Background: The SARS-CoV-2 (COVID-19) pandemic has put the health care system under severe strain. Sexual and reproductive health services, including contraception provision, were one of the most disrupted. Our objective was to assess the impact of the COVID-19 pandemic on the sales of modern contraceptive methods in Brazil. Methods: We analysed monthly data of short-acting, long-acting reversible contraceptives (LARCs; implants and intrauterine devices [IUD]), and COVID-19 related deaths. We categorised the sales in: i) emergency contraceptive (EC), ii) oral contraceptives, rings and patches, iii) injectable contraceptives, iv) LARC methods, including copper-IUD, and v) LARC methods, except Cu-IUDs. Findings: Contraceptives sales had a non-significant increase in the year 2020 compared to the year 2019, and the annual average ranged from 12·8 to 13·0 million units/month. We observed an increase in the sales of injectable contraceptives for the February-May/2020 and EC pills for the June-July/2020 and a non-significant variation for pills, patches and rings. The hormonal-IUD/ENG-implant had three patterns: a decrease in sales between February-April, which coincides with the closure of family planning services; an increment of sales since April, which coincide with the first COVID-19 related deaths and an important increment of sales since July/2020.Interpretation: The COVID-19 pandemic has disrupted the Brazilian healthcare system and due to the fact that many family planning clinics were closed, the sales of most of the modern contraceptives fall over the year 2020; however, the increment of sales of the LNG-IUD/ENG-implant at private sector indicated the inequity in access of contraception. Funding Information: This study received partial financial support from the Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP; award number 2015/20504‐9) and from the Brazilian National Research Council (CNPq; grant number 573747/2008‐3). Moreover, CMC and AM received funding from SRH, part of the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organisation (WHO), to complete their Post-graduate studies. This article represents the views of the named authors only and does not represent the views of the mentioned organisations. Declaration of Interests: LB received honoraria as lecturer from Bayer Healthcare and MSD. The other authors declared no conflict of interest.

Background SARS-Cov-2 is a new virus that caused an epidemic disease, COVID-19. According to the world health organization, detecting the patients/carriers is by the far the most important action to prevent the pandemic. Recently, the loop-mediated isothermal amplification (LAMP) technique has become more popular due to the easy handling of a one-step kit used for the detection of many diseases than RT-PCR-based techniques. methods Herein, we used the RT-LAMP technique so as to detect COVID-19. To this end, 40 paired-samples of patients and healthy people had been collected and tested by RT-PCR for N and E genes of SARS-CoV-2. The RT-LAMP test has been performed on samples for the RdRp gene. The sensitivity and specificity of tests have been determined. Results The testing results are consistent with the conventional RT-qPCR. Additionally, we also showed that a one-step process without RNA extraction is feasible to achieve RNA amplification directly from a sample. Conclusion We confirmed that RT-LAMP is a rapid, simple, and sensitive method that can be used as a large-screening method, particularly in regional hospitals with limited access to high-technologies.

We present an unofficial SARS-CoV-2 genomic surveillance report from Slovakia based on approximately 3500 samples sequenced between March 2020 and May 2021. Early samples show multiple independent imports of SARS-CoV-2 from other countries. In Fall 2020, three virus variants (B.1.160, B.1.1.170, B.1.258) dominated as the number of cases increased. In November 2020, B.1.1.7 (alpha) variant was introduced in Slovakia and quickly became the most prevalent variant in the country (> 75% of new cases by early February 2021 and > 95% in mid-March).

ABSTRACT Background Globally there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID 19). Repurposing existing medications may offer the best hope for treating COVID 19 patients to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase (DHODH) inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with Oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents. (13) The IONIC trial is a randomized control trial that will investigate whether time to clinical improvement in COVID 19 patients is improved following a 14 day course of IMU-838 + Oseltamivir versus Oseltamivir alone. Methods IONIC trial is an open label study in which participants will be randomised 1:1 in two parallel arms; the intervention arm (IMU-838 + Oseltamivir) and control arm (Oseltamivir only). The primary outcome is time-to-clinical improvement; defined as the time from randomisation to: a 2-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by UHCW NHS Trust and funded by LifeArc. Discussion The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [ IONIC Intervention ] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care. Trial Registration The trial was registered with EudraCT (2020-001805-21) on 09.04.2020 and ISRCTN on 23.09.2020 ( ISRCTN53038326 ) and Clinicaltrials.gov on 17.08.2020 ( NCT04516915 ) Strengths and Limitations This study is the first to recruit participants in the trial exploring the effectiveness of IMU-838 in COVID-19. In addition, we believe it is the only trial exploring the effectiveness of IMU-838 in combination with Oseltamivir (Tamiflu) in patients with moderate to severe COVID-19. However, to make the trial design flexible due to the on-going pandemic the trial is un-blinded.

Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiologic processes in humans, thus providing unique opportunities for discovery of host targeting antivirals. We interrogated the ReFRAME repurposing library with 12,993 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus, mapping to 59 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor and dopamine receptor and cyclin-dependent kinase inhibitors. Counter-screening with SARS-CoV-2 and validation in primary cells identified Phortress, an aryl hydrocarbon receptor (AHR) ligand, Bardoxolone and Omaveloxolone, two nuclear factor, erythroid 2 like 2 (NFE2L2) activators as inhibitors of both alpha- and betacoronaviruses. The landscape of coronavirus targeting molecules provides important information for the development of broad-spectrum antivirals reinforcing pandemic preparedness.

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

5-Methylcytosine (m 5 C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m 5 C methyltransferase, can negatively regulate type I interferon responses during viral infection. NSUN2 specifically mediates m 5 C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 could enhance type I interferon responses and downstream ISG expression after viral infection in vitro . And in vivo , the antiviral innate responses is more dramatically enhanced in Nsun2 +/− mice than in Nsun2 +/+ mice. Four highly m 5 C methylated cytosines in IRF3 mRNA were identified, and their mutation could enhance the cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), Zika virus (ZIKV), or especially SARS-CoV-2 resulted in a reduction in endogenous levels of NSUN2. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease after viral infection to boost antiviral responses for the effective elimination of viruses. Our results suggest a paradigm of innate antiviral immune responses ingeniously involving NSUN2-mediated m 5 C modification.

ABSTRACT Neuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection causes an extensive cell death and loss of post-synaptic termini. Despite limited neurotropism and a decelerating viral replication, we observe a threefold increase in microglial engulfment of postsynaptic termini after SARS-CoV-2 exposure. We define the microglial responses to SARS-CoV-2 infection by single cell transcriptomic profiling and observe an upregulation of interferon-responsive genes as well as genes promoting migration and synaptic stripping. To a large extent, SARS-CoV-2 exposed microglia display a transcriptomic profile previously observed in neurodegenerative disorders characterized by early a synapse loss and an increased incident risk after a Covid-19 infection. Our results reveal that brain organoids infected with SARS-CoV-2 display disruption in circuit integrity via microglia-mediated synapse elimination and identifies a potential novel mechanism contributing to cognitive impairments in patients recovering from Covid-19.

Despite the commonality of loss of lives, every pandemic has played a role in shaping the socio-economic and public health outcomes depending on the nature and the magnitude of the outbreak. In this study, we have attempted to make a preliminary assessment of COVID-19 impact on India and commented on the country’s resilience, response, impact and draw the lessons for the future. Although lockdown was necessary to stop the transmission, is showing and will show a greater impact on all spheres of human life considering the country’s poor resilient socio-economic institutions. Our concurrent assessment in the middle of the outbreak predicts that the socio-economic, demographic and health costs in India would be much higher than developed countries. Initiation of timely action from the very beginning (when the first case reported in Kerala) could have plummeted the potential transmission in every corner of the country to a large extent and could have avoided socio-economic crises that presently surfaced in the country. The study provides a strong message for initiating sector specific measures alongside relief packages to reduce the damage not only for now but also to build a resilient system for socioeconomically vulnerable groups, health care services, and education infrastructure to face future pandemics. Otherwise, the pandemic like this can cost more.

A year after the World Health Organisation (WHO) declared COVID-19 as a pandemic, much has been learned regarding SARS-CoV-2 epidemiology, vaccine production, and disease treatment. Whole-genome sequencing (WGS) has played a significant role in contributing to our understanding of the epidemiology and biology of this virus. In this paper, we investigate the use of SARS-CoV-2 WGS in Southeast and East Asia and the impact of technological development, access to resources, and demography of individual countries on its uptake. Using Oxford Nanopore Technology (ONT), Nottingham-Indonesia Collaboration for Clinical Research and Training (NICCRAT) initiative has facilitated collaboration between the University of Nottingham and a team in Research Centre for Biotechnology, Indonesian Institute of Sciences ( Lembaga Ilmu Pengetahuan Indonesia/LIPI ) to carry out a small number of SARS-CoV-2 WGS in Indonesia. The ONT offers sequencing advantages that fit within the Indonesian context. Analyses of SARS-CoV-2 genomes deposited on GISAID from Southeast and East Asian countries reveal the importance of collecting clinical and demographic metadata and the importance of open access and data sharing. Lineage and phylogenetic analyses per 1 June 2021 found that: 1) B.1.466.2 variants were the most predominant in Indonesia, with mutations in the spike protein including D614G at 100%, N439K at 99.1%, and P681R at 69.7% frequency, 2) The variants of concern (VoCs) B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) were first detected in Indonesia in January 2021, 3) B.1.470 was first detected in Indonesia and spread to the neighbouring regions, and 4) The highest rate of virus transmissions between Indonesia and the rest of the world appears to be through interactions with Singapore and Japan, two neighbouring countries with a high degree of access and travels to and from Indonesia.

Drug development for specific antiviral agents against coronavirus disease 2019 (COVID-19) is still an unmet medical need as the pandemic continues to spread globally. Although huge efforts for drug repurposing and compound screens have put forth, only few compounds remain in late stage clinical trials. New approaches and assays are needed to accelerate COVID-19 drug discovery and development. Here we report a time-resolved fluorescence resonance energy transfer-based assay that detects the severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) nucleocapsid protein (NP) produced in infected cells. It uses two specific anti-NP monoclonal antibodies (MAbs) conjugated to donor and acceptor fluorophores that produces a robust ratiometric signal for high throughput screening of large compound collections. Using this assay, we measured a half maximal inhibitory concentration (IC 50 ) for Remdesivir of 9.3 μM against infection with SARS-CoV-2 USA/WA1/2020 (WA-1). The assay also detected SARS-CoV-2 South African (Beta, β), Brazilian/Japanese variant P.1 (Gamma, γ), and Californian (Epsilon, ε), variants of concern or interest (VoC). Therefore, this homogeneous SARS-CoV-2 NP detection assay can be used for accelerating lead compound discovery for drug development and for evaluating drug efficacy against emerging SARS-CoV-2 VoC.

We are reporting a case of Guillain- Barré syndrome seven days after the first dose of Pfizer-BioNTech COVID-19 Vaccine. As this vaccine is still under investigation, reporting possible rare side effects is essential. In this case, the temporal relationship was suggestive of a vaccine-induced cause.

Since December 2019, the deadly novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 pandemic. To date, vaccines are available in the developed countries to prevent the infection of this virus, however, medicines are necessary to help control COVID-19. Human coronavirus 229E (HCoV-229E) causes the common cold. The main protease (M pro ) is an essential enzyme required for the multiplication of these two viruses in the host cells, and thus is an appropriate candidate to screen potential medicinal compounds. Flavonols and dihydroflavonols are two groups of plant flavonoids. In this study, we report docking simulation with two M pro enzymes and five flavonols and three dihydroflavonols, in vitro inhibition of the SARS-CoV-2 M pro , and in vitro inhibition of the HCoV 229E replication. The docking simulation results predicted that (+)-dihydrokaempferol, (+)-dihydroquercetin, (+)-dihydromyricetin, kaempferol, quercetin, myricentin, isoquercetin, and rutin could bind to at least two subsites (S1, S1’, S2, and S4) in the binding pocket and inhibit the activity of SARS-CoV-2 M pro . Their affinity scores ranged from −8.8 to −7.4. Likewise, these compounds were predicted to bind and inhibit the HCoV-229E M pro activity with affinity scores ranging from −7.1 to −7.8. In vitro inhibition assays showed that seven available compounds effectively inhibited the SARS-CoV-2 M pro activity and their IC50 values ranged from 0.125 to 12.9 µM. Five compounds inhibited the replication of HCoV-229E in Huh-7 cells. These findings indicate that these antioxidative flavonols and dihydroflavonols are promising candidates for curbing the two viruses.

Viruses can subvert a number of cellular processes in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection as well as datasets from the betacoronaviruses SARS-CoV and MERS as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV. We show that genes showing differential alternative splicing in SARS-CoV-2 have a similar functional profile to those of SARS-CoV and MERS and affect a diverse set of genes and biological functions, including many closely related to virus biology. Additionally, the differentially spliced transcripts of cells infected by coronaviruses were more likely to undergo intron-retention, contain a pseudouridine modification and a smaller number of exons than differentially spliced transcripts in the control groups. Viral load in clinical COVID-19 samples was correlated with isoform distribution of differentially spliced genes. A significantly higher number of ribosomal genes are affected by DAS and DGE in betacoronavirus samples, and the betacoronavirus differentially spliced genes are depleted for binding sites of RNA-binding proteins. Our results demonstrate characteristic patterns of differential splicing in cells infected by SARS-CoV-2, SARS-CoV, and MERS, potentially modifying a broad range of cellular functions and affecting a diverse set of genes and biological functions.

The study describes a novel strategy to screen natural products (NPs) based on their structural similarities with chemical drugs and their use as first-line treatment to Covid-19 infection. In the present study, the in-house natural product libraries, consisting of a total of 26,311 structures, were screened against potential targets of 2019-nCoV/SARS-CoV-2 based on their structural similarities with the prescribed chemical drugs. The comparison was based on molecular properties, 2 and 3-dimensional structural similarities, activity cliffs, and core fragments of NPs with chemical drugs. The screened NPs were evaluated for their therapeutic effects based on predicted in-silico pharmacokinetic and pharmacodynamics properties, binding interactions with the appropriate targets, and structural stability of the bound complex. The study yielded NPs with significant structural similarities to synthetic drugs currently used to treat Covid-19 infections. The study proposes the selected NPs as Anti-retroviral protease inhibitors, RNA-dependent RNA polymerase inhibitors, and viral entry inhibitors.

Background Non-targeted whole genome sequencing is a powerful tool to comprehensively identify constituents of microbial communities in a sample. There is no need to direct the analysis to any identification before sequencing which can decrease the introduction of bias and false negatives results. It also allows the assessment of genetic aberrations in the genome (e.g., single nucleotide variants, deletions, insertions and copy number variants) including in noncoding protein regions. Methods The performance of four different random priming amplification methods to recover RNA viral genetic material of SARS-CoV-2 were compared in this study. In method 1 (H-P) the reverse transcriptase (RT) step was performed with random hexamers whereas in methods 2-4 RT incorporating an octamer primer with a known tag. In methods 1 and 2 (K-P) sequencing was applied on material derived from the RT-PCR step, whereas in methods 3 (SISPA) and 4 (S-P) an additional amplification was incorporated before sequencing. Results The SISPA method was the most effective and efficient method for non-targeted/random priming whole genome sequencing of COVID that we tested. The SISPA method described in this study allowed for whole genome assembly of SARS-CoV-2 and influenza A(H1N1)pdm09 in mixed samples. We determined the limit of detection and characterization of SARS-CoV-2 virus which was 10 3 pfu/ml (Ct, 22.4) for whole genome assembly and 10 1 pfu/ml (Ct, 30) for metagenomics detection. Conclusions The SISPA method is predominantly useful for obtaining genome sequences from RNA viruses or investigating complex clinical samples as no prior sequence information is needed. It might be applied to monitor genomic virus changes, virus evolution and can be used for fast metagenomics detection or to assess the general picture of different pathogens within the sample.

ABSTRACT The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. Non-classical monocytes are capable of causing inflammation throughout the body in response to fractalkine/CX3CL1 and RANTES/CCR5.

Lab on a chip (LOC) device intakes fluid and makes it flow through the microchannels, to achieve rapid, highly sensitive and low-cost analysis with significant yield. Graphene has vast potential to be used in LOC devices owing to its remarkable and unique properties. A trustworthy, swift, inexpensive and facile detection scheme is of urgency due to the current situation of COVID-19 to break the chain of transmission and lab-on-chip based biosensor has materialized itself as a realistic solution for this purpose. The addition of Graphene has augmented the sensing capability of the LOC devices to a superior level. Recently, Graphene-based lab-on-chip type biosensor is effectively used for faithful detection of SARS-CoV-2 and this draws the attention of the researchers to review the recent progress in Graphene-based LOC platforms for detection of viruses and the same has been reviewed here.

Factors related to increasing globalization and climate change have contributed to the simultaneous increase and spread of arboviral diseases. Co-circulation of multiple arboviruses in the same geographic regions provides impetus to study the impacts of multiple arbovirus infections in a single vector. In the present study we describe co-infection and super-infection with Mayaro virus (Family Togaviridae, genus Alphavirus ) and Zika virus (family Flaviviridae, genus Flavivirus ) in vertebrate cells, mosquito cells, and Aedes aegypti mosquitoes to understand the interaction dynamics of these pathogens and effects on viral infection, dissemination and transmission. In Aedes aegypti mosquitoes, co-infection has a negative impact on infection and dissemination rates for Zika virus, but not Mayaro virus, when compared to single infection scenarios, and super-infection of Mayaro virus with a previous Zika virus infection resulted in increased Mayaro virus infection rates. We found that co-infection and super-infection negatively affected Zika viral replication in vertebrate cells (Vero and Huh), resulting in the complete blockage of Zika virus replication in some scenarios. At the cellular level, we demonstrate that single vertebrate and insect cells can be simultaneously infected with Zika and Mayaro viruses. This study highlights the dynamics of arboviral co- and super-infections and emphasizes the importance of considering these dynamics during risk assessment in epidemic areas.

Alphaviruses and flaviviruses have class II fusion glycoproteins that are essential for virion assembly and infectivity. Importantly, the tip of domain II is structurally conserved between the alphavirus and flavivirus fusion proteins, yet whether these structural similarities between virus families translate to functional similarities is unclear. Using in vivo evolution of Zika virus (ZIKV), we identified several novel emerging variants including an envelope glycoprotein variant in β-strand c (V114M) of domain II. We have previously shown that the analogous β-strand c and the ij loop, located in the tip of domain II of the alphavirus E1 glycoprotein, are important for infectivity. This led us to hypothesize that flavivirus E β-strand c also contributes to flavivirus infection. We generated this ZIKV glycoprotein variant and found that while it had little impact on infection in mosquitoes, it reduced replication in human cells and mice, and increased virus sensitivity to ammonium chloride, as seen for alphaviruses. In light of these results and given our alphavirus ij loop studies, we mutated a conserved alanine at the tip of the flavivirus ij loop to valine to test its effect on ZIKV infectivity. Interestingly, this mutation inhibited infectious virion production of ZIKV and yellow fever virus, but not West Nile virus. Together, these studies show that structurally analogous residues in the alphavirus and flavivirus class II fusion proteins contribute to virus infection in vivo and highlight these shared domains as targets for broad-spectrum arbovirus therapies. Author Summary Arboviruses are a significant global public health threat, yet there are no antivirals targeting these viruses. This problem is in part due to our lack of knowledge on the molecular mechanisms involved in the arbovirus life cycle. In particular, virus entry and assembly are essential processes in the virus life cycle and steps that can be targeted for the development of antiviral therapies. Therefore, understanding common, fundamental mechanisms used by different arboviruses for entry and assembly is essential. In this study, we show that flavivirus and alphavirus residues located in structurally conserved and analogous regions of the class II fusion proteins contribute to common mechanisms of entry, dissemination, and infectious virion production. These studies highlight how class II fusion proteins function and provide novel targets for development of antivirals.

ABSTRACT Background Millions have been exposed to SARS-CoV-2, but the severity of resultant infections has varied among adults and children, with adults presenting more serious symptomatic cases. Children may possess an immunity that adults lack, possibly from childhood vaccinations. This retrospective study suggests immunization against the poliovirus may provide an immunity to SARS-CoV-2. Methods Publicly available data were analyzed for possible correlations between national median ages and epidemiological outbreak patterns across 100 countries. Sera from 204 adults and children, who were immunized with the poliovirus vaccine, were analyzed using an enzyme-linked immunosorbent assay. The effects of polio-immune serum on SARS-CoV-2-induced cytopathology in cell culture were then evaluated. Results Analyses of median population age demonstrated a positive correlation between median age and SARS-CoV-2 prevalence and death rates. Countries with effective poliovirus immunization protocols and younger populations have fewer and less pathogenic cases of COVID-19. Antibodies to poliovirus and SARS-CoV-2 were found in pediatric sera and in sera from adults recently immunized with polio. Western blot demonstrated antibodies recognized the RNA-dependent-RNA-polymerase (RdRp) of either virus. Sera from polio-immunized individuals inhibited SARS-CoV-2 infection of Vero cell cultures. These results suggest the anti-D3-pol-antibody, induced by poliovirus vaccination, may provide a similar degree of protection from SARS-CoV-2 to adults as to children. Conclusions Poliovirus vaccination induces an adaptive humoral immune response. Antibodies created by poliovirus vaccination bind the RdRp protein of both poliovirus and SARS-CoV-2, thereby preventing SARS-CoV-2 infection. These findings suggest proteins other than “spike” proteins may be suitable targets for immunity and vaccine development.

Possible mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy is still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Three perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded (two cases confirmed by PCR, the third one based on clinical findings). In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, or drug use during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants. Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as strongly support COVID19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412 Date of registration: November 18, 2020

Neurological manifestation and complications are common due to COVID-19. It affects higher functions, cranial nerves and the motor system. The authors report a case of GBS as an example of a success story in managing a complicated case of COVID-19 in an elderly male with signs of a poor prognosis.

The limitations of virus-specific antiviral drugs became apparent during the current COVID-19 pandemic. The search for broad range antiviral proteins of a new kind to answer current and future pandemics has become an even more pressing matter. Here, the author further describes the expected anti-SARS-CoV-2 mechanisms of a novel broad range antiviral chimeric protein constructed between ricin A chain and pokeweed antiviral proteins. The latest in protein-ligand docking software were used to determine binding affinity of RTA-PAPs to SARS-CoV-2 frameshift stimulation element and elucidate the preferential post-infection entry mechanisms of RTA-PAPs into virus infected cells over non-infected ones, by doing a comparative analysis between in vitro and in silico results on numerous viruses. The results obtained strongly suggest that the post-infection preferential entry of RTA-PAPs into infected cells is mediated by the presence of viroporins integrated into the host cell membrane. The discovery of this mechanism revealed RTA-PAPs, and proteins like them, to be a new class of broad range antivirals that target with high specificity viroporin producing viruses, and with gain of functions in antiviral activities, post-infection.

Background COVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. Methods Randomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Each group was composed of 25 mild, 25 moderate and 25 severe patients. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. Results NCS did not enhance survival rate as three of severe COVID-19 patients in NCS and in control groups died (P>0.05). However, NCS, compared to control group, reduced the time to recovery in moderate and severe COVID-19 patients about 5 and 3 days, respectively but not in mild patients (P≤0.05). Most interestingly, NCS lowered time to recovery up to five days in patients with co-morbidities (P≤0.05) whereas only one day lowered in patients without co-morbidities (P>0.05). Conclusion It is concluded that NCS accelerates time to recovery about 3 to 5 days in moderate to severe COVID-19 patients especially those with co-morbidities; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.