Emerging porcine Enterovirus G infections, epidemiological, complete genome sequencing, evolutionary and risk factor analysis in India.

The current study reports the in-depth analysis of the epidemiology, risk factors, and molecular characterization of a complete genome of Enterovirus G (EV-G) isolated from Indian pigs. We analysed several genes of EV-G isolates collected from various provinces in India, using phylogenetic analysis, recombination detection, SimPlot, and selection pressure analyses. Our analysis of 534 porcine faecal samples revealed that 11.61% (62/534) of the samples were positive for EV-G. While the G6 genotype was the most predominant, our findings showed that Indian EV-G strains also clustered with EV-G types G1, G6, G8, and G9. Furthermore, Indian EV-G strains exhibited the highest nucleotide similarity with Vietnamese (81.3%) and Chinese EV-G isolates (80.3%). Moreover, we identified a recombinant Indian EV-G strain with a putative origin from a Japanese isolate and South Korean EV-G isolate. In summary, our findings provide significant insights into the epidemiology, genetic diversity, and evolution of EV-G in India.

KOBUVIRUS DETECTION IN THE CRITICALLY ENDANGERED PYGMY HOG (PORCULA SALVANIA), INDIA.

Pygmy hogs (Porcula salvania) are the smallest and rarest wild suid. It is categorized as a Critically Endangered species as per the Red List of the International Union for Conservation of Nature. This study reports the first detection of a single-stranded RNA virus species, Aichivirus C, belonging to the genus Kobuvirus (KobV) and the family Picornaviridae, in pygmy hogs. KobV species are identified as a cause of acute gastroenteritis among children in India. As of now, there exists no report on the detection of KobV in animals from India. We used a detection assay based on reverse transcription-polymerase chain reaction for KobV screening in pygmy hogs from a conservation center in India. The 3D polymerase gene-based molecular analysis revealed KobV presence in the Indian wild suid, pygmy hogs. Of the 15 samples tested, three were found positive for picornaviruses and were negative for rotavirus A, rotavirus C, astrovirus, picobirnavirus and caliciviruses. Nucleotide-based sequence analysis of the partial 3D polymerase gene revealed close identity with porcine KobV from the Czech Republic (JX232619, 90.6%-91.6%) and Hungary (NC_011829, 89.8%-91.6%), wherein one of the current study strains clustered with the Czech Republic JX232619 strain in the phylogenetic tree. Further investigation of the role of KobV in health and disease of pygmy hogs is warranted.

How artificial intelligence may help the Covid-19 pandemic: Pitfalls and lessons for the future.

The clinical severity, rapid transmission and human losses due to coronavirus disease 2019 (Covid-19) have led the World Health Organization to declare it a pandemic. Traditional epidemiological tools are being significantly complemented by recent innovations especially using artificial intelligence (AI) and machine learning. AI-based model systems could improve pattern recognition of disease spread in populations and predictions of outbreaks in different geographical locations. A variable and a minimal amount of data are available for the signs and symptoms of Covid-19, allowing a composite of maximum likelihood algorithms to be employed to enhance the accuracy of disease diagnosis and to identify potential drugs. AI-based forecasting and predictions are expected to complement traditional approaches by helping public health officials to select better response and preparedness measures against Covid-19 cases. AI-based approaches have helped address the key issues but a significant impact on the global healthcare industry is yet to be achieved. The capability of AI to address the challenges may make it a key player in the operation of healthcare systems in future. Here, we present an overview of the prospective applications of the AI model systems in healthcare settings during the ongoing Covid-19 pandemic.

BCG vaccine: a hope to control COVID-19 pandemic amid crisis.

COVID-19 caused by the virus SARS-CoV-2 has gripped essentially all countries in the world, and has infected millions and killed hundreds of thousands of people. Several innovative approaches are in development to restrain the spread of SARS-CoV-2. In particular, BCG, a vaccine against tuberculosis (TB), is being considered as an alternative therapeutic modality. BCG vaccine is known to induce both humoral and adaptive immunities, thereby activating both nonspecific and cross-reactive immune responses in the host, which combined could effectively resist other pathogens including SARS-CoV-2. Notably, some studies have revealed that SARS-CoV-2 infectivity, case positivity, and mortality rate have been higher in countries that have not adopted BCG vaccination than in countries that have done so. This review presents an overview of the concepts underlying BCG vaccination and its nonspecific immuological effects and protection, resulting in 'trained immunity' and potential utility for resisting COVID-19.

Coronavirus Disease Pandemic (COVID-19): Challenges and a Global Perspective.

The technology-driven world of the 21st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2') within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures.

Coronavirus Disease 2019-COVID-19.

SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.

Classical Swine Fever Virus Biology, Clinicopathology, Diagnosis, Vaccines and a Meta-Analysis of Prevalence: A Review from the Indian Perspective.

: Classical swine fever (CSF) is an economically significant, multi-systemic, highly contagious viral disease of swine world over. The disease is notifiable to the World Organization for Animal Health (OIE) due to its enormous consequences on porcine health and the pig industry. In India, the pig population is 9.06 million and contributes around 1.7% of the total livestock population. The pig industry is not well organized and is mostly concentrated in the eastern and northeastern states of the country (~40% of the country's population). Since the first suspected CSF outbreak in India during 1944, a large number of outbreaks have been reported across the country, and CSF has acquired an endemic status. As of date, there is a scarcity of comprehensive information on CSF from India. Therefore, in this review, we undertook a systematic review to compile and evaluate the prevalence and genetic diversity of the CSF virus situation in the porcine population from India, targeting particular virus genes sequence analysis, published reports on prevalence, pathology, and updates on indigenous diagnostics and vaccines. The CSF virus (CSFV) is genetically diverse, and at least three phylogenetic groups are circulating throughout the world. In India, though genotype 1.1 predominates, recently published reports point toward increasing evidence of co-circulation of sub-genotype 2.2 followed by 2.1. Sequence identities and phylogenetic analysis of Indian CSFV reveal high genetic divergence among circulating strains. In the meta-analysis random-effects model, the estimated overall CSF prevalence was 35.4%, encompassing data from both antigen and antibody tests, and region-wise sub-group analysis indicated variable incidence from 25% in the southern to nearly 40% in the central zone, eastern, and northeastern regions. A country-wide immunization approach, along with other control measures, has been implemented to reduce the disease incidence and eliminate the virus in time to come.

Emerging novel coronavirus (2019-nCoV)-current scenario, evolutionary perspective based on genome analysis and recent developments.

Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade's first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as 'Public Health Emergency of International Concern' on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.

Genomic Analysis of an Indian G8P[1] Caprine Rotavirus-A Strain Revealing Artiodactyl and DS-1-Like Human Multispecies Reassortment.

The surveillance studies for the presence of caprine rotavirus A (RVA) are limited in India, and the data for the whole-genome analysis of the caprine RVA is not available. This study describes the whole-genome-based analysis of a caprine rotavirus A strain, RVA/Goat-wt/IND/K-98/2015, from a goat kid in India. The genomic analysis revealed that the caprine RVA strain K-98, possess artiodactyl-like and DS-1 human-like genome constellation G8P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3. The three structural genes (VP2, VP4, and VP7) were close to caprine host having nucleotide-based identity range between 97.5 and 98.9%. Apart from them, other gene segments showed similarity with either bovine or human like genes, ultimately pointing toward a common evolutionary origin having an artiodactyl-type backbone of strain K-98. Phylogenetically, the various genes of the current study isolate also clustered inside clades comprising Human-Bovine-Caprine isolates from worldwide. The current findings add to the knowledge on caprine rotaviruses and might play a substantial role in designing future vaccines or different alternative strategies combating such infections having public health significance. To the best of our knowledge, this is the first report on the whole-genome characterization of a caprine RVA G8P[1] strain from India. Concerning the complex nature of the K-98 genome, whole-genome analyses of more numbers of RVA strains from different parts of the country are needed to comprehend the genomic nature and genetic diversity among caprine RVA.

Species C Rotaviruses in Children with Diarrhea in India, 2010-2013: A Potentially Neglected Cause of Acute Gastroenteritis.

All over the world, children and adults are severely affected by acute gastroenteritis, caused by one of the emerging enteric pathogens, rotavirus C (RVC). At present, no extensive surveillance program is running for RVC in India, and its prevalence is largely unknown except cases of local outbreaks. Here, we intended to detect the presence of RVC in diarrheic children visiting or admitted to hospitals in Haldwani (state of Uttarakhand, India), a city located in the foothills of the Himalayas. During 2010-2013, we screened 119 samples for RVC by an RVC VP6 gene-specific RT-PCR. Of these, 38 (31.93%) were found positive, which is higher than the incidence rates reported so far from India. The phylogenetic analysis of the derived nucleotide sequences from one of the human RVC (HuRVC) isolates, designated as HuRVC/H28/2013/India, showed that the study isolate belongs to genotype I2, P2 and E2 for RVC structural genes 6 and 4 (VP6, and VP4) and non-structural gene 4 (NSP4), respectively. Furthermore, the VP6 gene of HuRVC/H28/2013/India shows the highest similarity to a recently-reported human-like porcine RVC (PoRVC/ASM140/2013/India, KT932963) from India suggesting zoonotic transmission. We also report a full-length NSP4 gene sequence of human RVC from India. Under the One-health platforms there is a need to launch combined human and animal RVC surveillance programs for a better understanding of the epidemiology of RVC infections and for implementing control strategies.Reoviridae, possess 11 double-stranded segments of RNA that encode six structural viral proteins (VP1, VP2, VP3, VP4, VP6, VP7) and five/six non-structural proteins (NSP1-NSP5/6) [7]. Based on the antigenic properties of the major inner capsid protein (VP6), RVs are subdivided into eight well-characterized species (A-H) and two putative species viz. I and J [8-10]. Humans and other mammalian species are affected by species A, B, C and H rotaviruses and birds by species D, F and G, and species E has been reported exclusively in pigs [7,8,11-17]. The newly-proposed species I is reported in dogs [18] and cats [19], whereas species J is found in bats [10].

Antigenic characterization of H5N1 highly pathogenic avian influenza viruses isolated from poultry in India, 2006-2015.

Highly pathogenic avian influenza (HPAI) is a major health concern worldwide. In this study, we focused on antigenic analysis of HPAI H5N1 viruses isolated from poultry in India between 2006 and 2015 comprising 25 isolates from four phylogenetic clades 2.2 (1 isolate), 2.2.2.1 (1 isolate), 2.3.2.1a (17 isolates) and 2.3.2.1c (6 isolates). Seven H5N1 isolates from all four clades were selected for production of chicken antiserum, and antigenic analysis was carried out by hemagglutination inhibition (HI) assay. HI data indicated antigenic divergence (6-21 fold reduction in cross-reactivity) between the two recently emerged clades 2.3.2.1a and 2.3.2.1c. These two clades are highly divergent (21-128 fold reduction in HI titre) from the earlier clades 2.2 /2.2.2.1 isolated in India. However, a maximum of 2-fold and 4-fold reduction in cross-reactivity was observed within the isolates of homologous clades 2.3.2.1c and 2.3.2.1a, respectively. The molecular basis of inter-clade antigenic divergence was examined in the haemagglutinin (HA) antigenic sites of the H5N1 virus. Amino acid changes at 8 HA antigenic sites were observed between clades 2.3.2.1a and 2.3.2.1c, whereas 20-23 substitutions were observed between clades 2.3.2.1a/2.3.2.1c and 2.2/2.2.2.1. Therefore, a systematic analysis of antigenic drift of the contemporary field isolates is a pre-requisite for determining the suitable strain(s) for vaccine candidature.