to be answered and should be addressed to accelerate the development of effective ZIKV countermeasures. Nevertheless, our systematic review and meta-analysis emphasized the importance of a worldwide multidisciplinary effort to combat outbreaks or unknown infectious disease threats in the future.

Introduction Coronavirus disease 2019 (COVID-19) has caused an unprecedented health crisis around the world, not least because of its heterogeneous clinical presentation and course. The new information on the pandemic emerging daily has made it challenging for healthcare workers (HCWs) to stay current with the latest knowledge, which could influence their attitudes and practices during patient care. Methods This study is a follow-up evaluation of changes in HCWs’ knowledge, attitudes, and practices as well as anxiety levels regarding COVID-19 since the beginning of the pandemic. Data were collected through an anonymous, predesigned, self-administered questionnaire that was sent online to HCWs in Saudi Arabia. Results The questionnaire was sent to 1500 HCWs, with a 63.8% response rate (N=957). The majority of respondents were female (83%), and the most common age group was 31–40 years (52.2%). Nurses constituted 86.3% of the respondents. HCWs reported higher anxiety during the COVID-19 pandemic which increased from 4.91±2.84 to 8.6±2.27 on an 11-point Likert scale compared to other viral outbreaks. HCWs believed that their own preparedness as well as that of their hospital’s intensive care unit (ICU) or emergency room (ER) was higher during the COVID-19 pandemic than during the Middle East respiratory syndrome coronavirus pandemic (2012–2015). About 58% of HCWs attended one or more simulations concerning the management of COVID-19 patients in their ICU/ER, and nearly all had undergone N95 mask fit testing. The mean score of HCWs’ knowledge of COVID-19 was 9.89/12. For most respondents (94.6%), the perception of being at increased risk of infection was the main cause of anxiety related to COVID-19; the mean score of anxiety over COVID-19 increased from 4.91±2.84 before to 8.6±2.27 during the pandemic in Saudi Arabia. Conclusions HCWs’ anxiety levels regarding COVID-19 have increased since a pandemic was declared. It is vital that healthcare facilities provide more emotional and psychological support for all HCWs.

ABSTRACT The biosafety level-3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research and countermeasure development. Here we report a trans -complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans -complementation system consists of two components: a genomic viral RNA containing a deletion of ORF3 and envelope gene, and a producer cell line expressing the two deleted genes. Trans- complementation of the two components generates virions that can infect naive cells for only one round, but does not produce wild-type SARS-CoV-2. Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. The results suggest that the trans -complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the spread and evolution of the virus across different populations, geographical regions and species. Here, we present a streamlined workflow—COVseq—based on the CUTseq method that we previously described, which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms, from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We validated COVseq on RNA extracted from the supernatant of a SARS-CoV-2 culture as well as from 85 RNA samples from nasopharyngeal swabs, demonstrating the ability of COVseq to achieve near complete genome coverage, including the S region encoding the spike protein. A cost analysis showed that COVseq could be used to sequence thousands of samples per week at less than 10 USD per sample, including library preparation and sequencing costs. COVseq is a versatile and scalable method that can be readily applied for genomic surveillance of the ongoing pandemic and easily adapted to other pathogens such as influenza viruses.

Scholars argue that the ‘‘science of science’’ studies have to investigate the critical role of exogenous events in the emergence of new research fields. The goal of this study is to analyze and explain the birth and growth of new research fields driven by exogenous event to science, such as COVID-19 (Coronavirus disease 2019) global pandemic crisis. This study here analyzes how the novel research field of COVID-19 emerges, in a comparative analysis with other scientific fields concerning respiratory illnesses (e.g., Chronic Obstructive Pulmonary Disease, COPD and Lung Cancer), to explain factors determining the unique dynamics of science that is generating scientific breakthroughs in a short period of time. The origin and evolution of the research field of COVID-19 reveal that has an acceleration of scientific production equal to a growth of 1.71% daily in 2020, laying the foundations for science advances and a likely paradigm shift in the treatment of infectious diseases with novel mRNA vaccines. Main results are generalized in properties that clarify the dynamics of science and explain the characteristics that generate the origin and evolution of new research fields driven by unforeseen crises with critical implications for technological and social change directed scientific progress of human societies.

Background: Zika virus (ZIKV) infection caused outbreak in Brazil, in 2015 and 2016. Disorganized urban growth, facilitates the concentration of numerous susceptible and infected individuals. It is useful to understand the mechanisms that can favor the increase in ZIKV incidence, such as areas with wide socioeconomic and environmental diversity. Therefore, the study analyzed the spatial distribution of ZIKV in the city of Rio de Janeiro, Brazil, in 2015 and 2016, and associations between the incidence per 1,000 inhabitants and socio-environmental factors. Methods: The census tracts were used as the analytical units reported ZIKV cases among the city’s inhabitants. Local Empirical Bayesian method was used to control the incidence rates’ instability effect. The spatial autocorrelation was verified with Moran’s Index and local indicators of spatial association (LISA). Spearman correlation matrix was used to indicate possible collinearity. The Ordinary Least Squares (OLS), Spatial Lag Model (SAR), and Spatial Error Model (CAR) were used to analyze the relationship between ZIKV and socio-environmental factors. Results: The SAR model exhibited the best parameters: R 2 = 0.44, Log-likelihood= -7482, Akaike Information Criterion (AIC) = 14980. In this model, mean income between 1 and 2 minimum wages was possible risk factors for Zika occurrence in the localities. Household conditions related to adequate water supply and the existence of public sewage disposal were associated with lower ZIKV incidence rates, suggesting possible protective factors against the occurrence of ZIKV in the localities. The presence of the Family Health Strategy in the census tracts was positively associated with the ZIKV incidence rate. However, the results show that mean income less than 1 minimum wage were negatively associated with higher ZIKV incidence rates. Discussion: The results demonstrate the importance of socio-environmental variables in the dynamics of ZIKV transmission and the relevance for the development of control strategies.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus, SARS-CoV-2, that appeared in late 2019 generating a high number of deaths and socioeconomic issues in human society. One of the fundamental questions in social studies of science is to analyze the evolution of new research fields during environmental threats, such as COVID-19 global pandemic crisis. This study analyzes the emergence and evolution of the research field of COVID-19 compared to other scientific fields concerning respiratory disorders, such as Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer, to explain the dynamics of science that is generating scientific breakthroughs in a short period of time. This study shows that the scientific production of the research field of COVID-19 has increased from January 2020 with an unparalleled velocity generating manifold scientific advances, discoveries and innovative drugs for a paradigm shift in the treatment of infectious diseases with mRNA vaccines. In particular, results reveal that acceleration of science in the research field of COVID-19, measured with scientific production, is equal to a growth of 1.71% daily, which is a level much higher than evolution of a normal research field that has a growth of scientific production of about 0.5% daily (e.g., COPD and Lung Cancer). These findings are generalized in properties of the dynamics of science to explain the characteristics of science that generate scientific breakthrough in the presence of environmental threats. Overall, then, this study clarifies, as far as possible, some novel characteristics of the origin of new research fields, crisis-driven, that support discoveries and innovations for guiding scientific and technological progress in society.

A significant subset of patients infected by SARS-CoV-2 presents olfactory, taste, and/or chemesthesis (OTC) disorders (OTCD). These patients recover rapidly, eliminating damage of sensory nerves. Discovering that S protein contains two ankyrin repeat binding motifs (S-ARBMs) and some TRP cation channels, implicated in OTC, have ankyrin repeat domains (TRPs-ARDs), I hypothesized that interaction of S-ARBMs and TRPs-ARDs could dysregulate the function of the latter and thus explains OTCD. Of note, some TRPs-ARDs are expressed in the olfactory epithelium, taste buds, trigeminal neurons in the oronasal cavity and vagal neurons in the trachea/lungs. Furthermore, this hypothesis is supported by studies that have shown: (i) respiratory viruses interact with TRPA1 and TRPV1 on sensory nerves and epithelial cells in the airways, (ii) the respiratory pathophysiology in COVID-19 patients is similar to lungs injuries produced by the sensitization of TRPV1 and TRPV4, and (iii) resolvin D1 and D2 shown to reduce SARS-CoV-2-induced inflammation, directly inhibit TRPA1, TRPV1, TRPV3 and TRPV4. Herein, results of blind dockings of S-ARBMs, 408-RQIAPG-413 (in RBD but distal from the ACE-2 binding region) and 905-RFNGIG-910 (in HR1), into TRPA1, TRPV1 and TRPV4 suggest that S-ARBMs interact with ankyrin repeat 6 of TRPA1 near an active site, and ankyrin repeat 3-4 of TRPV1 near cysteine 258 supposed to be implicated in the formation of inter-subunits disulfide bond. These findings suggest that S-ARBMs affect TRPA1, TRPV1 and TRPV4 function by interfering with channel assembly and trafficking. After an experimental confirmation of these interactions, among possible preventive treatments against COVID-19, the use of pharmacological manipulation (probably inhibition) of TRPs-ARDs to control or mitigate sustained pro-inflammatory response.

The SARS-CoV-2 coronavirus, which causes the COVID-19 pandemic, is one of the largest positive strand RNA viruses. Here we developed a simplified SPLASH assay and comprehensively mapped the in vivo RNA-RNA interactome of SARS-CoV-2 RNA during the viral life cycle. We observed canonical and alternative structures including 3’ -UTR and 5’ -UTR, frameshifting element (FSE) pseudoknot and genome cyclization in cells and in virions. We provide direct evidence of interactions between Transcription Regulating Sequences (TRS-L and TRS-Bs), which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE, forming a “high-order pseudoknot” embedding FSE, which might help ribosome stalling at frameshift sites. More importantly, we found that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome cyclization is weakened and genome domains remain stable. Our data provides a structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, describes dynamics of RNA structures during life cycle of SARS-CoV-2, and will help to develop antiviral strategies.