Human Pandemic Research Articles

Phylogenetic Characterization of Novel Reassortant 2.3.4.4b H5N8 Highly Pathogenic Avian Influenza Viruses Isolated from Domestic Ducks in Egypt During the Winter Season 2021–2022

Avian influenza (AI) is an extremely contagious viral disease of domestic and wild birds that can spread rapidly among bird populations, inducing serious economic losses in the poultry industry. During the winter season 2021–2022, we isolated seventeen highly pathogenic avian influenza (HPAI) H5N8 viruses from outbreaks involving ducks in Egypt, occurring in both backyard and farm settings. The aim of this study was to pinpoint genetic key substitutions (KSs) that could heighten the risk of a human pandemic by influencing the virus’s virulence, replication ability, host specificity, susceptibility to drugs, or transmissibility. To understand their evolution, origin, and potential risks for a human pandemic, whole-genome sequencing and phylogenetic analysis were conducted. Our analysis identified numerous distinctive mutations in the Egyptian H5N8 viruses, suggesting potential enhancements in virulence, resistance to antiviral drugs, and facilitation of transmission in mammals. In this study, at least five genotypes within one genome constellation of H5N8 viruses were identified, raising concerns about the potential emergence of novel viruses with altered characteristics through reassortment between different genotypes and distinct groups. These findings underscore the role of ducks in the virus’s evolutionary process and emphasize the urgent need for enhanced biosecurity measures in domestic duck farms to mitigate pandemic risk.

Discriminating North American Swine Influenza Viruses with a Portable, One-Step, Triplex Real-Time RT-PCR Assay, and Portable Sequencing.

Swine harbors a genetically diverse population of swine influenza A viruses (IAV-S), with demonstrated potential to transmit to the human population, causing outbreaks and pandemics. Here, we describe the development of a one-step, triplex real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay that detects and distinguishes the majority of the antigenically distinct influenza A virus hemagglutinin (HA) clades currently circulating in North American swine, including the IAV-S H1 1A.1 (α), 1A.2 (β), 1A.3 (γ), 1B.2.2 (δ1) and 1B.2.1 (δ2) clades, and the IAV-S H3 2010.1 clade. We performed an in-field test at an exhibition swine show using in-field viral concentration and RNA extraction methodologies and a portable real-time PCR instrument, and rapidly identified three distinct IAV-S clades circulating within the N.A. swine population. Portable sequencing is used to further confirm the results of the in-field test of the swine triplex assay. The IAV-S triplex rRT-PCR assay can be easily transported and used in-field to characterize circulating IAV-S clades in North America, allowing for surveillance and early detection of North American IAV-S with human outbreak and pandemic potential.

Two phylogenetic cohorts of the nucleocapsid protein NP and their correlation with the host range of influenza A viruses

Influenza A virus has a wide natural areal among birds, mammals and humans. One of the main regulatory adaptors of the virus host range is the major NP protein of the viral nucleocapsid. Phylogenetic analysis of the NP protein of different viruses has revealed the existence of two phylogenetic cohorts in human influenza virus population. Cohort I includes classical human viruses that caused epidemics in 1957, 1968, 1977. Cohort II includes the H1N1/2009pdm virus, which had a mixed avian-swine origin, but caused global human pandemic. Also, the highly virulent H5N1 avian influenza virus emerged in 2021 and caused outbreaks of lethal infections in mammals, including humans, appeared to have the NP gene of the second phylogenetic cohort and, therefore, by the type of adaptation to human is similar to the H1N1/2009pdm virus and seems to possess a high epidemic potential for humans. The data obtained shed light on pathways and dynamics of avian influenza viruses adaptation to humans and propose phylogenetic algorithm for systemic monitoring of dangerous virus strains to predict epidemic harbingers and take immediate preventive measures.

Complex Evolutionary Dynamics of H5N8 Influenza A Viruses Revealed by Comprehensive Reassortment Analysis.

Influenza A viruses (IAVs) circulate among different species and have the potential to cause significant pandemics in humans. This study focuses on reassortment events in the H5N8 subtype of IAV, which poses a serious threat to public health due to its high pathogenicity in birds and potential for cross-species transmission. We retrieved 2359 H5N8 IAV sequences from GISAID, and filtered and analyzed 442 complete genomic sequences for reassortment events using pairwise distance deviation matrices (PDDMs) and pairwise distance correspondence plots (PDCPs). This detailed case study of specific H5N8 viruses revealed previously undescribed reassortment events, highlighting the complex evolutionary history and potential pandemic threat of H5N8 IAVs.

Reproductive health rights: a bibliometric analysis of childbirth

Purpose Reproductive health rights became an issue of interest long before the 1990s. Several policies were created to guarantee reproductive health rights, including birth rights. Women have the right to give birth in a way that is respectful and free from obstetric violence. Policymaking must, of course, be based on empirical evidence, so it is necessary to map studies on human rights in the context of childbirth. This study aims to investigate the viewpoint on human rights during childbirth across time by using a bibliometric methodology. Design/methodology/approach Bibliometric analysis was conducted using the VOSviewer application. The analysis was sourced from 301 articles on human rights during delivery for the 1976–2023 period from the Scopus database. Findings The studies concerning reproductive health rights encompass various topics, including reproductive health policy, human rights during childbirth, child marriage and human rights, pandemics and health care related to human rights. Research limitations/implications Studies related to human rights in reproductive health (especially childbirth) must be increased. Remember, policymaking must be based on the evidence found. Apart from that, empirical information about harmful actions during childbirth must be revealed so that it becomes a concern. While there has been a significant increase in the establishment of human rights during childbirth, there is a lack of research on this topic specifically in the Asian context. Researchers might consider this to be a matter of concern, given the implications for human rights. Two themes that have citations but a small number relate to obstetric violence and respectful maternity care during childbirth, so this could be a concern for other researchers for further studies. Originality/value This paper provides an overview of the most cited topics of human rights during childbirth, contributions by the distribution of studies throughout time, distribution of studies by country, the highest number of publications and citations.

Large-Scale Serological Survey of Influenza A Virus in South Korean Wild Boar (Sus scrofa).

In this comprehensive large-scale study, conducted from 2015 to 2019, 7,209 wild boars across South Korea were sampled to assess their exposure to influenza A viruses (IAVs). Of these, 250 (3.5%) were found to be IAV-positive by ELISA, and 150 (2.1%) by the hemagglutination inhibition test. Detected subtypes included 23 cases of pandemic 2009 H1N1, six of human seasonal H3N2, three of classical swine H1N1, 13 of triple-reassortant swine H1N2, seven of triple-reassortant swine H3N2, and seven of swine-origin H3N2 variant. Notably, none of the serum samples tested positive for avian IAV subtypes H3N8, H5N3, H7N7, and H9N2 or canine IAV subtype H3N2. This serologic analysis confirmed the exposure of Korean wild boars to various subtypes of swine and human influenza viruses, with some serum samples cross-reacting between swine and human strains, indicating potential infections with multiple IAVs. The results highlight the potential of wild boar as a novel mixing vessel, facilitating the adaptation of IAVs and their spillover to other hosts, including humans. In light of these findings, we recommend regular and frequent surveillance of circulating influenza viruses in the wild boar population as a proactive measure to prevent potential human influenza pandemics and wild boar influenza epizootics.

Towards the Development of a Cream with Antiviral Properties Targeting Both the Influenza A Virus and SARS-CoV-2

Objective: Many severe acute respiratory infections are caused by viral pathogens, and viruses are responsible for a large number of deaths worldwide. Among the most common respiratory viruses are the influenza A virus (IAV) and, more recently, the SARS-CoV-2 that emerged in 2019 and caused the most significant human pandemic of the beginning of the 21st century. Both IAV and SARS-CoV-2 share clinical features and a common transmission route through the emission of viral particles via aerosols and droplets. These penetrate the host after entry from the nose and mouth or an indirect mode of transmission via contact contamination of different media. These facts prompted us to investigate the possibility of designing a soft cream with a virucidal activity targeted against IAV and SARS-CoV-2. Methods: We first investigated the action of chemical compounds known to have antiviral properties such as cyclodextrin, or algae extracts containing sulfated polysaccharides, on cultured cells infected with lentiviral viral particles pseudotyped (VP) with either proteins HA (hemagglutinin) and NA (neuraminidase) from IAV or the G protein from the vesicular stomatitis virus or spike-bearing particles in order to select molecules with antiviral activities in human embryonic kidney (HEK293T) cells. Results: Our results show that some cyclodextrin-containing creams can significantly reduce the stability of HANA- and spike-bearing particles when they are applied prior to challenge with a viral inoculum on skin. Conclusions: We observed some specificities of these creams towards either IAV or SARS-CoV-2, indicating that the neutralization of viral activity is correlated with the mechanism of receptor interaction and entry of these two pathogens.

Yersinia pestis can infect the Pawlowsky glands of human body lice and be transmitted by louse bite.

Yersinia pestis, the causative agent of plague, is a highly lethal vector-borne pathogen responsible for killing large portions of Europe's population during the Black Death of the Middle Ages. In the wild, Y. pestis cycles between fleas and rodents; occasionally spilling over into humans bitten by infectious fleas. For this reason, fleas and the rats harboring them have been considered the main epidemiological drivers of previous plague pandemics. Human ectoparasites, such as the body louse (Pediculus humanus humanus), have largely been discounted due to their reputation as inefficient vectors of plague bacilli. Using a membrane-feeder adapted strain of body lice, we show that the digestive tract of some body lice become chronically infected with Y. pestis at bacteremia as low as 1 × 105 CFU/ml, and these lice routinely defecate Y. pestis. At higher bacteremia (≥1 × 107 CFU/ml), a subset of the lice develop an infection within the Pawlowsky glands (PGs), a pair of putative accessory salivary glands in the louse head. Lice that developed PG infection transmitted Y. pestis more consistently than those with bacteria only in the digestive tract. These glands are thought to secrete lubricant onto the mouthparts, and we hypothesize that when infected, their secretions contaminate the mouthparts prior to feeding, resulting in bite-based transmission of Y. pestis. The body louse's high level of susceptibility to infection by gram-negative bacteria and their potential to transmit plague bacilli by multiple mechanisms supports the hypothesis that they may have played a role in previous human plague pandemics and local outbreaks.

Molecular characterization of the whole genome of H9N2 avian influenza virus isolated from Egyptian poultry farms

H9N2 avian influenza viruses (AIVs) affect both poultry and humans on a global level, and they are especially prevalent in Egypt. In this study, we sequenced the entire genome of AIV H9N2 isolated from chickens in Egypt in 2021, using next-generation sequencing (NGS) technology. Phylogenetic analysis of the resulting sequences showed that the studied strain was generally monophyletic and grouped within the G1 sublineage of the Eurasian lineage. Four segments (polymerase basic 2 [PB2], polymerase basic 1 [PB1], polymerase acidic [PA], and non-structural [NS]) were related to Egyptian genotype II, while the nucleoprotein (NP), neuraminidase (NA), matrix (M), and haemagglutinin (HA) segments were related to Egyptian genotype I. Molecular analysis revealed that HA protein contained amino acid residues (191H and 234L) that suggested a predilection for attaching to human-like receptors. The antigenic sites of HA had two nonsynonymous mutations: V194I at antigenic site A and M40K at antigenic site B. Furthermore, the R403W and S372A mutations, which have been observed in H3N2 and H2N2 strains that caused human pandemics, were found in the NA protein of the detected strain. The internal proteins contained virulence markers: 504V in the PB2 protein, 622G, 436Y, 207K, and 677T in the PB1 protein, 127V, 550L, and 672L in PA protein, and 64F and 69P in the M protein. These results show that the detected strain had undergone intrasubtype reassortment. Furthermore, it contains changes in the viral proteins that make it more likely to be virulent, raising a question about the tendency of AIV H9N2 to become highly pathogenic in the future for both poultry and humans.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.

Two Phylogenetic Cohorts of the Nucleocapsid Protein NP and Their Correlation with the Host Range of Influenza A Viruses.

Influenza A virus has a wide natural areal among birds, mammals, and humans. One of the main regulatory adaptors of the virus host range is the major NP protein of the viral nucleocapsid. Phylogenetic analysis of the NP protein of different viruses has revealed the existence of two phylogenetic cohorts in human influenza virus population. Cohort I includes classical human viruses that caused epidemics in 1957, 1968, 1977. Cohort II includes the H1N1/2009pdm virus, which had a mixed avian-swine origin but caused global human pandemic. Also, the highly virulent H5N1 avian influenza virus emerged in 2021 and caused outbreaks of lethal infections in mammals including humans, appeared to have the NP gene of the second phylogenetic cohort and, therefore, by the type of adaptation to human is similar to the H1N1/2009pdm virus and seems to possess a high epidemic potential for humans. The data obtained shed light on pathways and dynamics of adaptation of avian influenza viruses to humans and propose phylogenetic algorithm for systemic monitoring of dangerous virus strains to predict epidemic harbingers and take immediate preventive measures.

Safety and immunogenicity of COVID-19 vaccine ZF2001 in Chinese aged 60 years and older

Coronavirus disease 2019 (COVID-19) is still causing ongoing human pandemic. Older adults are the population at high risk of developing severe COVID-19 or death. ZF2001, a protein subunit vaccine comprising two copies of tandem receptor-binding domain (RBD), has demonstrated safety and immunogenicity in population aged 3-17 and 18-59 after three doses of vaccination. Moreover, it has shown efficacy in the prevention of symptomatic COVID-19 after a six-month follow-up for adults beyond 18 years of age in a phase 3 trial. However, its immunogenicity in individuals 60 years of age and older has not been reported and needs further investigation. Here, we evaluated the safety and immunogenicity of ZF2001 in this older age group. All adverse events were grade 1 and 2 (11/20 participants in the 25 μg group; 12/20 participants in the 50 μg group; 4/10 participants in the placebo group). No serious adverse events were considered relevant to the investigational products. The seroconversion rate for neutralizing antibody against SARS-CoV-2 prototype live virus was approximately 95% on day 30 after the third dose, and it remained above 75% after half a year. However, those serum samples exhibited limited neutralization capabilities against the omicron BA.4/5 and XBB.1.16 pseudoviruses, highlighting the urgent need to develop next-generation COVID-19 vaccines.

Genetic characterization of influenza A(H1N1)pdm09 virus in 2023 in Huzhou, China

IntroductionSince its identification in April 2009, influenza A(H1N1)pdm09 virus has continued to cause significant outbreaks of respiratory tract infections, including pandemics in humans. In the course of its evolution, the virus has acquired many mutations that cause increased disease severity. Regular molecular surveillance of the virus is essential to mark the evolutionary changes that may cause a shift in viral behavior. MethodsTwenty-five (H1N1)pdm09 isolates from Huzhou, China, in 2023 were randomly selected for whole-genome sequencing along with analysis of nucleotide and amino acid sequence identity, average genetic distance, antigen variation sites, receptor binding sites, pathogenicity, potential glycosylation sites, and drug resistance gene sites. ResultsThe 25 (H1N1)pdm09 strains and representative 2023–2024 northern hemisphere vaccine strain A/Wisconsin/67/2022 showed nucleotide and amino acid similarity of 98.41 %–99.22 % and 98.41 %–99.36 %, respectively. This virus belongs to the 6B1A.5a.2a evolutionary lineage. There were 19 amino acid variations in hemagglutinin (HA) protein. Substitutions S137P and R142K occurred in the epitope Ca2 cluster. A total of 13 amino acids were mutated in neuraminidase (NA) protein, and 9 key protease active sites and amino acid sites related to NA inhibitor (NAI) resistance were not mutated. Five amino acid sites of matrix-2 (M2) protein associated with drug resistance were not replaced, but amino acid 31 of M2 protein was shown to be N in the 2023 pandemic strain (H1N1)pdm09 and vaccine strain A/Wisconsin/67/2022. There were seven and eight potential glycosylation sites for HA protein and NA protein, respectively. Compared with the vaccine strains, there were no new or missing potential glycosylation sites in the 25 (H1N1)pdm09 influenza virus isolates. No multiple continuous alkaline amino acids were found in the HA cleavage site of the 25 isolates. ConclusionsThe recommended vaccine strain A/Wisconsin/67/2022 has good prevention potential against the current circulating influenza (H1N1)pdm09. At present, NAIs have good therapeutic and preventive effects against (H1N1)pdm09 circulating in Huzhou, China, but the virus is naturally resistant to amantadines. At present, the (H1N1)pdm09 strain circulating in Huzhou, China, is characterized by low pathogenicity. However, regular molecular surveillance of (H1N1)pdm09 is important to monitor the behavior of the virus in terms of increases in virulence, drug resistance, and emergence of novel strains.

Conserved structures and dynamics in 5'-proximal regions of Betacoronavirus RNA genomes.

Betacoronaviruses are a genus within the Coronaviridae family of RNA viruses. They are capable of infecting vertebrates and causing epidemics as well as global pandemics in humans. Mitigating the threat posed by Betacoronaviruses requires an understanding of their molecular diversity. The development of novel antivirals hinges on understanding the key regulatory elements within the viral RNA genomes, in particular the 5'-proximal region, which is pivotal for viral protein synthesis. Using a combination of cryo-electron microscopy, atomic force microscopy, chemical probing, and computational modeling, we determined the structures of 5'-proximal regions in RNA genomes of Betacoronaviruses from four subgenera: OC43-CoV, SARS-CoV-2, MERS-CoV, and Rousettus bat-CoV. We obtained cryo-electron microscopy maps and determined atomic-resolution models for the stem-loop-5 (SL5) region at the translation start site and found that despite low sequence similarity and variable length of the helical elements it exhibits a remarkable structural conservation. Atomic force microscopy imaging revealed a common domain organization and a dynamic arrangement of structural elements connected with flexible linkers across all four Betacoronavirus subgenera. Together, these results reveal common features of a critical regulatory region shared between different Betacoronavirus RNA genomes, which may allow targeting of these RNAs by broad-spectrum antiviral therapeutics.

Agriculture evolution, sustainability and trends, focusing on Brazilian agribusiness: a review

The world’s population is expected to grow by 30%–35% over the next 60 years. Forecasts indicate that the world’s population will reach almost 10 billion by 2050, with India and China as the most populous countries. As a result, the demand for global food production, particularly protein and dairy products, and their nutritional quality will need to increase by 50%–75%. In addition to increasing food production, it is also necessary to consider and reduce the impact on the environment and ecosystem. On the one hand, the threat of climate change, the reduction of arable land for agricultural expansion, the economic impact of geopolitical conflicts, the human and animal health pandemics, the conjuncture of the domestic political environments, and the demand for new technologies are the main bottlenecks to increasing sustainable food production worldwide. In contrast, notable technological advances have been achieved in current agriculture through basic and advanced scientific research, development, innovation, and technology transfer to the agribusiness sector. Technological advances in various sectors will become increasingly important to increase food production and minimize environmental impacts. This review study briefly highlights the major technological advances in world agriculture that have contributed to the substantial increase in food production from the early days of extractive agriculture to high-performance agriculture. It then highlights the key breakthroughs, disruptive technologies, the impact of climate change on agriculture, and contributions from molecular sciences that are revolutionizing global agriculture, focusing on Brazilian agriculture, livestock, and agribusiness. Subsequently, the evolution of Brazilian agriculture is highlighted based on the market share of agricultural products and its relevance to the national GDP. Finally, the potential decision-making that could have a positive impact on the Brazilian agribusiness sector and that will affect the import and export of agribusiness products were addressed. Therefore, the importance of supporting the agribusiness sector to increase healthy food production with higher nutritional quality and with less impact on the environment and human life was highlighted.

Zoonosis and zooanthroponosis of emerging respiratory viruses.

Lung infections in Influenza-Like Illness (ILI) are triggered by a variety of respiratory viruses. All human pandemics have been caused by the members of two major virus families, namely Orthomyxoviridae (influenza A viruses (IAVs); subtypes H1N1, H2N2, and H3N2) and Coronaviridae (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). These viruses acquired some adaptive changes in a known intermediate host including domestic birds (IAVs) or unknown intermediate host (SARS-CoV-2) following transmission from their natural reservoirs (e.g. migratory birds or bats, respectively). Verily, these acquired adaptive substitutions facilitated crossing species barriers by these viruses to infect humans in a phenomenon that is known as zoonosis. Besides, these adaptive substitutions aided the variant strain to transmit horizontally to other contact non-human animal species including pets and wild animals (zooanthroponosis). Herein we discuss the main zoonotic and reverse-zoonosis events that occurred during the last two pandemics of influenza A/H1N1 and SARS-CoV-2. We also highlight the impact of interspecies transmission of these pandemic viruses on virus evolution and possible prophylactic and therapeutic interventions. Based on information available and presented in this review article, it is important to close monitoring viral zoonosis and viral reverse zoonosis of pandemic strains within a One-Health and One-World approach to mitigate their unforeseen risks, such as virus evolution and resistance to limited prophylactic and therapeutic interventions.

Lack of detection of SARS-CoV-2 in wildlife from Kerala, India in 2020-21.

Spillover of SARS-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white-tailed deer in North America and increasing divergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121 Rhinolophus rouxii (Rufous Horsehoe Bat), six Rhinolophus bedommei (Lesser Woolly Horseshoe Bat), 15 Rossettus leschenaultii (Fulvous Fruit Bat), 47 Macaca radiata (Bonnet macaques), 35 Paradoxurus hermaphroditus (Common Palm Civet), five Viverricula indica (Small Indian Civet), four Herpestes edwardsii (Common Mongoose), ten Panthera tigris (Bengal Tiger), eight Panthera pardus fusca (Indian Leopard), four Prionailurus bengalensis (Leopard cats), two Felis chaus (Jungle cats), two Cuon alpinus (Wild dogs) and one Melursus ursinus (sloth bear).

The generation of hemagglutinin monoclonal antibodies against H9N2 influenza virus

H9N2 avian influenza viruses (AIVs) are widely distributed, causing continuous outbreaks in poultry and sporadic infections in humans. Vaccination is the primary method used to prevent and control H9N2 AIV infection. However, the ongoing evolution and mutation of AIVs often result in limited protection effects from vaccines. Therapeutic monoclonal antibodies (mAbs) targeting influenza viruses offer a promising alternative. In this study, we immunized mice with inactivated H9N2-W1 virus, and we screened and acquired five mAbs, namely 4D12, F4, 5C8, 2G8 and A11. We showed that all five mAbs specifically targeted the HA protein of various H9N2 AIV strains. In vitro neutralization tests demonstrated that all five mAbs exhibited neutralization activity against H9N2 AIVs, with mAb F4 displaying the most potent neutralization effect. The F4 mAb exhibited dose-dependent preventive and therapeutic effects against lethal H9N2-115 infection, and the administration of F4 at a dose of 3 μg/g provided complete protection in vivo. Our study presents an alternative approach for preventing and controlling H9N2 AIV infection. Furthermore, the identified F4 mAb holds promise as a solution to potential pandemics in humans caused by H9N2 AIVs.

Mutational antigenic landscape of prevailing H9N2 influenza virus hemagglutinin spectrum

H9N2 influenza viruses are globally endemic in birds, and a sharp increase in human infections with H9N2 occurred during 2021 to 2022. In this study, we assess the antigenic and pathogenic impact of 23 hemagglutinin (HA) amino acid mutations. Our study reveals that three specific mutations, labeled R164Q, N166D, and I220T, are responsible for the binding of antibodies with escape mutations. Variants containing R164Q and I220T mutations increase viral replication in avian and mammalian cells. Furthermore, T150A and I220T mutations are found to enhance viral replication in mice, indicating that these mutations may have the potential to adapt mammals. Structure analysis reveals that residues 164 and 220 bearing R164Q and I220T mutations increase interactions with the surrounding residues. Our findings enrich current knowledge about the risk assessment regarding which predominant HA immune-escape mutations of H9N2 viruses may pose the greatest threat to the emergence of pandemics in birds and humans.

PULMONARY REHABILITATION IN POST COVID SEQUELAE IN INDIA

An outbreak of pneumonia was reported in Wuhan, Hubei Province, China in December 2019 and quickly spread to all Chinese provinces. 1, 2 The coronavirus disease (COVID-19) pandemic spread through 190 countries within 20 weeks from Wuhan, China, affecting 334,000 populations. This caused more than 14,500 deaths by mid-March 2020. The number of infected people has risen to 1,210,956 in the month of April 6, 2020, with 67,594 associated expirations. 4 India recorded its first COVID-19 infection case on January 30, 2020 in a student from China's capital, Wuhan. In 2020, India reported 360 positive COVID-19 cases from 23 states across the country. 4 in India, the number of asymptomatic cases was higher. On April 4, 2019, a novel coronavirus pathogen was proved to be a novel betacoronavirus. 2 Sub-micron sized viruses, narrated as "organisms at the edge of life", are liable for some of the worst human pandemics in history, like influenza (1918), smallpox (1978), and COVID-19, as of September 17, 2020. 2 The SARS-CoV-2 virus is causative for COVID-19. Nearly 29 million people have been affected by this virus, which caused 936,521 deaths worldwide (WHO, 2020). 2 Corona viruses are single-stranded positive-strand RNA viruses that are known to contain some of the largest viral genomes, up to around 32 kbp in length. Following an augmentation in the number of coronavirus genome sequences available and following efforts to investigate the diversity in the wild, the family Corona viridae now contains four genera. The structure of the coronavirus as given in figure 1 Those species that belong to the genera Alpha corona virus and Beta corona virus can infect mammalian hosts, while those of Gamma corona virus and the recently defined Delta corona virus mainly infect avian species. 3 The highly pathogenic human coronaviruses, Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), belong to lineage B (sub-genus Sarbecovirus) and lineage C (sub-genus Merbecovirus) of Betacoronavirus. 3