Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.

Zika virus is a positive-sense single-stranded RNA virus, which can be transmitted across the placenta and leads to adverse effects on fetal development during pregnancy. The severity of these complications highlights the importance of prevention and treatment. However, no vaccines or drugs are currently available. In this study, we characterized the IFNβ-mediated antiviral response in trophoblast cells in order to identify critical components that are necessary for the successful control of viral replication; and determined whether we could use the components of the IFN-induced response as a replacement therapy for ZIKA viral infection during pregnancy. We identified and characterized interferon stimulated gene 20 (ISG20), playing a central role in controlling Zika infection in trophoblast cells, and successfully established a recombinant ISG20-Fc protein that effectively decrease viral titers in vitro and in vivo by maintaining its exonuclease activity and displaying immune modulatory functions. Therefore, rISG20-Fc is a promising anti-viral/immune modulatory approach for the control and prevention of RNA viral infections such as ZIKA virus.

Researchers worldwide are seeking to repurpose existing drugs or discover new drugs to counter the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A promising source of candidates for such studies is molecules that have been reported in the scientific literature to be drug-like in the context of coronavirus research. We report here on a project that leverages both human and artificial intelligence to detect references to drug-like molecules in free text. We engage non-expert humans to create a corpus of labeled text, use this labeled corpus to train a named entity recognition model, and employ the trained model to extract 10912 drug-like molecules from the COVID-19 Open Research Dataset Challenge (CORD-19) corpus of 198875 papers. Performance analyses show that our automated extraction model can achieve performance on par with that of non-expert humans.

Background: SARS-CoV-2 causes COVID-19 with a widely diverse disease profile that affect many different tissues. The mechanisms underlying its pathogenicity in host organisms remain unclear. Animal models for study the pathogenicity of SARS-CoV-2 proteins are lacking. Methods: : Using bioinformatic analysis, we showed that the majority of the virus-host interacting proteins are conserved in Drosophila . Therefore, we generated a series of transgenic lines for individual SARS-CoV-2 genes and used the Gal4-UAS system to express them in various tissues to study their pathogenicity. Results: : We found that the Nsp6, Orf6 and Orf7a transgenic flies displayed reduced trachea branching and muscle deficits resulting in “held-up” wing phenotype and poor climbing ability. Furthermore, muscle tissue in these flies showed dramatically reduced mitochondria. Since Orf6 was found to bind nucleopore proteins XPO1, we tested Selinexor, a drug that inhibits XPO1, and found that it could attenuated the Orf6-induced lethality and tissue-specific phenotypes in flies. Conclusions: : Our studies here established new Drosophila models for studying the function of SARS-CoV2 genes, identified Orf6 as a highly pathogenic protein in various tissues, and demonstrated the effects of Selinexor for inhibiting Orf6 toxicity with an in vivo model system.

This paper presents an analysis of the publication of datasets collected via Google Dataset Search, specialized in families of RNA viruses, whose terminology was obtained from the National Cancer Institute (NCI) thesaurus developed by the US Department of Health and Human Services. The objective is to determine the scope and reuse capacity of the available data, determine the number of datasets and their free access, the proportion in reusable download formats, the main providers, their publication chronology, and to verify their scientific provenance. On the other hand, we also define possible relationships between the publication of datasets and the main pandemics that have occurred during the last 10 years. The results obtained highlight that only 52% of the datasets are related to scientific research, while an even smaller fraction (15%) are reusable. There is also an upward trend in the publication of datasets, especially related to the impact of the main epidemics, as clearly confirmed for the Ebola virus, Zika, SARS-CoV, H1N1, H1N5, and especially the SARS-CoV-2 coronavirus. Finally, it is observed that the search engine has not yet implemented adequate methods for filtering and monitoring the datasets. These results reveal some of the difficulties facing open science in the dataset field.

The rapid growth of social media content during the current pandemic provides useful tools for disseminating information which has also become a root for misinformation. Therefore, there is an urgent need for fact-checking and effective techniques for detecting misinformation in social media. In this work, we study the misinformation in the Arabic content of Twitter. We construct a large Arabic dataset related to COVID-19 misinformation and gold-annotate the tweets into two categories: misinformation or not. Then, we apply eight different traditional and deep machine learning models, with different features including word embeddings and word frequency. The word embedding models (\textsc{FastText} and word2vec) exploit more than two million Arabic tweets related to COVID-19. Experiments show that optimizing the area under the curve (AUC) improves the models' performance and the Extreme Gradient Boosting (XGBoost) presents the highest accuracy in detecting COVID-19 misinformation online.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly transmitted by droplets and close contact, has caused a pandemic worldwide as of November 2020. According to the current case reports and cohort studies, the symptoms of pregnant women infected with SARS-CoV-2 were similar to normal adults and may cause a series of adverse consequences of pregnancy (placental abruption, fetal distress, epilepsy during pregnancy, etc.). However, whether SARS-CoV-2 can be transmitted to the fetus through the placental barrier is still a focus of debate. Methods In this study, in order to find out whether SARS-CoV-2 infect fetus through placental barrier, we performed qualitative detection of virus structural protein (spike protein and nucleoprotein) and targeted receptor protein (ACE2, CD147 and GRP78) expression on the placental tissue of seven pregnant women diagnosed with COVID-19 through immunohistochemistry. Amniotic fluid, neonatal throat, anal swab and breastmilk samples were collected immediately in the operating room for verification after delivery, which were all tested for SARS-CoV-2 by reverse transcriptionpolymerase chain reaction (RT-PCR). Results The result showed that CD147 was expressed on the basal side of the chorionic trophoblast cell membrane and ACE2 was expressed on the maternal side, while GRP78 was strongly expressed in the cell membrane and cytoplasm. The RT-PCR results of Amniotic fluid, neonatal throat, anal swab and breastmilk samples were all negative. Conclusions We believed that despite the detection of viral structural proteins in the placenta, SARS-CoV-2 cannot be transmitted to infants due to the presence of the placental barrier. Summary Our results showed that, excluding environmental pollution after birth and vaginal infection during childbirth, SARS-CoV-2 was less likely to be transmitted vertically in utero.

Understanding the evolutionary dynamics of the four human endemic coronaviruses might provide insight into the future trajectories of SARS-CoV-2 evolution. We re-assessed the timing of endemic coronavirus emergence and we show that all viruses entered human populations in a time-frame ranging from ~500 to 55 years ago. Because the three highly pathogenic coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) spilled-over in tight temporal succession, the pattern of coronavirus emergence, in analogy to that of influenza pandemics, is highly irregular. To contextualize this observation in a wider perspective of viral diseases emergence since 1945, we mined epidemiology database information. After controlling for reporting bias, we find that, contrary to widespread beliefs, the occurrence of viral diseases (either zoonotic or not) has not increased over the last decades. Analysis of the recent and ongoing evolution of HCoV-229E and HCoV-OC43 indicated that positive selection most likely contributed to fine-tune the interaction with the human interferon/inflammatory response. Conversely, integration of evolutionary inference and molecular dating provided evidence that these viruses are not undergoing antigenic drift and the temporal emergence of spike protein variants is best explained by optimization of receptor binding affinity. These data provide a fresh look on viral disease emergence and on coronavirus evolution.

All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predict small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of Cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV-1 and MERS-CoV. Indeed, two of these drugs- emetine and homoharringtonine- were independently shown to inhibit SARS-CoV-2 as this article was in preparation. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.

Background: In 2015-2017, the Americas experienced a highly consequential epidemics for pregnancy and childbearing. Mainly transmitted by the mosquito Aedes aegypti , but also through sexual intercourse, the Zika virus poses the risk of congenital Zika syndrome to fetus, which includes microcephaly and other child development complications. When a public health crisis taps directly into reproductive health, typically a feminine realm, responses to the emergency may exacerbate deeply-rooted gender norms. This paper investigates the role of gender in two relational contexts: a) the government-led response to the pandemic in terms of communication campaigns aimed at preventing Zika infections; and b) an individual level of response to the emergency, concerning women’s negotiation with their sexual partners with regard to the prevention of Zika as well as pregnancies. Methods: : We conducted content analysis of 94 unique pieces from public health communication campaigns produced by governmental agencies with the goal of promoting Zika awareness. Print and online materials were collected for one year (May 2016-May 2017), and included TV ads, Internet Pop-ups, and pamphlets. We also analyzed transcripts from 16 focus groups conducted with reproductive-aged women (18-40) in Belo Horizonte and Recife, two large cities differently affected by the Zika outbreak. Women answered open-ended questions connected to the epidemic, in areas such as personal knowledge and experiences with the Zika virus, experiences of their friends and acquaintances, their primary information sources, their perceptions of public health efforts toward containing the outbreak, as well as women’s contraceptive use. Results: : Campaign pieces handling pregnancy and microcephaly were largely gendered. Pieces targeted women, placing on their shoulders the responsibility for protecting a potential fetus from the disease. Importantly, campaigns neglected addressing male´s participation on Zika prevention and contraceptive management, while failing to take into account Brazil´s large proportion of unplanned pregnancies. Women were placed in a double bind by being expected to prevent both pregnancy and Zika, in a context where gendered power imbalances often translate in women having little power/means for condom negotiation /avoiding unprotected sexual intercourse. Conclusion: Government and individual responses to the epidemics reinforced gender roles, situating pregnant women as responsible for averting mosquito bites and microcephaly. Further, prevention campaigns largely excluded men. Since low-socioeconomic status women possessed fewer resources to preclude infection, we also found that beyond the gender divide, this subgroup faced more pronounced Zika prevention challenges as they found it harder to negotiate condom use with their sexual partners and often could not access other types of contraceptives resulting in unplanned pregnancies.

Background: The rapid expansion of dengue, Zika and chikungunya with large scale outbreaks are an increasing public health concern in many countries. Additionally, the recent coronavirus pandemic urged the need to get connected for fast information transfer and exchange. As response, health programmes have -among other interventions- incorporated digital tools such as mobile phones for supporting the control and prevention of infectious diseases. However, little is known about the benefits of mobile phone technology in terms of input, process and outcome dimensions. The purpose of this scoping review is to analyse the evidence of the use of mobile phones as an intervention tool regarding the performance, acceptance, usability, feasibility, cost and effectiveness in dengue, Zika and chikungunya control programmes. Methods: : We conducted a scoping review of studies and reports by systematically searching: i) electronic databases (PubMed, PLOS ONE, PLOS Neglected Tropical Disease, LILACS, WHOLIS, ScienceDirect and Google scholar), ii) grey literature, using Google web and iii) documents in the list of references of the selected papers. Selected studies were categorized using a pre-determined data extraction form. Finally, a narrative summary of the evidence related to general characteristics of available mobile health tools and outcomes was produced. Results: : The systematic literature search identified 1289 records, 32 of which met the inclusion criteria and 4 records from the reference lists. A total of 36 studies were included coming from twenty different countries. Five mobile phone services were identified in this review: mobile applications (n = 18), short message services (n=7), camera phone (n = 6), mobile phone tracking data (n = 4), and simple mobile communication (n = 1). Mobile phones were used for surveillance, prevention, diagnosis, and communication demonstrating good performance, acceptance and usability by users, as well as feasibility of mobile phone under real life conditions and effectiveness in terms of contributing to a reduction of vectors/ disease and improving users-oriented behaviour changes. It can be concluded that there are benefits for using mobile phones in the fight against arboviral diseases as well as other epidemic diseases. Further studies particularly on acceptance, cost and effectiveness at scale are recommended.

ABSTRACT Infectious diseases such as the COVID19 pandemic cemented the importance of disease tracking. The role of asymptomatic, undiagnosed individuals in driving infection has become evident. Their unaccountability results in ineffective prevention. We developed a pipeline using genomic data to accurately predict a population’s transmission network complete with the inference of unsampled sources. The system utilises Bayesian phylogenetics to capture evolutionary and infection dynamics of SARS-CoV-2. It identified the effectiveness of preventive measures in Canada’s Atlantic bubble and mobile populations such as New York State. Its robustness extends to the prediction of cross-species disease transmission as we inferred SARS-CoV-2 transmission from humans to lions and tigers in New York City’s Bronx Zoo. The proposed method’s ability to generate such complete transmission networks, provides a more detailed insight into the transmission dynamics within a population. This potential frontline tool will be of direct help in “the battle to bend the curve”.

During 2020, the infection rate of COVID-19 has been investigated by many scholars from different research fields. In this context, reliable and interpretable forecasts of disease incidents are a vital tool for policymakers to manage healthcare resources. Several experts have called for the necessity to account for human mobility to explain the spread of COVID-19. Existing approaches are often applying standard models of the respective research field. This habit, however, often comes along with certain restrictions. For instance, most statistical or epidemiological models cannot directly incorporate unstructured data sources, including relational data that may encode human mobility. In contrast, machine learning approaches may yield better predictions by exploiting these data structures, yet lack intuitive interpretability as they are often categorized as black-box models. We propose a trade-off between both research directions and present a multimodal learning approach that combines the advantages of statistical regression and machine learning models for predicting local COVID-19 cases in Germany. This novel approach enables the use of a richer collection of data types, including mobility flows and colocation probabilities, and yields the lowest MSE scores throughout our observational period in our benchmark study. The results corroborate the necessity of including mobility data and showcase the flexibility and interpretability of our approach.

Background: The COVID-19 pandemic has demonstrated the fragility of our healthcare systems and the need for rapid development of effective care strategies. Global efforts to develop novel therapeutics have intensified, but in late November 2020, few are approved. There is an urgent need for novel therapeutics to limit further spread of COVID-19. Passive immunity by infusing neutralising anti-SARS-CoV-2 antibodies provides a method to prevent infection in individuals at heightened risk such as frontline health care workers. Convalescent plasma (CP) collected from donors who have recovered from an infectious disease can be pooled and fractionated into hyperimmune intravenous immunoglobulin (HIVIG), a concentrated formulation with enriched levels of pathogen-specific antibodies. HIVIG are established for therapeutic and prophylactic administration across many infectious diseases and possess many advantages over CP including consistent high titres of antiviral antibodies without ABO matching or risk of transfusion related acute lung injury (TRALI) or transfusion associated circulatory overload (TACO), lower infusion volume, simpler storage, longer shelf life, and easier administration. Method: A parallel group, open-label, active control, phase 1/2 trial which allocates healthy adult healthcare workers never infected with SARS-CoV-2 to receive a single intravenous infusion of either CP or HIVIG. This clinical trial is the first to establish whether a HIVIG preparation concentrated with antibodies to SARS-CoV-2 is safe when administered to healthcare workers in the prevention of COVID-19, and to assess whether the anti-SARS-CoV-2 antibodies in the HIVIG are pharmacokinetically equivalent to those in unmodified CP. Discussion: Trials to date suggest that allocation of limited CP may be optimised if used for prevention rather than treatment of COVID-19. This HIVIG (Covimmune TM , Aegros Ltd.) is manufactured by a novel plasma fractionation technology (HaemaFrac TM , Aegros Ltd.) which offers high purity and a greater protein yield from smaller batches of starting plasma than is possible with conventional fractionation techniques. If successful, this approach can be rapidly scaled up for implementation into clinical practice and contribute to the sustainability of healthcare systems during the current and future pandemics. The more prevention and treatment options available to address the COVID-19 pandemic, the stronger the position our society will hold. Trial registration Australia & New Zealand Clinical Trials Registry. Registration number: ACTRN12620001249943p. Date: 20/11/2020. https://www.anzctr.org.au/ACTRN12620001249943p.aspx

Development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we found that mRNA-LNP immunization compared to protein immunization elicited either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope (prM-E) or HIV-1 Env gp160 induced durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 μg were immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.

The rapid outbreaks of lethal viruses necessitate the development of novel antiviral substance. Besides the conventional antiviral substances, biocompatible nanomaterials also have significant potential in combating the virus at various stages of infection. Carbon nanomaterials have an impressive record against viruses and can deal with many crucial healthcare issues. In accordance with the published literature, biocompatible carbon nanomaterials have a promising prospect as an antiviral substance. Subsequently, the antiviral properties of different carbon nanomaterials namely fullerene, carbon nanotube, carbon dot and graphene oxide have been reviewed.

The RNA pseudoknot that stimulates −1 programmed ribosomal frameshifting in SARS coronavirus-2 (SARS-CoV-2) is a possible drug target. To understand how this 3-stemmed pseudoknot responds to the mechanical tension applied by ribosomes during translation, which is thought to play a key role during frame-shifting, we probed its structural dynamics under tension using optical tweezers. Unfolding curves revealed that the frameshift signal formed multiple different structures: at least two distinct pseudoknotted conformers with different unfolding forces and energy barriers, as well as alternative stem-loop structures. Refolding curves showed that stem 1 formed first in the pseudoknotted conformers, followed by stem 3 and then stem 2. By extending the handle holding the RNA to occlude the 5′ end of stem 1, the proportion of the different pseudoknot conformers could be altered systematically, consistent with structures observed in cryo-EM images and computational simulations that had distinct topologies: the 5′ end of the RNA threaded through the 3-helix junction to form a ring-knot, or unthreaded as in more standard H-type pseudoknots. These results resolve the folding mechanism of the frameshift signal in SARS-CoV-2 and highlight the dynamic conformational heterogeneity of this RNA, with important implications for structure-based drug-discovery efforts.

COVID-19 breakout calls for immediate research explorations. The objective of this study is to perform a bibliometric analysis of all COVID-19-related publications in Science Citation Index Expanded (SCI-EXPANDED) in the early stage of the outbreak. Analysis parameters include performances of authors, institutes, and countries as well as distributions of Web of Science categories, journals, languages, and types of publications. Results show that 32% of total papers were published as editorial materials and an overwhelming production from Chinese research institutes. An association of research indexes with the number of cases was also found.

ABSTRACT The 2015/16 Zika virus epidemic in South and Central America left the scientific community urgently trying to understand the disease and the factors which modulate Zika virus pathogenesis. Multiple other flaviviruses are endemic in areas where Zika virus emerged in 2015/16. Therefore, it is hypothesized that a key to understanding how Zika virus infection and disease progresses, is to study Zika virus infection in the context of prior flavivirus exposure. Humans and animal studies have highlighted the idea that having been previously exposed to a heterologous flavivirus may modulate the immune response to Zika virus. However, it is still unclear 1) how this impacts viral burden and pathology, and 2) the factors which correlate with the multiple metrics of disease. In this murine study, we longitudinally examine multiple factors involved in Zika disease, linking viral burden over time with increased neurological disease severity and weight loss. We show that prior heterologous flavivirus exposure with dengue virus type 2 or 3, or the vaccine strain of yellow fever, provides protection from mortality in a lethal Zika challenge. Reduction in viral burden and Zika disease in the context of prior flavivirus exposure varies depending on the infecting primary virus; with primary Zika infection being most protective from Zika challenge, followed by dengue 2, yellow fever, and dengue 3. This study demonstrates a protective effect of prior heterologous flavivirus exposure on Zika virus pathogenesis, and defines the relationship between prior flavivirus exposure and the potential for Zika virus disease. IMPORTANCE The emergence and re-emergence of various vector-borne diseases in recent years highlights the need to understand the mechanisms of protection for each pathogen. In this study, we investigated the impact of prior exposure to Zika, dengue serotypes 2, 3, and the vaccine strain of yellow fever on pathogenesis and disease outcomes in a mouse model of Zika virus infection. We found that prior exposure to a heterologous flavivirus was protective from mortality, neurological disease, weight loss, and severe viral burden during a lethal Zika challenge. Using a longitudinal study design, we were able to link multiple disease parameters including viral burden over time with neurological disease severity and weight loss in the context of heterologous infection. This study demonstrates a role for heterologous flavivirus exposure in modulating flavivirus pathophysiology. Given the cyclic nature of most flavivirus outbreaks, this work will contribute to the forecasting of disease severity for future outbreaks.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and has infected an estimated 10% of the global population in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of a specific set of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.

Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders including Guillain-Barrè syndrome. A unique feature of flaviviruses is the secretion of non-structural protein 1 (NS1) by infected cells. NS1 is highly immunogenic and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. Of note, we demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which clones presenting cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV associated autoimmune manifestations.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new strain of coronavirus. There are three phases of COVID-19: early infection stage, pulmonary stage and hyper-inflammation stage respectively. It is important to prevent lung or other organs injuries by preventing phase-II and phase-III via pharmacological or non-pharmacological treatments. This was a case series study done on twenty-two patients confirmed to be infected with SARS-CoV-2 and diagnosed with COVID-19. Patients in this study have been used quercetin 800 mg, bromelain 165 mg, zinc acetate 50 mg and ascorbic acid 1 g once daily as supplements for 3 to 5 days during SARS-CoV-2 infection. The aim of this study is to evaluate the safety and efficacy of quercetin, bromelain, zinc and ascorbic acid combination supplements on patients with COVID-19. The mean levels of WBC, ANC, ALC, AMC and AST were normal among all included patients before and after taking quercetin, bromelain, zinc and ascorbic acid supplements (P-value > 0.05). Quercetin 800 mg, bromelain 165 mg, zinc acetate 50 mg and ascorbic acid 1 g once daily supplements were safe for patients infected with SARS-CoV-2 and may prevent poor prognosis. Randomized clinical trials needed in the future to ensure the efficacy of quercetin, bromelain, zinc and vitamin c combination.

An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to the global public health. Herbal medicines and their derived natural products have drawn much attention to treat COVID-19, but there has been no natural product showing inhibitory activity against SARS-CoV-2 infection with detailed mechanism. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection-routes via lysosome- and transmembrane protease, serine 2 (TMPRSS2)-driven entry. Mechanistically, PD prevents host-entry of SARS-CoV-2 by redistributing membrane cholesterol to prevent membrane fusion, which can be reinstated by treatment with a PD-encapsulating agent. Furthermore, the inhibitory effects of PD are recapitulated by a pharmacological inhibition or gene-silencing of NPC1 , which is mutated in Niemann-Pick type C (NPC) patients displaying disrupted membrane cholesterol. Finally, readily available local foods or herbal medicines containing PG root show the similar inhibitory effects against SARS-CoV-2 infection. Our study proposes that PD is a potent natural product for preventing or treating COVID-19 and that a brief disruption of membrane cholesterol can be a novel therapeutic approach against SARS-CoV-2 infection.

Consumer Behaviour is a complicated procedure. It relies upon a lot of elements that may incorporate the socio-political situation, monetary condition, and psychological profile of the purchaser. It, to a great extent, relies upon the buying intensity of the clients also. Presently from the earliest starting point of 2020, COVID-19 has affected all the business sectors all around on a scale which nobody could have anticipated, and in this way, the state of the economy has changed to such an extent that even financial experts do not have the option to accurately foresee the effect of this pandemic in the market situation. In this circumstance, the primary target of this study paper is to propose a few different ways the retail advertisers can take up after because of the impact of this frightening circumstance. To effectively anticipate and outline the connection between the customer conduct in Retail advertise, this paper has taken a generally littler market size and focused on just retail parts of Bihar state. The document has an accurate overview result, and it's an investigation that has been directed among different age gathering and individuals with the diverse socio-prudent foundation. In light of the study, the paper has spoken to an alert module that shows how the shopper conduct may move in post-COVID-19 and how it will affect the Retail advertise. As a feature of the paper, a proposed arrangement has been given, which shows a few measures to the retailers to follow to support the significant move and critical difference in customer conduct.

Zika virus (ZIKV), a mosquito-transmitted flavivirus, caused a large epidemic in Latin America between 2015 and 2017. Effective ZIKV vaccines and treatments are urgently needed to prevent future epidemics and severe disease sequelae. People infected with ZIKV develop strongly neutralizing antibodies linked to viral clearance and durable protective immunity. To understand mechanisms of protective immunity and to support the development of ZIKV vaccines, here we characterize the properties of a strongly neutralizing antibody, B11F, isolated from a recovered ZIKV patient. Our results indicate that B11F targets a complex epitope on the virus that spans domains I and III of the envelope glycoprotein. While previous studies point to quaternary epitopes centered on domain II of ZIKV E glycoprotein as targets of strongly neutralizing and protective human antibodies, we uncover a new site spanning domain I and III as a target of strongly neutralizing human antibodies. Importance People infected with Zika virus develop durable neutralizing antibodies that prevent repeat infections. In the current study, we characterize a ZIKV-neutralizing human monoclonal antibody isolated from a patient after recovery. Our studies establish a novel site on the viral envelope targeted by human neutralizing antibodies. Our results are relevant to understanding how antibodies block infection and for guiding the design and evaluation of candidate vaccines.