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chronic treatment with hydroxychloroquine and sars-cov-2 infection.hydroxychloroquine sulfate (hcq) is being scrutinized for repositioning in the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection. this antimalarial drug is also chronically used to treat patients with autoimmune diseases. by analyzing the portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving hcq for the management of diseases, such as systemic lupus erythematosus, rheumatoid ...202032644224
excavating sars-coronavirus 2 genome for epitope-based subunit vaccine synthesis using immunoinformatics approach.since the outbreak of severe acute respiratory syndrome-coronavirus 2 (sars-cov-2) in december 2019 in china, there has been an upsurge in the number of deaths and infected individuals throughout the world, thereby leading to the world health organization declaration of a pandemic. since no specific therapy is currently available for the same, the present study was aimed to explore the sars-cov-2 genome for the identification of immunogenic regions using immunoinformatics approach. a series of c ...202032643158
povidone-iodine demonstrates rapid in vitro virucidal activity against sars-cov-2, the virus causing covid-19 disease.as of 22 june 2020, severe acute respiratory syndrome (sars)-coronavirus (cov)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. the virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. we report the in vitro virucidal activity of topical and oral povidone-iodine (pvp-i) products against sars-cov-2.202032643111
development of a synthetic poxvirus-based sars-cov-2 vaccine.modified vaccinia ankara (mva) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. we developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant mva vectors from chemically synthesized dna. in response to the ongoing global pandemic caused by sars coronavirus-2 (sars-cov-2), we used this novel vaccine platform to rapidly produce fully synthetic mva (smva) vectors co-expressing sars-c ...202032637957
sars-cov-2 infection of primary human lung epithelium for covid-19 modeling and drug discovery.coronavirus disease 2019 (covid-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2). severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. we developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to sars-cov-2 infection. differentiated air-liquid inte ...202032637946
road toward rapid-molecular point of care test to detect novel sars-coronavirus 2019 (covid-19): review from updated literature.coronavirus disease 2019 (covid-19) named by the who as a result of the global public health emergency. covid-19 is caused by a new coronavirus named as novel coronavirus (2019-ncov). from the first case reported in december 2019 it is now a pandemic situation and a major public health emergency. the covid-19 transmission rate is very high, infecting two to three persons on average with contact to an already infected person. there is a need for the health system, specially in developing countrie ...202032636083
analysis of sars-cov-2 rna-dependent rna polymerase as a potential therapeutic drug target using a computational approach.the severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) outbreak originating in wuhan, china, has raised global health concerns and the pandemic has now been reported on all inhabited continents. hitherto, no antiviral drug is available to combat this viral outbreak.202032635935
cathepsin b protease facilitates chikungunya virus envelope protein-mediated infection via endocytosis or macropinocytosis.chikungunya virus (chikv) is an enveloped virus that enters host cells and transits within the endosomes before starting its replication cycle, the precise mechanism of which is yet to be elucidated. endocytosis and endosome acidification inhibitors inhibit infection by chikv, murine leukemia virus (mlv), or sars-coronavirus, indicating that these viral entries into host cells occur through endosomes and require endosome acidification. although endosomal cathepsin b protease is necessary for mlv ...202032635194
an update on the origin of sars-cov-2: despite closest identity, bat (ratg13) and pangolin derived coronaviruses varied in the critical binding site and o-linked glycan residues.the initial cases of severe acute respiratory syndrome coronavirus-2 (sars-cov-2) occurred in wuhan, china, in december 2019 and swept the world by 23 june 2020 with 8 993 659 active cases, 469 587 deaths across 216 countries, areas or territories. this strongly implies global transmission occurred before the lockdown of china. however, the initial source's transmission routes of sars-cov-2 remain obscure and controversial. research data suggest bat (ratg13) and pangolin carried cov were the pro ...202032633815
vimentin as a multifaceted player and potential therapeutic target in viral infections.vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. consequently, vimentin has complex implications in pathophysiology. vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, eithe ...202032630064
sars-cov-2 host diversity: an update of natural infections and experimental evidence.coronavirus disease-19 (covid-19) caused by the severe acute respiratory syndrome coronavirus-2 (sars-cov-2) is now a pandemic threat. this virus is supposed to be spread by human to human transmission. cellular angiotensin-converting enzyme 2 (ace2) is the receptor of sars-cov-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans. moreover, a recent study predicted that dogs might be secondary hosts during the evolution of s ...202032624360
shotgun proteomics analysis of sars-cov-2-infected cells and how it can optimize whole viral particle antigen production for vaccines.severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) has resulted in a pandemic and is continuing to spread rapidly around the globe. no effective vaccine is currently available to prevent covid-19, and intense efforts are being invested worldwide into vaccine development. in this context, all technology platforms must overcome several challenges resulting from the use of an incompletely characterized new virus. these include finding the right conditions for virus amplification f ...202032619390
challenges for management of immune thrombocytopenia during covid-19 pandemic. 202032619062
whole genome analysis and targeted drug discovery using computational methods and high throughput screening tools for emerged novel coronavirus (2019-ncov).a novel coronavirus designated as sars-cov-2 in february 2020 by world health organization (who) was identified as main cause of sars like pneumonia cases in wuhan city in hubei province of china at the end of 2019. this been recently declared as global pandemic by who. there is a global emergency to identify potential drugs to treat the sars-cov-2. currently, there is no specific treatment against the new virus. there is a urgency to identifying potential antiviral agents to combat the disease ...202032617527
primary exposure to sars-cov-2 protects against reinfection in rhesus macaques.coronavirus disease 2019 (covid-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), has become a global pandemic. it is unclear whether convalescing patients have a risk of reinfection. we generated a rhesus macaque model of sars-cov-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. rhesus macaques reinfected with the identical sars-cov-2 strain ...202032616673
gene signatures of sars-cov/sars-cov-2-infected ferret lungs in short- and long-term models.coronaviruses (covs) consist of six strains, and the severe acute respiratory syndrome coronavirus (sars-cov), newly found coronavirus (sars-cov-2) has rapidly spread leading to a global outbreak. the ferret (mustela putorius furo) serves as a useful animal model for studying sars-cov/sars-cov-2 infection and developing therapeutic strategies. a holistic approach for distinguishing differences in gene signatures during disease progression is lacking. the present study discovered gene expression ...202032615317
assessing the application of a pseudovirus system for emerging sars-cov-2 and re-emerging avian influenza virus h5 subtypes in vaccine development.highly pathogenic emerging and re-emerging viruses continuously threaten lives worldwide. in order to provide prophylactic prevention from the emerging and re-emerging viruses, vaccine is suggested as the most efficient way to prevent individuals from the threat of viral infection. nonetheless, the highly pathogenic viruses need to be handled in a high level of biosafety containment, which hinders vaccine development. to shorten the timeframe of vaccine development, the pseudovirus system has be ...202032611537
critical role of type iii interferon in controlling sars-cov-2 infection in human intestinal epithelial cells.severe acute respiratory syndrome-related coronavirus-2 (sars-cov-2) is an unprecedented worldwide health problem that requires concerted and global approaches to stop the coronavirus 2019 (covid-19) pandemic. although sars-cov-2 primarily targets lung epithelium cells, there is growing evidence that the intestinal epithelium is also infected. here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of the sars-cov-2 lif ...202032610043
hypercytokinemia and pathogen-host interaction in covid-19.severe acute respiratory syndrome (sars) coronavirus (cov)-2 (sars-cov-2) is a novel coronavirus identified as the cause of coronavirus disease-2019 (covid-19) that began in wuhan, china in late 2019 and spread now in 210 countries and territories around the world. many people are asymptomatic or with mild symptoms. however, in some cases (usually the elderly and those with comorbidities) the disease may progress to pneumonia, acute respiratory distress syndrome and multi-organ dysfunction that ...202032606886
childbirth, puerperium and abortion care protocol during the covid-19 pandemic.the new coronavirus (severe acute respiratory syndrome-related coronavirus 2, sars-cov-2) is a virus that causes a potentially serious respiratory disease that has spread in several countries, reaching humans in all age groups, including pregnant women. the purpose of this protocol is to provide technical and scientific support to brazilian obstetricians regarding childbirth, postpartum and abortion care during the pandemic.202032604438
sars-cov-2 pathophysiology and assessment of coronaviruses in cns diseases with a focus on therapeutic targets.the novel coronavirus disease of 2019 (ncov-19) is a viral outbreak noted first in wuhan, china. this disease is caused by severe acute respiratory syndrome (sars) coronavirus (cov)-2. in the past, other members of the coronavirus family, such as sars and middle east respiratory syndrome (mers), have made an impact in china and the arabian peninsula respectively. both sars and covid-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. ...202032603829
corticosteroid administration for viral pneumonia: covid-19 and beyond.corticosteroids are commonly used as adjuvant therapy for acute respiratory distress syndrome by many clinicians because of their perceived anti-inflammatory effects. however, for patients with severe viral pneumonia, the corticosteroid treatment is highly controversial.202032603802
structure-based screening of novel lichen compounds against sars coronavirus main protease (mpro) as potentials inhibitors of covid-19.the outbreak of sars-cov-2 and deaths caused by it all over the world have imposed great concern on the scientific community to develop potential drugs to combat coronavirus disease-19 (covid-19). in this regard, lichen metabolites may offer a vast reservoir for the discovery of antiviral drug candidates. therefore, to find novel compounds against covid-19, we created a library of 412 lichen compounds and subjected to virtual screening against the sars-cov-2 main protease (mpro). all the ligands ...202032602074
novel phosphatidylinositol 4-kinases iii beta (pi4kiiiβ) inhibitors discovered by virtual screening using free energy models.herein, the lassbio chemical library is presented as a valuable source of compounds for screening to identify hits suitable for subsequent hit-to-lead optimization stages. a feature of the lassbio chemical library worth highlighting is the fact that it is a smart library designed by medicinal chemists with pharmacological activity as the main priority. the great majority of the compounds part of this library have shown in vivo activity in animal models, which is an indication that they possess o ...202032601839
boning up: amino-bisphophonates as immunostimulants and endosomal disruptors of dendritic cell in sars-cov-2 infection.amino-bisphosphonates such as zoledronic acid (za) can possibly ameliorate or prevent severe covid-19 disease by at least three distinct mechanisms: (1) as immunostimulants which could boost γδ t cell expansion, important in the acute response in the lung; (2) as dc modulators, limiting their ability to only partially activate t cells; and (3) as prenylation inhibitors of small gtpases in the endosomal pathway of the dc to prevent expulsion of lysosomes containing sars-cov-2 virions. use of za o ...202032600410
[hypertension, raas blockade and risk in covid-19 patients].sars-coronavirus 2 (sars-cov-2) enters the host-cells by binding the transmembraneous angiotensin converting enzyme 2 (ace2) when causing coronavirus disease 2019 (covid-19). the role of angiotensin converting enzyme inhibitors (ace) and angiotensin ii receptor blockers (arb) in covid-19 is debated. several well-conducted observational studies show no increased risk from raas blockade in covid-19 patients and are detailed in this brief review. the swedish society of hypertension, stroke and vasc ...202032594472
covid-19 in immunocompromised hosts: what we know so far.the coronavirus disease 2019 (covid-19) pandemic caused by sars coronavirus 2 (sars-cov-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. the clinical features and outcomes of covid-19 among immunosuppressed patients, who are at presumed risk for more severe disease but who may also have decreased detrimental inflammatory responses, are not well characterized. we review the existing literature on covid-19 among immunocompromised populations ...202032592461
molecular evolution and phylogenetic analysis of sars-cov-2 and hosts ace2 protein suggest malayan pangolin as intermediary host.an emergence of a novel coronavirus, causative agent of covid19, named as severe acute respiratory syndrome coronavirus 2 (sars-cov-2), occurred due to cross-species transmission. coronaviruses are a large family of viruses able to infect a great number of hosts. entrance of sars-cov-2 depends on the surface (s) protein interaction with host ace2 protein and cleavage by tmprss2. ace2 could be a species-specific barrier that interferes with bat-to-human coronavirus cross-species transmission. mol ...202032592038
sars-cov-2 and hiv protease inhibitors: why lopinavir/ritonavir will not work for covid-19 infection.since the beginning of the outbreak of severe acute respiratory syndrome (sars) coronavirus (cov) 2 lopinavir/ritonavir was selected for treatment. the recent publication of cao et al in the nejm[1] showed that lopinavir/ritonavir treatment did not accelerate clinical improvement compared with standard of care. this raised the question if we in retrospect could have known this. the aim of this paper is to gather all the available evidence and to comprehensively discuss this issue.202032589165
the d614g mutation in the sars-cov-2 spike protein reduces s1 shedding and increases infectivity.sars coronavirus 2 (sars-cov-2) isolates encoding a d614g mutation in the viral spike (s) protein predominate over time in locales where it is found, implying that this change enhances viral transmission. we therefore compared the functional properties of the s proteins with aspartic acid (s d614 ) and glycine (s g614 ) at residue 614. we observed that retroviruses pseudotyped with s g614 infected ace2-expressing cells markedly more efficiently than those with s d614 . this greater infectivity w ...202032587973
does early childhood vaccination protect against covid-19?the coronavirus disease 2019 (covid-19) is an on-going pandemic caused by the sars-coronavirus-2 (sars-cov-2) which targets the respiratory system of humans. the published data show that children, unlike adults, are less susceptible to contracting the disease. this article aims at understanding why children constitute a minor group among hospitalized covid-19 patients. here, we hypothesize that the measles, mumps, and rubella (mmr) vaccine could provide a broad neutralizing antibody against numb ...202032582766
recent understandings toward coronavirus disease 2019 (covid-19): from bench to bedside.in late december 2019, an unprecedented outbreak of coronavirus disease 2019 (covid-19) caused by sars coronavirus 2 (sars-cov-2) (previously named 2019-ncov) in wuhan became the most challenging health emergency. since its rapid spread in china and many other countries, the world health organization (who) declared covid-19 a public health emergency of international concern (pheic) on 30th january 2020 and a pandemic on 11th march 2020. thousands of people have died, and there are currently no v ...202032582719
main clinical features of covid-19 and potential prognostic and therapeutic value of the microbiota in sars-cov-2 infections.coronavirus disease 2019 (covid-19), caused by severe acute respiratory syndrome (sars) coronavirus 2 (sars-cov-2), has become a pandemic, infecting more than 4,000,000 people worldwide. this review describes the main clinical features of covid-19 and potential role of microbiota in covid-19. sars-cov and sars-cov-2 have 79.5% nucleotide sequence identity and use angiotensin-converting enzyme 2 (ace2) receptors to enter host cells. the distribution of ace2 may determine how sars-cov-2 infects th ...202032582134
rampant c→u hypermutation in the genomes of sars-cov-2 and other coronaviruses: causes and consequences for their short- and long-term evolutionary trajectories.the pandemic of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. to understand the early evolutionary events following its emergence, a data set of 985 complete sars-cov-2 sequences was assembled. variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 × 10-4 substitutions/site/year. almost one-half of seq ...202032581081
report of positive placental swabs for sars-cov-2 in an asymptomatic pregnant woman with covid-19.currently, limited data on maternal and neonatal outcomes of pregnant women with infection and pneumonia related to sars coronavirus 2 (sars-cov-2) are available. our report aims to describe a case of placental swabs positive for the molecular research on severe acute respiratory syndrome coronavirus 2 (sars-cov-2 rna in an asymptomatic woman with positive rhino-pharyngeal swab for sars-cov-2 who underwent an urgent cesarean section in our obstetrics unit. sample collection, processing, and labo ...202032580461
could sars-cov-2 affect male fertility?we performed this systematic review to evaluate the possibility of an impact of sars-cov-2 infection on male fertility. sars-cov-2 enters the cells with the help of ace2; therefore, testicular expression of ace2 was analysed from transcriptome sequencing studies and our unpublished data. literature suggested that sars-cov-1 (2002-2004 sars) had a significant adverse impact on testicular architecture, suggesting a high possibility of the impact of sars-cov-2 as well. out of two studies on semen s ...202032578263
heterogeneous expression of the sars-coronavirus-2 receptor ace2 in the human respiratory tract.zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current covid-19 pandemic, caused by sars-cov-2. its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ace2 is a host ectopeptidase and the receptor for sars-cov-2. despite numerous reports describing ace2 mrna abundance and tissue distribution, there remains a paucity of data evaluating ace2 protein and its co ...202032577664
effective inhibition of sars-cov-2 entry by heparin and enoxaparin derivatives.severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. currently there is no vaccine, effective therapeutic or prophylactic. like other betacoronaviruses, attachment and entry of sars-cov-2 is mediated by the spike glycoprotein (sgp). in addition to its well-documented interaction with its receptor, human angiotensin converting enzyme 2 (hace2), sgp has been f ...202032577638
hiv and sars-coronavirus-2 epidemics: possible interactions and need for studies, especially in africa. 202032574323
conducting phase i trials during the sars-coronavirus-2 outbreak: about science and care. 202032574280
innate immune signaling and proteolytic pathways in the resolution or exacerbation of sars-cov-2 in covid-19: key therapeutic targets?covid-19 is caused by the severe acute respiratory syndrome (sars) coronavirus (cov)-2, an enveloped virus with a positive-polarity, single-stranded rna genome. the initial outbreak of the pandemic began in december 2019, and it is affecting the human health of the global community. in common with previous pandemics (influenza h1n1 and sars-cov) and the epidemics of middle east respiratory syndrome (mers)-cov, covs target bronchial and alveolar epithelial cells. virus protein ligands (e.g., haem ...202032574272
covid-19 and sars coronavirus 2: antibodies for the immediate rescue and recovery phase. 202032574267
structural basis of sars-cov-2- and sars-cov-receptor binding and small-molecule blockers as potential therapeutics.over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (sars-cov-2) 2019 pandemic, have majorly challenged public health. the path for virus invasion into humans and other hosts is mediated by host-pathogen interactions, specifically virus-receptor binding. an in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and small-molecule inhibitors that ...202032574109
syrian hamsters as a small animal model for sars-cov-2 infection and countermeasure development.at the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; sars-cov-2) was detected in wuhan, china, that spread rapidly around the world, with severe consequences for human health and the global economy. here, we assessed the replicative ability and pathogenesis of sars-cov-2 isolates in syrian hamsters. sars-cov-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection. in addition, microco ...202032571934
structural and functional conservation of the programmed -1 ribosomal frameshift signal of sars coronavirus 2 (sars-cov-2).approximately 17 years after the severe acute respiratory syndrome coronavirus (sars-cov) epidemic, the world is currently facing the covid-19 pandemic caused by sars corona virus 2 (sars-cov-2). according to the most optimistic projections, it will take more than a year to develop a vaccine, so the best short-term strategy may lie in identifying virus-specific targets for small molecule-based interventions. all coronaviruses utilize a molecular mechanism called programmed -1 ribosomal frameshif ...202032571880
chemical-informatics approach to covid-19 drug discovery: monte carlo based qsar, virtual screening and molecular docking study of some in-house molecules as papain-like protease (plpro) inhibitors.world health organization characterized novel coronavirus disease (covid-19), caused by severe acute respiratory syndrome (sars) coronavirus-2 (sars-cov-2) as world pandemic. this infection has been spreading alarmingly by causing huge social and economic disruption. in order to response quickly, the inhibitors already designed against different targets of previous human coronavirus infections will be a great starting point for anti-sars-cov-2 inhibitors. in this study, our approach integrates d ...202032568618
sars-coronavirus-2 replication in vero e6 cells: replication kinetics, rapid adaptation and cytopathology.the sudden emergence of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) at the end of 2019 from the chinese province of hubei and its subsequent pandemic spread highlight the importance of understanding the full molecular details of coronavirus infection and pathogenesis. here, we compared a variety of replication features of sars-cov-2 and sars-cov and analysed the cytopathology caused by the two closely related viruses in the commonly used vero e6 cell line. compared to sars-cov, ...202032568027
constituents of buriti oil (mauritia flexuosa l.) like inhibitors of the sars-coronavirus main peptidase: an investigation by docking and molecular dynamics.statistics show alarming numbers of infected and killed in the world, caused by the covid-19 pandemic, which still doesn't have a specific treatment and effective in combating all efforts to seek treatments and medications against this disease. natural products are of relevant interest in the search for new drugs. thus, buriti oil (mauritia flexuosa l.) is a natural product extracted from the fruit of the palm and is quite common in the legal amazon region, brazil. in the present work, the anti- ...202032567501
air microbiome and pollution: composition and potential effects on human health, including sars coronavirus infection.polluted air poses a significant threat to human health. exposure to particulate matter (pm) and harmful gases contributes to cardiovascular and respiratory diseases, including allergies and obstructive lung disease. air pollution may also be linked to cancer and reduced life expectancy. uptake of pm has been shown to cause pathological changes in the intestinal microbiota in mice and humans. less is known about the effects of pollution-associated microbiota on human health. several recent studi ...202032565838
sars-cov-2: diagnostic and design conundrums in the context of male factor infertility.the question of whether sars-cov-2 (severe acute respiratory syndrome-related coronavirus-2 [sars-cov-2], leading to the covid-19 infection) can be harboured in the testes and/or semen is currently unanswered. it is essential to understand the limitations of both antibody and real-time pcr tests in interpreting sars-cov-2 data in relation to analyses of semen and testicular tissue without appropriate controls. this article critically analyses the evidence so far on this, and the possible implica ...202032565229
sars-cov-2 coinfections: could influenza and the common cold be beneficial?the novel coronavirus severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has rapidly spread around the world, causing serious illness and death and creating a heavy burden on the healthcare systems of many countries. since the virus first emerged in late november 2019, its spread has coincided with peak circulation of several seasonal respiratory viruses, yet some studies have noted limited coinfections between sars-cov-2 and other viruses. we use a mathematical model of viral coinfect ...202032557776
convergent antibody responses to sars-cov-2 in convalescent individuals.during the coronavirus disease-2019 (covid-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (sars-cov-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. the entry of the virus into cells depends on the receptor-binding domain (rbd) of the spike (s) protein of sars-cov-2. although there is currently no vaccine, it is likely that antibodies will be essential for protection. however, little is known about the human antibody respons ...202032555388
effects of gene-eden-vir and novirin on sars-cov: implications for covid-19.the coronavirus (sars-cov-2), which causes covid-19, is a betacoronavirus closely related to the human severe acute respiratory syndrome (sars)-coronavirus (sars-cov). the recent covid-19 outbreak created an urgent need for treatment. to expedite the development of such treatment, pharmaceutical companies and government agencies are currently testing several existing drugs for their effect on the virus. gene-eden-vir and novirin are natural, broad-spectrum, antiviral treatments proven to be safe ...202032551855
coronavirus disease 2019: a new severe acute respiratory syndrome from wuhan in china.an outbreak of new severe acute respiratory syndrome coronavirus disease, coronavirus disease 2019 (covid-19), has emerged during december 2019. the ongoing outbreak in wuhan city spread rapidly throughout china, where the fatality rate ranged from 2.1 to 4.9%. due to its high transmissibility, the world health organization (who) declared a public health emergency of international concern on 30 january 2020. the current outbreak has the potential to become the first pandemic of the new millenniu ...202032551792
do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ace2) expression explain increased severity and mortality of covid-19 in males?coronavirus disease 2019 (covid-19), caused by severe acute respiratory syndrome (sars) coronavirus 2 (sars-cov-2), shares similarities with the former sars outbreak, which was caused by sars-cov-1. sars was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. covid-19 has a higher mortality rate in men both inside and outside china. in this opinion paper, we describe how sex-specific immunobiological factors and differences in ang ...202032549125
high-throughput interrogation of programmed ribosomal frameshifting in human cells.programmed ribosomal frameshifting (prf) is the controlled slippage of the translating ribosome to an alternative frame. this process is widely employed by human viruses such as hiv and sars coronavirus and is critical for their replication. here, we developed a high-throughput approach to assess the frameshifting potential of a sequence. we designed and tested >12,000 sequences based on 15 viral and human prf events, allowing us to systematically dissect the rules governing ribosomal frameshift ...202032546731
triage of critical care resources in covid-19: a stronger role for justice.some ethicists assert that there is a consensus that maximising medical outcomes takes precedence as a principle of resource allocation in emergency triage of absolutely scarce resources. but the nature of the current severe acute respiratory syndrome-related coronavirus 2 pandemic and the history of debate about balancing equity and efficiency in resource allocation do not support this assertion. i distinguish a number of concerns with justice and balancing considerations that should play a rol ...202032546657
an in silico approach for identification of novel inhibitors as potential therapeutics targeting covid-19 main protease.respiratory disease caused by a novel coronavirus, covid-19, has been labeled a pandemic by the world health organization. very little is known about the infection mechanism for this virus. more importantly, there are no drugs or vaccines that can cure or prevent a person from getting covid-19. in this study, the binding affinity of 2692 protease inhibitor compounds that are known in the protein data bank, are calculated against the main protease of the novel coronavirus with docking and molecul ...202032544024
evolutionary relationships and sequence-structure determinants in human sars coronavirus-2 spike proteins for host receptor recognition.coronavirus disease 2019 (covid-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (sars cov-2). the sars cov-2 is transmitted more rapidly and readily than sars cov. both, sars cov and sars cov-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ace-2) receptor. we generated multiple sequence alignments and phylogenetic trees for representative spike proteins of sars cov and sars cov-2 from various host s ...202032543705
development of an automatic integrated gene detection system for novel severe acute respiratory syndrome-related coronavirus (sars-cov2).in december 2019, wuhan, china suffered a serious outbreak of a novel coronavirus infectious disease (covid) caused by novel severe acute respiratory syndrome-related coronavirus (sars-cov 2). to quickly identify the pathogen, we designed and screened primer sets, and established a sensitive and specific qrt-pcr assay for sars-cov 2; the lower limit of detection (lod) was 14.8 (95% ci: 9.8-21) copies per reaction. we combined this qrt-pcr assay with an automatic integration system for nucleic ac ...202032543298
isolation of potent sars-cov-2 neutralizing antibodies and protection from disease in a small animal model.countermeasures to prevent and treat coronavirus disease 2019 (covid-19) are a global health priority. we enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (sars-cov-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. we isolated potent neutralizing antibodies (nabs) to two epitopes o ...202032540903
broad neutralization of sars-related viruses by human monoclonal antibodies.broadly protective vaccines against known and preemergent human coronaviruses (hcovs) are urgently needed. to gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory b cell repertoire of a convalescent severe acute respiratory syndrome (sars) donor and identified 200 sars coronavirus 2 (sars-cov-2) binding antibodies that target multiple conserved sites on the spike (s) protein. a large proportion of the non-neutralizing antibodies display high levels of somatic ...202032540900
a pathophysiological perspective on covid-19's lethal complication: from viremia to hypersensitivity pneumonitis-like immune dysregulation.severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the coronavirus responsible for our recent coronavirus disease 2019 pandemic, is driving a lung immunopathology that strongly resembles a severe form of hypersensitivity pneumonitis (hp). a review of recent severe acute respiratory syndrome-related coronavirus (sars-cov) and sars-cov-2 medical reports, as well as described characteristics of hp, lead us to postulate a theory for sars-cov-2 severe disease. we propose that the novel sar ...202032537960
a novel idea: the impact of serial interval on a modified-incidence decay and exponential adjustment (m-idea) model for projections of daily covid-19 cases.the sars-cov-2 virus causes the disease covid-19, and has caused high morbidity and mortality worldwide. empirical models are useful tools to predict future trends of disease progression such as covid-19 over the near-term. a modified incidence decay and exponential adjustment (m-idea) model was developed to predict the progression of infectious disease outbreaks. the modification allows for the production of precise daily estimates, which are critical during a pandemic of this scale for plannin ...202032537527
[comment] treatment strategies to fight the new coronavirus sars-cov-2: a challenge for a rubik's cube solver.sars-coronavirus-2 (sars-cov-2), the etiologic agent of the new lung disease covid-19 is closely related to sars-cov, and together with mers-cov are three new human coronaviruses that emerged in the last 20 years. the covid-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with sars and mers. clinical presentations range from asymptomatic or mild symptoms to severe illness. the prevalent cause of mortality is pneumonia that progresses to ards. the ...202032536988
a compendium answering 150 questions on covid-19 and sars-cov-2.in december 2019, china reported the first cases of the coronavirus disease 2019 (covid-19). this disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2), has developed into a pandemic. to date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. unequivocally, the covid-19 pandemic is the gravest health and socioeconomic crisis of our time. in this context, numerous questions have emerged in demand of basic scient ...202032535955
covid 19 diagnostic multiplicity and its role in community surveillance and control.diagnosis of persons exposed to/infected with severe acute respiratory syndrome-related coronavirus-2 (sars-cov-2) is central to controlling the global pandemic of covid-19. currently, several diagnostic modalities are available for covid-19, each with its own pros and cons. although there is a global consensus to increase the testing capacity, it is also essential to prudently utilize these tests to control the pandemic. in this paper, we have reviewed the current array of diagnostics for sars- ...202032532934
prospects of replication-deficient adenovirus based vaccine development against sars-cov-2.the current appearance of the new sars coronavirus 2 (sars-cov-2) and it quickly spreading across the world poses a global health emergency. the serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. nevertheless, currently there are no licensed vaccines for ...202032531955
endocrine changes in sars-cov-2 patients and lessons from sars-cov.coronavirus infection outbreaks have occurred frequently in the last two decades and have led to significant mortality. despite the focus on reducing mortality by preventing the spread of the virus, patients have died due to several other complications of the illness. the understanding of pathological mechanisms and their implications is continuously evolving. a number of symptoms occur in these patients due to the involvement of various endocrine glands. these clinical presentations went largel ...202032527756
ace2 and covid-19 and the resulting ards.this article reviews the correlation between ace2 and covid-19 and the resulting acute respiratory distress syndrome (ards). ace2 is a crucial component of the renin-angiotensin system (ras). the classical ace-angiotensin ⅱ (ang ii)-angiotensin type 1 receptor (at1r) axis and the ace2-ang(1-7)-mas counter-regulatory axis play an essential role in ras system. ace2 antagonises the activation of the classical ras ace-ang ii-at1r axis and protects against lung injury. similar to severe acute respira ...202032522846
immunoinformatics-guided designing of epitope-based subunit vaccines against the sars coronavirus-2 (sars-cov-2).sars coronavirus-2 (sars-cov-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. so far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. to date, no effective vaccine is available which can combat the infection caused by this virus. therefore, this study was conducted to design possible epitope-based subunit vaccines against the sars-cov-2 ...202032517882
clinical benefit of remdesivir in rhesus macaques infected with sars-cov-2.effective therapies to treat coronavirus disease 2019 (covid-19) are urgently needed. while many investigational, approved, and repurposed drugs have been suggested as potential treatments, preclinical data from animal models can guide the search for effective treatments by ruling out those that lack efficacy in vivo. remdesivir (gs-5734) is a nucleotide analogue prodrug with broad antiviral activity1,2 that is currently being investigated in covid-19 clinical trials and recently received emerge ...202032516797
the treatment of inflammatory bowel disease during the sars-cov-2 epidemic – practical advices: (a covid–19-pandémia orvosszakmai kérdései)patients with inflammatory bowel disease are more susceptible to severe viral infections requiring hospitalization regardless of treatment. immunosuppressives and biological treatments multiply the chances of opportunistic and lung infections, especially in combination therapy, so due to the new coronavirus (severe acute respiratory syndrome coronavirus-2) epidemic, which primarily causes respiratory disease, it is advisable to use different therapeutic considerations for effective and safe pati ...202032516119
glucovigilance in covid-19.the coronavirus disease (covid-19) pandemic has influenced clinical care in unprecedented ways. there is an urgent need to share best practice in providing diabetes care services in areas affected by covid. this is a brief review for clinicians managing diabetes in low-income countries based on currently available data. the data is rapidly evolving; however, people with diabetes and its related comorbidities have increased risk for severe disease, and prolonged recovery and mortality. this revie ...202032515386
reduced expression of covid-19 host receptor, ace2 is associated with small bowel inflammation, more severe disease, and response to anti-tnf therapy in crohn's disease.angiotensin-converting enzyme 2 ( ace2 ) has been identified as the host receptor for sars-coronavirus 2 (sars-cov-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths. utilizing transcriptomic data from four cohorts taken from crohn's disease (cd) and non-inflammatory bowel disease (ibd) subjects, we observed evidence of increased ace2 mrna in ileum with demographic features that have been associated with poor outcomes in covid-19 including age and raised ...202032511625
a multiscale and comparative model for receptor binding of 2019 novel coronavirus and the implication of its life cycle in host cells.the respiratory syndrome caused by a new type of coronavirus has been emerging from china and caused more than 1000 death globally since december 2019. this new virus, called 2019 novel coronavirus (2019-ncov) uses the same receptor called angiotensinconverting enzyme 2 (ace2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (sars) seventeen years ago. both viruses recognize ace2 through the spike proteins (s-protein) on their surfaces. it was found that the ...202032511419
sars-cov-2 spike protein binds heparan sulfate in a length- and sequence-dependent manner.severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. microarray binding experiments using an extensive heparan sulfate (hs) oligosaccharide library showed the spike of sars-cov-2 can bind hs in a length- and sequence-dependent manner. hexa- and octasaccharides composed of idoa2s-glcns6s repeating units were identified as optimal ligands. surface plasma resonance (spr) showed th ...202032511404
establishment of an african green monkey model for covid-19.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is responsible for an unprecedented global pandemic of covid-19. animal models are urgently needed to study the pathogenesis of covid-19 and to screen candidate vaccines and treatments. nonhuman primates (nhp) are considered the gold standard model for many infectious pathogens as they usually best reflect the human condition. here, we show that african green monkeys support a high level of sars-cov-2 replication and develop pronounced ...202032511377
an insertion unique to sars-cov-2 exhibits superantigenic character strengthened by recent mutations.multisystem inflammatory syndrome in children (mis-c) associated with coronavirus disease 2019 (covid-19) is a newly recognized condition in which children with recent sars-cov-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. these symptoms and the associated laboratory values strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic ...202032511374
a large-scale drug repositioning survey for sars-cov-2 antivirals.the emergence of novel sars coronavirus 2 (sars-cov-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (covid-19). to date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. as the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug reg ...202032511357
chadox1 ncov-19 vaccination prevents sars-cov-2 pneumonia in rhesus macaques.severe acute respiratory syndrome coronavirus-2 (sars-cov-2) emerged in december 20191,2 and is responsible for the covid-19 pandemic3. vaccines are an essential countermeasure urgently needed to control the pandemic4. here, we show that the adenovirus-vectored vaccine chadox1 ncov-19, encoding the spike protein of sars-cov-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. this response was not th2 dominated, as demonstrated by igg subclass and cytokine expression ...202032511340
characteristic and quantifiable covid-19-like abnormalities in ct- and pet/ct-imaged lungs of sars-cov-2-infected crab-eating macaques (macaca fascicularis).severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is causing an exponentially increasing number of coronavirus disease 19 (covid-19) cases globally. prioritization of medical countermeasures for evaluation in randomized clinical trials is critically hindered by the lack of covid-19 animal models that enable accurate, quantifiable, and reproducible measurement of covid-19 pulmonary disease free from observer bias. we first used serial computed tomography (ct) to demonstrate that bilate ...202032511338
the sequence of human ace2 is suboptimal for binding the s spike protein of sars coronavirus 2.the rapid and escalating spread of sars coronavirus 2 (sars-cov-2) poses an immediate public health emergency. the viral spike protein s binds ace2 on host cells to initiate molecular events that release the viral genome intracellularly. soluble ace2 inhibits entry of both sars and sars-2 coronaviruses by acting as a decoy for s binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. using deep mutagenesis, variants of ace2 are identified with increased bindin ...202032511321
editorial: diagnostic testing for sars-coronavirus-2 in the nursing facility: recommendations of a delphi panel of long-term care clinicians.with the covid-19 pandemic progressing, guidance on strategies to mitigate its devastating effects in nursing facilities (nfs) is critical to preventing additional tragic outcomes. asymptomatic spread of covid-19 from nursing facility staff and residents is a major accelerator of infection. facility-wide point-prevalence testing is an emerging strategy in disease mitigation. because time is not available to await the results of randomized controlled trials before implementing strategies in this ...202032510102
spiking pandemic potential: structural and immunological aspects of sars-cov-2.sars-coronavirus-2 (sars-cov-2) causes coronavirus disease 2019 (covid-19), an infectious respiratory disease causing thousands of deaths and overwhelming public health systems. the international spread of sars-cov-2 is associated with the ease of global travel, and societal dynamics, immunologic naiveté of the host population, and muted innate immune responses. based on these factors and the expanding geographic scale of the disease, the world health organization (who) declared the covid-19 out ...202032507543
routine antiemetic prophylaxis with dexamethasone during covid-19: should oncologists reconsider?the ongoing pandemic caused by severe acute respiratory syndrome (sars) coronavirus type 2 (sars-cov-2, also known as covid-19) has caused unprecedented strain on the global healthcare system, causing thousands of deaths worldwide. patients with underlying conditions such as cancer are at substantial risk of acquiring and dying from this novel coronavirus. numerous reports have shown that infection with sars-cov-2 causes depletion of b- and t-lymphocytes, including cd4 and cd8 t-cells, and is as ...202032507102
protective role of ace2 and its downregulation in sars-cov-2 infection leading to macrophage activation syndrome: therapeutic implications.in light of the outbreak of the 2019 novel coronavirus disease (covid-19), the international scientific community has joined forces to develop effective treatment strategies. the angiotensin-converting enzyme (ace) 2, is an essential receptor for cell fusion and engulfs the sars coronavirus infections. ace2 plays an important physiological role, practically in all the organs and systems. also, ace2 exerts protective functions in various models of pathologies with acute and chronic inflammation. ...202032504757
enhanced receptor binding of sars-cov-2 through networks of hydrogen-bonding and hydrophobic interactions.molecular dynamics and free energy simulations have been carried out to elucidate the structural origin of differential protein-protein interactions between the common receptor protein angiotensin converting enzyme 2 (ace2) and the receptor binding domains of the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) [a. e. gorbalenya et al., nat. microbiol. 5, 536-544 (2020)] that causes coronavirus disease 2019 (covid-19) [p. zhou et al., nature 579, 270-273 (2020)] and the sars coronavi ...202032503918
covid-19: the potential role of copper and n-acetylcysteine (nac) in a combination of candidate antiviral treatments against sars-cov-2.on march 11, 2020, the world health organization (who) declared the outbreak of coronavirus disease (covid-19) a pandemic. since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (sars-cov-2) more crucial than ever.202032503814
an off-the-shelf approach for the production of fc fusion proteins by protein trans-splicing towards generating a lectibody in vitro.monoclonal antibodies, engineered antibodies, and antibody fragments have become important biological therapeutic platforms. the igg format with bivalent binding sites has a modular structure with different biological roles, i.e., effector and binding functions, in different domains. we demonstrated the reconstruction of an igg-like domain structure in vitro by protein ligation using protein trans-splicing. we produced various binding domains to replace the binding domain of igg from escherichia ...202032503354
clinical features of familial clustering in patients infected with 2019 novel coronavirus in wuhan, china.an epidemic caused by sars-coronavirus-2 (sars-cov-2) infection has appeared in wuhan city in december 2019. the disease has shown a "clustering epidemic" pattern, and family-clustered onset has been the main characteristic. we collected data about 130 cases from 35 cluster-onset families (cofs) and 41 cases from 16 solitary-onset families (sofs). the incidence of 2019 coronavirus disease (covid-19) in cofs was significantly higher than that of sofs. our study also showed that patients with expo ...202032502551
covid-19 pandemic: a viewpoint from asia.the expansion of severe acute respiratory syndrome (sars) coronavirus 2 (sarscov-2) has now procured on epidemic percentages, affecting more than 190 nations in a matter of weeks. a widespread sarscov-2 contagion begun in wuhan, hubei province, china, and circulate through china and beyond in december 2019. the containment events in china have lessened new instances by more than 90%, but this diminution is not the case to a different place. european countries like italy and spain have been the m ...202032501384
sars-coronavirus-2 nsp13 possesses ntpase and rna helicase activities that can be inhibited by bismuth salts.the ongoing outbreak of coronavirus disease 2019 (covid-19) has become a global public health emergency. sars-coronavirus-2 (sars-cov-2), the causative pathogen of covid-19, is a positive-sense single-stranded rna virus belonging to the family coronaviridae. for rna viruses, virus-encoded rna helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral rnas. here, our studies show that sars-cov-2-encoded nonstruct ...202032500504
factors determining the diffusion of covid-19 and suggested strategy to prevent future accelerated viral infectivity similar to covid.this study has two goals. the first is to explain the geo-environmental determinants of the accelerated diffusion of covid-19 that is generating a high level of deaths. the second is to suggest a strategy to cope with future epidemic threats similar to covid-19 having an accelerated viral infectivity in society. using data on sample of n = 55 italian province capitals, and data of infected individuals at as of april 7th, 2020, results reveal that the accelerate and vast diffusion of covid-19 in ...202032498152
serodiagnostics for severe acute respiratory syndrome-related coronavirus 2 : a narrative review.accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. at the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement ...202032496919
angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with coronavirus disease 2019: friend or foe?when the coronavirus disease 2019 (covid-19) wreaked an unprecedented havoc of an escalating number of deaths and hospitalization in the united states, clinicians were faced with a myriad of unanswered questions, one of the them being the implication of the renin-angiotensin-aldosterone system in patients with covid-19. animal data and human studies have shown that angiotensin-converting enzyme (ace) inhibitors and angiotensin receptor blockers (arbs) increase the expression of ace2. ace2 is an ...202032496364
air pollution and covid-19: is the connect worth its weight?primary route of transmission of sars-cov-2 among humans is droplets and direct contact. airborne transmission of this virus is not established conclusively and so is the role of airborne particulate matter. this commentary examines the existing evidence about the role of particulate matter pollutants in sars-cov-2 transmission. pm2.5and other small particulate matter have been shown to carry viable virus particles in the air and incriminated in spread of measles and sars coronavirus. empirical ...202032496243
inflammasomes and pyroptosis as therapeutic targets for covid-19.the inflammatory response to severe acute respiratory syndrome-related coronavirus 2 infection has a direct impact on the clinical outcomes of coronavirus disease 2019 patients. of the many innate immune pathways that are engaged by severe acute respiratory syndrome-related coronavirus 2, we highlight the importance of the inflammasome pathway. we discuss available pharmaceutical agents that target a critical component of inflammasome activation, signaling leading to cellular pyroptosis, and the ...202032493814
retest positive for sars-cov-2 rna of "recovered" patients with covid-19: persistence, sampling issues, or re-infection?"retest positive" for severe acute respiratory syndrome-related coronavirus-2 (sars-cov-2) from "recovered" coronavirus disease-19 (covid-19) has been reported and raised several important questions for this novel coronavirus and covid-19 disease. in this commentary, we discussed several questions: (a) can sars-cov-2 re-infect the individuals who recovered from covid-19? this question is also associated with other questions: whether or not sars-cov-2 infection induces protective reaction or neut ...202032492212
retest positive for sars-cov-2 rna of "recovered" patients with covid-19: persistence, sampling issues, or re-infection?"retest positive" for severe acute respiratory syndrome-related coronavirus-2 (sars-cov-2) from "recovered" coronavirus disease-19 (covid-19) has been reported and raised several important questions for this novel coronavirus and covid-19 disease. in this commentary, we discussed several questions: (a) can sars-cov-2 re-infect the individuals who recovered from covid-19? this question is also associated with other questions: whether or not sars-cov-2 infection induces protective reaction or neut ...202032492212
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