Antigen epitopes of animal coronaviruses:a mini-review

Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.

Stability and infectivity of coronaviruses in inanimate environments

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a highly contagious virus that can transmit through respiratory droplets,aerosols,or contacts.Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission.The inanimate surfaces have often been described as a source of nosocomial infections.However,summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present.This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces.The literature was systematically searched on Medline without language restrictions.All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included.Most viruses from the respiratory tract,such as coronaviruses,influenza,SARS-CoV,or rhinovirus,can persist on surfaces for a few days.Persistence time on inanimate surfaces varied from minutes to up to one month,depending on the environmental conditions.SARSCoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity.The most common coronaviruses may well survive or persist on surfaces for up to one month.Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature.Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection.The risk of transmission via touching contaminated paper is low.Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.

The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models

In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.

Coronaviruses and gastrointestinal diseases

The effects of coronaviruses on the respiratory system are of great concern,but their effects on the digestive system receive much less attention.Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting.Available data have shown that human coronaviruses,including the newly emerged SARS-CoV-2,mainly infect the respiratory system and cause symptoms such as cough and fever,while they may generate gastrointestinal symptoms.However,there is little about the relation between coronavirus and digestive system.This review specifically addresses the effects of mammalian and human coronaviruses,including SARS-CoV-2,on the digestive tract,helping to cope with the new virus infection-induced disease,COVID-19.

Digestive system involvement of infections with SARS-CoV-2 and other coronaviruses:Clinical manifestations and potential mechanisms

Although coronavirus(CoV)infection is often characterized by respiratory symptoms,the virus can also result in extrapulmonary symptoms,especially the symptoms related to the digestive system.The outbreak of coronavirus disease 2019(COVID-19)is currently the world’s most pressing public health threat and has a significant impact on civil societies and the global economy.The occurrence of digestive symptoms in patients with COVID-19 is closely related to the development and prognosis of the disease.Moreover,thus far,there are no specific antiviral drug or vaccine approved for the treatment or prevention of COVID-19.Therefore,we elaborate on the effects of CoVs on the digestive system and the potential underlying mechanisms.

Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2?

New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic(COVID-19)declared by WHO.Coronavirus disease 2019(COVID-19)is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2(SARS-CoV-2).SARS-CoV-2 is akin to SARS-CoV,which was the causative agent of severe acute respiratory syndrome(SARS)in 2002 as well as to that of Middle East respiratory syndrome(MERS)in 2012.SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member ofβ-coronaviruses.It has a positive-sense single-stranded RNA with the largest RNA genome.Since its genomic sequence has a notable similarity to that of SARS-CoV,antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment.In order to combat SARS-CoV-2,many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide.In this sense,medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses.In the present review,plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.

Multiple Sequence Alignment of the M Protein in SARS-Associated and Other Known Coronaviruses

In this paper, we report a multiple sequence alignment result on the basis of 10 amino acid sequences of the M protein, which come from different coronaviruses (4 SARS associated and 6 others known). The alignment model was based on the profile HMM (Hidden Markov Model), and the model training was implemented through the SAHMM (Self Adapting Hidden Markov Model) software developed by the authors.

The taxonomy, host range and pathogenicity of coronaviruses and other viruses in the Nidovirales order

The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some may occasionally cross the host barrier to infect livestock and even people,causing a variety of diseases.Since the beginning of the new century,increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics,including the recent COVID-19 pandemic.CoVs belong to the Coronaviridae family of the Nidovirales order.Recently,advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature.Here,we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range,genetic variation,genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses.This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses,including epidemic CoVs,which will benefit virological research and viral disease control.

Novel Coronaviruses and Astroviruses in Bats

Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses,which can be found from a wide range of mammals,were recently detected in bats. Strikingly,these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families,but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health.

Controversies’ clarification regarding ribavirin efficacy in measles and coronaviruses: Comprehensive therapeutic approach strictly tailored to COVID-19 disease stages

BACKGROUND Ribavirin is a broad-spectrum nucleoside antiviral drug with multimodal mechanisms of action,which supports its longevity and quality as a clinical resource.It has been widely administered for measles and coronavirus infections.Despite the large amount of data concerning the use of ribavirin alone or in combination for measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease 2019(COVID-19)outbreaks,the conclusions of these studies have been contradictory.Underlying reasons for these discrepancies include possible study design inaccuracies and failures and misinterpretations of data,and these potential confounds should be addressed.AIM To determine the confounding factors of ribavirin treatment studies and propose a therapeutic scheme for COVID-19.METHODS PubMed database was searched over a period of five decades utilizing the terms“ribavirin”alone or combined with other compounds in measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and COVID-19 infections.The literature search was performed and described according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Articles were considered eligible when they reported on ribavirin dose regimens and/or specified outcomes concerning its efficacy and/or possible adverseeffects.In vitro and animal studies were also retrieved.A chapter on ribavirin’s pharmacology was included as well.RESULTS In addition to the difficulties and pressures of an emerging pandemic,there is the burden of designing and conducting well-organized,double-blind,randomized controlled trials.Many studies have succumbed to specific pitfalls,one of which was identified in naturally ribavirin-resistant Vero cell lines in in vitro studies.Other pitfalls include study design inconsistent with the well-established clinical course of disease;inappropriate pharmacology of applied treatments;and the misinterpretation of study results with misconceived generalizations.A comprehensive treatment for COVID-19 is proposed,documented by thorough,longterm investigation of ribavirin regimens in coronavirus infections.CONCLUSION A comprehensive treatment strictly tailored to distinct disease stages was proposed based upon studies on ribavirin and coronavirus infections.

Diversity of coronaviruses in wild and domestic birds in Vietnam

Objective:To investigate the genetic diversity of coronaviruses in wild and domestic birds in the bird park and live poultry markets of Ca Mau province in Vietnam in 2020.Methods:A total of 228 samples(121 from wild birds and 107 from poultry)were collected in the territory of Ca Mau province of Vietnam in 2020.The avian samples were tested for the presence of the four genera of coronaviruses using reverse transcription and nested PCR.Molecular genetic analysis using targeted NGS sequencing of RdRp gene was performed for 29 representative samples(12 samples from wild birds and 17 from poultry).Phylogenetic analysis was performed using the neighbour joininig method with 1000 bootstrap replications using MEGA X software.Results:Among wild birds,21.5%samples were positive for the genetic material of coronaviruses and 38.3%samples were positive for coronaviruses among poultry.Genetic analysis of the partial sequence of RdRp gene from representative samples revealed that wild birds were carriers of gammacoronaviruses and deltacoronaviruses.Among poultry,three genotypes of infectious bronchitis virus(QX,Mass and Q1)were detected in chickens,with QX genotypes being predominant,and viruses of DCoV group were detected in domestic ducks.There was no detection of alphacoronaviruses or betacoronaviruses in the studied birds.Conclusions:Coronaviruses of genera Gammacoronavirus and Deltacoronavirus were detected in wild birds.A high percentage of infectious bronchitis virus was detected in poultry.Thus,there is a need for broader surveillance of coronaviruses in birds,which can be used for evaluation of diversity,evolution and distribution of coronaviruses in Vietnam.Continuous surveillance of coronaviruses circulation in wild and domestic animals is necessary for implementing strategic measures for poultry and domestic animal protection and for evaluation of possible risk of circulating coronaviruses to human health.

Coronaviruses:An overview with special emphasis on COVID-19 outbreak with musculoskeletal manifestations

An acute respiratory illness caused by a novel coronavirus,namely,severe acute respiratory syndrome coronavirus 2,the virus that causes coro-navirus disease 2019(COVID-19),began spreading across China in late December 2019.The disease gained global attention as it spread worldwide.Since the COVID-19 pandemic began,many studies have focused on the impact of the disease on conditions such as diabetes,cardiovascular disease,pulmonary disorders,and renal malfunction.However,few studies have focused on musculoskeletal disorders related to COVID-19 infection.In this review,we update the current knowledge on the coronavirus with special reference to its effects during and after the pandemic on musculoskeletal aliments,which may inform clinical practice.

Prevalence and Seroprevalence of Non-SARS Human Coronaviruses 229E and OC43 in East Tyrol/Austria

The recent SARS-CoV-2 pandemic renewed interest in other previously discovered human coronaviruses—the non-severe acute respiratory syndrome human coronavirus (non-SARS hCoVs) and this study is a starting point for a closer investigation of those. With the pandemic behind us we believe it to be important to also examine the current and past respiratory pathogen landscape in the patient population in our care. Therefore, 954 nasopharyngeal swabs of patients with respiratory diseases collected between October 2018 and March 2020 were tested against the pathogens Mycoplasma pneumoniae, Bordetella pertussis, Influenza A and virus, Human metapneumovirus, respiratory syncytial virus, Parainfluenza virus, human Adenovirus and Polyoma virus BK/JC. Swabs negative against these pathogens were further tested for OC43 and 229E by RT-qPCR. Human coronaviruses 229E and OC43 were proven as the causative agents in a considerable number of cases, confirmed by PCR. Overall, our results show that those two non-SARS hCoVs were responsible for 13.9% (11 of 79) of infections with flu-like symptoms of unknown etiology in the study area. In the subsequent seroprevalence study, it was shown that the seroprevalence rate of IgG antibodies against 229E and OC43 was over 50%, indicating that a big part of the population in our study area has been in contact with these non-SARS-CoVs and has built the specific humoral immune response accordingly.

Ambisense polarity of genome RNA of orthomyxoviruses and coronaviruses

Influenza viruses and coronaviruses have linear single-stranded RNA genomes with negative and positive sense polarities and genes encoded in viral genomes are expressed in these viruses as positive and negative genes,respectively.Here we consider a novel gene identified in viral genomes in opposite direction,as positive in influenza and negative in coronaviruses,suggesting an ambisense genome strategy for both virus families.Noteworthy,the identified novel genes colocolized in the same RNA regions of viral genomes,where the previously known opposite genes are encoded,a so-called ambisense stacking architecture of genes in virus genome.It seems likely,that ambisense gene stacking in influenza and coronavirus families significantly increases genetic potential and virus diversity to extend virus-host adaptation pathways in nature.These data imply that ambisense viruses may have a multivirion mechanism,like"a dark side of the Moon",allowing production of the heterogeneous population of virions expressed through positive and negative sense genome strategies.

Decoding bovine coronavirus immune targets:an epitope informatics approach

Bovine coronavirus(BCoV)poses a significant threat to the global cattle industry,causing both respiratory and gastrointestinal infections in cattle populations.This necessitates the development of efficacious vaccines.While several inactivated and live BCoV vaccines exist,they are predominantly limited to calves.The immunization of adult cattle is imperative for BCoV infection control,as it curtails viral transmission to calves and ameliorates the impact of enteric and respiratory ailments across all age groups within the herd.This study presents an in silico methodology for devising a multiepitope vaccine targeting BCoV.The spike glycoprotein(S)and nucleocapsid(N)proteins,which are integral elements of the BCoV structure,play pivotal roles in the viral infection cycle and immune response.We constructed a remarkably effective multiepitope vaccine candidate specifically designed to combat the BCoV population.Using immunoinformatics technology,B-cell and T-cell epitopes were predicted and linked together using linkers and adjuvants to efficiently trigger both cellular and humoral immune responses in cattle.The in silico construct was characterized,and assessment of its physicochemical properties revealed the formation of a stable vaccine construct.After 3D modeling of the vaccine construct,molecular docking revealed a stable interaction with the bovine receptor bTLR4.Moreover,the viability of the vaccine’s high expression and simple purification was demonstrated by codon optimization and in silico cloning expression into the pET28a(+)vector.By applying immunoinformatics approaches,researchers aim to better understand the immune response to bovine coronavirus,discover potential targets for intervention,and facilitate the development of diagnostic tools and vaccines to mitigate the impact of this virus on cattle health and the livestock industry.We anticipate that the design will be useful as a preventive treatment for BCoV sickness in cattle,opening the door for further laboratory studies.

Efficacy and Safety of Lianhua Qingke Tablets in the Treatment of Long Coronavirus Disease (COVID) Cough: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study

Lianhua Qingke tablets,a patented traditional Chinese medicine that has validated clinical efficacy for treating cough caused by severe acute respiratory syndrome coronavirus 2 infection,lack rigorous evidence-based research evaluating their effect on long coronavirus disease(COVID)cough.A randomized,double-blind,placebo-controlled,multicenter clinical study was conducted among patients with long COVID cough from 19 hospitals and 23 community health centers in China.Patients were randomized 1:1 to receive either Lianhua Qingke tablets or placebo orally for 14 days(four tablets,1.84 g,three times a day).The primary endpoint indicator was the disappearance of cough,with the remission of cough also considered.Among 482 randomized patients,480(full analysis set 480;per-protocol set 470;safety set 480)were included in the primary analysis.According to the full analysis,the time until cough disappearance was significantly shorter in the trial group than in the control group,with a significant increase in the 14-day cough disappearance rate.Accordingly,the time to cough remission was significantly shorter in the trial group than in the control group.The change in the total symptom score was significantly greater in the trial group than in the control group on days 7 and 14,consistent with the results indicated by the visual analog scale(VAS)and cough evaluation test(CET)scores.No serious adverse events were recorded during the study.Lianhua Qingke tablets significantly improved the clinical symptoms of patients with long COVID cough.

The potential role of Gegen Qinlian decoction in the treatment of coronavirus disease 2019 based on network pharmacology and validation of lipopolysaccharide-induced macrophages

Background:Coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2,which has led to deaths and currently lacks an efficient treatment.Despite studies suggesting the potential of the Gegen Qinlian decoction(GQD)in preventing COVID-19,comprehensive analyses of its anti-COVID-19 potential are still lacking.Methods:GQD treatment was evaluated for its efficacy in ameliorating the early stage(24 hours)of lipopolysaccharide(LPS)-induced cytokine storm in vivo.Additionally,target genes of GQD were co-analyzed with COVID-19 signature genes to identify key ingredients and their pathways.Validation was also conducted using an LPS-induced macrophage model.Results:GQD treatment effectively ameliorated the early stage of LPS-induced cytokine storm in vivo.Key ingredients such as quercetin were found to be involved in multiple pathways,including inflammation,immunity,oxidative stress,cell proliferation,and apoptosis,through the AGE-RAGE signaling pathway and IL-17 signaling pathway.In the LPS-induced macrophage model,quercetin inhibited macrophage polarization(M1)and the secretion of inflammatory factors(IL-6,TNF-α,IL-17A).Conclusions:Our results indicate that GQD can be utilized in the treatment of cytokine storm induced by COVID-19 and has the potential to treat COVID-19 by suppressing the COVID-19 signature genes and macrophage polarization.

Impact of non-alcoholic fatty liver disease on coronavirus disease 2019: A systematic review

BACKGROUND Many studies have revealed a link between non-alcoholic fatty liver disease(NA-FLD)and coronavirus disease 2019(COVID-19),making understanding the relationship between these two conditions an absolute requirement.AIM To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD.METHODS This systematic review was conducted in accordance with the guidelines pro-vided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population,intervention,comparison,and outcome framework.The search strategy was run on three separate databases,PubMed/MEDLINE,Scopus,and Cochrane Central,which were systematically searched from inception until March 2024 to select all relevant studies.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched to identify grey literature.RESULTS After retrieval of 11 studies,a total of 39282 patients data were pooled.Mortality was found in 11.5%and 9.4%of people in NAFLD and non-NAFLD groups.In all,23.2%of NAFLD patients and 22%of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit,with days of stay varying.Ventilatory support ranged from 5%to 40.5%in the NAFLD cohort and from 3.1%to 20%in the non-NAFLD cohort.The incidence of acute liver injury showed significance.Clinical improvement on days 7 and 14 between the two classifications was significant.Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively,with 73.3%and 76.3%of patients being discharged.Readmission rates varied.CONCLUSION Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19.Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.

Clinical Effect of Yinhuang Qingfei Capsules in Treatment of Asymptomatic and Mild/Common Severe Acute Respiratory Syndrome Coronavirus 2 Infection:An Analysis of 242 Cases

[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.

Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.